Efficient computation of absent words in genomic sequences

Herold J, Kurtz S, Giegerich R. Efficient computation of absent words in genomic sequences. BMC Bioinformatics. 2008;9(1): 167.Background: Analysis of sequence composition is a routine task in genome research. Organisms are characterized by their base composition, dinucleotide relative abundance, codon usage, and so on. Unique subsequences are markers of special interest in genome comparison, expression profiling, and genetic engineering. Relative to a random sequence of the same length, unique subsequences are overrepresented in real genomes. Shortest words absent from a genome have been addressed in two recent studies. Results: We describe a new algorithm and software for the computation of absent words. It is more efficient than previous algorithms and easier to use. It directly computes unwords without the need to specify a length estimate. Moreover, it avoids the space requirements of index structures such as suffix trees and suffix arrays. Our implementation is available as an open source package. We compute unwords of human and mouse as well as some other organisms, covering a genome size range from 109 down to 105 bp. Conclusion: The new algorithm computes absent words for the human genome in 10 minutes on standard hardware, using only 2.5 Mb of space. This enables us to perform this type of analysis not only for the largest genomes available so far, but also for the emerging pan- and meta-genome data

Bridging the gap:a review of dose investigations in paediatric investigation plans

Aims In the EU, development of new medicines for children should follow a prospectively agreed paediatric investigation plan (PIP). Finding the right dose for children is crucial but challenging due to the variability of pharmacokinetics across age groups and the limited sample sizes available. We examined strategies adopted in PIPs to support paediatric dosing recommendations to identify common assumptions underlying dose investigations and the attempts planned to verify them in children. Methods We extracted data from 73 PIP opinions recently adopted by the Paediatric Committee of the European Medicines Agency. These opinions represented 79 medicinal development programmes and comprised a total of 97 dose investigation studies. We identified the design of these dose investigation studies, recorded the analyses planned and determined the criteria used to define target doses. Results Most dose investigation studies are clinical trials (83 of 97) that evaluate a single dosing rule. Sample sizes used to investigate dose are highly variable across programmes, with smaller numbers used in younger children (< 2 years). Many studies (40 of 97) do not pre-specify a target dose criterion. Of those that do, most (33 of 57 studies) guide decisions using pharmacokinetic data alone. Conclusions Common assumptions underlying dose investigation strategies include dose proportionality and similar exposure−response relationships in adults and children. Few development programmes pre-specify steps to verify assumptions in children. There is scope for the use of Bayesian methods as a framework for synthesizing existing information to quantify prior uncertainty about assumptions. This process can inform the design of optimal drug development strategies

Re-expression of IGF-II is important for beta cell regeneration in adult mice

Background The key factors which support re-expansion of beta cell numbers after injury are largely unknown. Insulin-like growth factor II (IGF-II) plays a critical role in supporting cell division and differentiation during ontogeny but its role in the adult is not known. In this study we investigated the effect of IGF-II on beta cell regeneration. Methodology/Principal Findings We employed an in vivo model of ‘switchable’ c-Myc-induced beta cell ablation, pIns-c-MycERTAM, in which 90% of beta cells are lost following 11 days of c-Myc (Myc) activation in vivo. Importantly, such ablation is normally followed by beta cell regeneration once Myc is deactivated, enabling functional studies of beta cell regeneration in vivo. IGF-II was shown to be re-expressed in the adult pancreas of pIns-c-MycERTAM/IGF-II+/+ (MIG) mice, following beta cell injury. As expected in the presence of IGF-II beta cell mass and numbers recover rapidly after ablation. In contrast, in pIns-c-MycERTAM/IGF-II+/− (MIGKO) mice, which express no IGF-II, recovery of beta cell mass and numbers were delayed and impaired. Despite failure of beta cell number increase, MIGKO mice recovered from hyperglycaemia, although this was delayed. Conclusions/Significance Our results demonstrate that beta cell regeneration in adult mice depends on re-expression of IGF-II, and supports the utility of using such ablation-recovery models for identifying other potential factors critical for underpinning successful beta cell regeneration in vivo. The potential therapeutic benefits of manipulating the IGF-II signaling systems merit further exploration

Vertrauenprofessor*in – Ein neues Unterstützungsformat für den wissenschaftlichen Nachwuchs

Wir, als Sprecherinnen der GDM Nachwuchsvertretung, informieren über das neue Unterstützungsformat der Vertrauensprofessor*in. Damit möchten wir Doktorandinnen und Doktorandin in schwierigen Situationen unterstützen

Einleitung

Einleitung. Vielfalt und Integration – das sind die Schlagworte, in denen wir meinen, das Schaffen und Denken von Elisabeth Burr angemessen bündeln zu können. Ihr zu Ehren und anlässlich ihres Ausscheidens als ordentliches Mitglied einer Universität ist diese Festschrift entstanden, an der sich ehemalige und aktuelle Kolleginnen und Kollegen, Weggefährtinnen und Weggefährten, Schüler und Schülerinnen beteiligt haben

Gas Flow Shaping via Novel Modular Nozzle System (MoNoS) Augments kINPen-Mediated Toxicity and Immunogenicity in Tumor Organoids

