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Recent experiments show that transcription factors (TFs) indeed use the facilitated diffusion mechanism to locate their target sequences on DNA in living bacteria cells: TFs alternate between sliding motion along DNA and relocation events through the cytoplasm. From simulations and theoretical analysis we study the TF-sliding motion for a large section of the DNA-sequence of a common E. coli strain, based on the two-state TF-model with a fast-sliding search state and a recognition state enabling target detection. For the probability to detect the target before dissociating from DNA the TF-search times self-consistently depend heavily on whether or not an auxiliary operator (an accessible sequence similar to the main operator) is present in the genome section. Importantly, within our model the extent to which the interconversion rates between search and recognition states depend on the underlying nucleotide sequence is varied. A moderate dependence maximises the capability to distinguish between the main operator and similar sequences. Moreover, these auxiliary operators serve as starting points for DNA looping with the main operator, yielding a spectrum of target detection times spanning several orders of magnitude. Auxiliary operators are shown to act as funnels facilitating target detection by TFs.
The coordination of cell polarity within the plane of the tissue layer (planar polarity) is crucial for the development of diverse multicellular organisms. Small Rac/Rho-family GTPases and the actin cytoskeleton contribute to planar polarity formation at sites of polarity establishment in animals and plants. Yet, upstream pathways coordinating planar polarity differ strikingly between kingdoms. In the root of Arabidopsis thaliana, a concentration gradient of the phytohormone auxin coordinates polar recruitment of Rho-of-plant (ROP) to sites of polar epidermal hair initiation. However, little is known about cytoskeletal components and interactions that contribute to this planar polarity or about their relation to the patterning machinery. Here, we show that ACTIN7 (ACT7) represents a main actin isoform required for planar polarity of root hair positioning, interacting with the negative modulator ACTIN-INTERACTING PROTEIN1-2 (AIP1-2). ACT7, AIP1-2 and their genetic interaction are required for coordinated planar polarity of ROP downstream of ethylene signalling. Strikingly, AIP1-2 displays hair cell file-enriched expression, restricted by WEREWOLF (WER)-dependent patterning and modified by ethylene and auxin action. Hence, our findings reveal AIP1-2, expressed under control of the WER-dependent patterning machinery and the ethylene signalling pathway, as a modulator of actin-mediated planar polarity.
Patterned differentiation of distinct cell types is essential for the development of multicellular organisms. The root epidermis of Arabidopsis thaliana is composed of alternating files of root hair and non-hair cells and represents a model system for studying the control of cell-fate acquisition. Epidermal cell fate is regulated by a network of genes that translate positional information from the underlying cortical cell layer into a specific pattern of differentiated cells. While much is known about the genes of this network, new players continue to be discovered. Here we show that the SABRE (SAB) gene, known to mediate microtubule organization, anisotropic cell growth and planar polarity, has an effect on root epidermal hair cell patterning. Loss of SAB function results in ectopic root hair formation and destabilizes the expression of cell fate and differentiation markers in the root epidermis, including expression of the WEREWOLF (WER) and GLABRA2 (GL2) genes. Double mutant analysis reveal that wer and caprice (cpc) mutants, defective in core components of the epidermal patterning pathway, genetically interact with sab. This suggests that SAB may act on epidermal patterning upstream of WER and CPC. Hence, we provide evidence for a role of SAB in root epidermal patterning by affecting cell-fate stabilization. Our work opens the door for future studies addressing SAB-dependent functions of the cytoskeleton during root epidermal patterning.
Der Nötigungsnotstand
(2015)
Foreign Accent Syndrome
(2015)
Fluid force microscopy combines the positional accuracy and force sensitivity of an atomic
force microscope (AFM) with nanofluidics via a microchanneled cantilever. However, adequate
loading and cleaning procedures for such AFM micropipettes are required for various
application situations. Here, a new frontloading procedure is described for an AFM micropipette
functioning as a force- and pressure-controlled microscale liquid dispenser. This frontloading
procedure seems especially attractive when using target substances featuring high
costs or low available amounts. Here, the AFM micropipette could be filled from the tip side
with liquid from a previously applied droplet with a volume of only a few μL using a short
low-pressure pulse. The liquid-loaded AFM micropipettes could be then applied for experiments
in air or liquid environments. AFM micropipette frontloading was evaluated with the
well-known organic fluorescent dye rhodamine 6G and the AlexaFluor647-labeled antibody
goat anti-rat IgG as an example of a larger biological compound. After micropipette usage,
specific cleaning procedures were tested. Furthermore, a storage method is described, at
which the AFM micropipettes could be stored for a few hours up to several days without drying
out or clogging of the microchannel. In summary, the rapid, versatile and cost-efficient
frontloading and cleaning procedure for the repeated usage of a single AFM micropipette is
beneficial for various application situations from specific surface modifications through to
local manipulation of living cells, and provides a simplified and faster handling for already
known experiments with fluid force microscopy.