Medical gas plasma is an experimental technology for anticancer therapy. Here, partial gas ionization yielded reactive oxygen and nitrogen species, placing the technique at the heart of applied redox biomedicine. Especially with the gas plasma jet kINPen, anti-tumor efficacy was demonstrated. This study aimed to examine the potential of using passive flow shaping to enhance the medical benefits of atmospheric plasma jets (APPJ). We used an in-house developed, proprietary Modular Nozzle System (MoNoS; patent-pending) to modify the flow properties of a kINPen. MoNoS increased the nominal plasma jet-derived reactive species deposition area and stabilized the air-plasma ratio within the active plasma zone while shielding it from external flow disturbances or gas impurities. At modest flow rates, dynamic pressure reduction (DPR) adapters did not augment reactive species deposition in liquids or tumor cell killing. However, MoNoS operated at kINPen standard argon fluxes significantly improved cancer organoid growth reduction and increased tumor immunogenicity, as seen by elevated calreticulin and heat-shock protein expression, along with a significantly spurred cytokine secretion profile. Moreover, the safe application of MoNoS gas plasma jet adapters was confirmed by their similar-to-superior safety profiles assessed in the hen’s egg chorioallantoic membrane (HET-CAM) coagulation and scar formation irritation assay

Vielfalt und Integration - diversitá ed integrazione - diversité et intégration: Sprache(n) in sozialen und digitalen Räumen: Eine Festschrift für Elisabeth Burr

Diese Festschrift für Elisabeth Burr stellt Vielfalt und Integration in der Sprachwissenschaft und in den Digital Humanities in den Mittelpunkt. Die Beiträge berühren zentrale Fragen im Schaffen Burrs: Wie kann Sprache und ihre Variation in Abhängigkeit von sozialen und geographischen Faktoren adäquat beschrieben werden? Wie lassen sich informatische und digitale Zugänge dafür nutzen? Verknüpft werden sie mit ihr wichtigen und aktuellen Themen aus Sozio-, Gender- und Korpuslinguistik, Dialektologie und Sprachgeographie sowie den digitalen Geisteswissenschaften. Die Beitragenden sind u. a. Stefania Spina, Thomas Krefeld, Annette Gerstenberg, Lazslo Hinyadi, Carol Chiodo und Lauren Tilton, Manuel Burghardt, Øyvind Eide, Jürgen Hermes, Andreas Witt. Ray Siemens, Arianna Ciula, Alejandro Bía sowie Rob Evans

Research priorities in land use and land-cover change for the Earth system and integrated assessment modelling

Copyright © 2010 Royal Meteorological Society and Crown Copyright.This special issue has highlighted recent and innovative methods and results that integrate observations and modelling analyses of regional to global aspect of biophysical and biogeochemical interactions of land-cover change with the climate system. Both the Earth System and the Integrated Assessment modeling communities recognize the importance of an accurate representation of land use and land-cover change to understand and quantify the interactions and feedbacks with the climate and socio-economic systems, respectively. To date, cooperation between these communities has been limited. Based on common interests, this work discusses research priorities in representing land use and land-cover change for improved collaboration across modelling, observing and measurement communities. Major research topics in land use and land-cover change are those that help us better understand (1) the interaction of land use and land cover with the climate system (e.g. carbon cycle feedbacks), (2) the provision of goods and ecosystem services by terrestrial (natural and anthropogenic) land-cover types (e.g. food production), (3) land use and management decisions and (4) opportunities and limitations for managing climate change (for both mitigation and adaptation strategies)

Chronophin regulates active vitamin B6 levels and transcriptomic features of glioblastoma cell lines cultured under non-adherent, serum-free conditions

Background: The phosphatase chronophin (CIN/PDXP) has been shown to be an important regulator of glioma cell migration and invasion. It has two known substrates: p-Ser3-cofilin, the phosphorylated form of the actin binding protein cofilin, and pyridoxal 5′-phosphate, the active form of vitamin B6. Phosphoregulation of cofilin, among other functions, plays an important role in cell migration, whereas active vitamin B6 is a cofactor for more than one hundred enzymatic reactions. The role of CIN has yet only been examined in glioblastoma cell line models derived under serum culture conditions. Results: We found that CIN is highly expressed in cells cultured under non-adherent, serum-free conditions that are thought to better mimic the in vivo situation. Furthermore, the substrates of CIN, p-Ser3-cofilin and active vitamin B6, were significantly reduced as compared to cell lines cultured in serum-containing medium. To further examine its molecular role we stably knocked down the CIN protein with two different shRNA hairpins in the glioblastoma cell lines NCH421k and NCH644. Both cell lines did not show any significant alterations in proliferation but expression of differentiation markers (such as GFAP or TUBB3) was increased in the knockdown cell lines. In addition, colony formation was significantly impaired in NCH644. Of note, in both cell lines CIN knockdown increased active vitamin B6 levels with vitamin B6 being known to be important for S-adenosylmethionine biosynthesis. Nevertheless, global histone and DNA methylation remained unaltered as was chemoresistance towards temozolomide. To further elucidate the role of phosphocofilin in glioblastoma cells we applied inhibitors for ROCK1/2 and LIMK1/2 to our model. LIMK- and ROCK-inhibitor treatment alone was not toxic for glioblastoma cells. However, it had profound, but antagonistic effects in NCH421k and NCH644 under chemotherapy. Conclusion: In non-adherent glioblastoma cell lines cultured in serum-free medium, chronophin knockdown induces phenotypic changes, e.g. in colony formation and transcription, but these are highly dependent on the cellular background. The same is true for phenotypes observed after treatment with inhibitors for kinases regulating cofilin phosphorylation (ROCKs and LIMKs). Targeting the cofilin phosphorylation pathway might therefore not be a straightforward therapeutic option in glioblastoma