Schreiben aus der Asche
(2015)
Im Beitrag wird die Beziehung zwischen Leben, Schreiben und Denken des Autors Wolfgang Hilbig am Rande des Mülls im Hilbigschen Werk nachgezeichnet. Es kommt auch darauf an, Hilbigs oppositionelle Haltung im Kontext der Ideologie der DDR-Gesellschaft zu verdeutlichen. Als herausgehobener Metapher seines Denkens und Schreibens wird dabei der „Asche“ nachgegangen.
Die Gegenwart der Zukunft
(2015)
Die Studieneingangsphase stellt für Studierende eine Schlüsselphase des tertiären Ausbildungsabschnitts dar. Fachwissenschaftliches Wissen wird praxisfern vermittelt und die Studierenden können die Zusammenhänge zwischen den Themenfeldern der verschiedenen Vorlesungen nicht erkennen. Zur Verbesserung der Situation wurde ein Workshop entwickelt, der die Verbindung der Programmierung und der Datenstrukturen vertieft. Dabei wird das Spiel Go-Moku1 als Android-App von den Studierenden selbständig entwickelt. Die Kombination aus Software (Java, Android-SDK) und Hardware (Tablet-Computer) für ein kleines realistisches Softwareprojekt stellt für die Studierenden eine neue Erfahrung dar.
The simulation of the optical properties of supramolecular aggregates requires the development of methods, which are able to treat a large number of coupled chromophores interacting with the environment. Since it is currently not possible to treat large systems by quantum chemistry, the Frenkel exciton model is a valuable alternative. In this work we show how the Frenkel exciton model can be extended in order to explain the excitonic spectra of a specific double-walled tubular dye aggregate explicitly taking into account dispersive energy shifts of ground and excited states due to van der Waals interaction with all surrounding molecules. The experimentally observed splitting is well explained by the site-dependent energy shift of molecules placed at the inner or outer side of the double-walled tube, respectively. Therefore we can conclude that inclusion of the site-dependent dispersive effect in the theoretical description of optical properties of nanoscaled dye aggregates is mandatory.
Kreise - Punkte - Linien
(2015)
Motivated by conflicting evidence in the literature, we re-assessed the role of facial feedback when detecting quantitative or qualitative changes in others’ emotional expressions. Fifty-three healthy adults observed self-paced morph sequences where the emotional facial expression either changed quantitatively (i.e., sad-to-neutral, neutral-to-sad, happy-to-neutral, neutral-to-happy) or qualitatively (i.e. from sad to happy, or from happy to sad). Observers held a pen in their own mouth to induce smiling or frowning during the detection task. When morph sequences started or ended with neutral expressions we replicated a congruency effect: Happiness was perceived longer and sooner while smiling; sadness was perceived longer and sooner while frowning. Interestingly, no such congruency effects occurred for transitions between emotional expressions. These results suggest that facial feedback is especially useful when evaluating the intensity of a facial expression, but less so when we have to recognize which emotion our counterpart is expressing.
The paper aims at considering characteristics from one field of contemporary visual studies that has for a long time been neglected in academic research: Pictorial signs on Social Network Sites (SNS) are an outstanding class of semiotic resources that is greatly shaped by processes of technological and collective sign production and distribution. A brief examination of the scholarly research on the pragmatics and semiotics of pictorial signs on SNS shows that the heterogeneity of visual signs is often neglected and that it mostly concentrates on one aspect of these pictorial signs: their technological production or their purpose for individual self-disclosure. The paper therefore considers the semiosis of pictorial signs on SNS in a holistic perspective as one the one hand produced by individual and collective meaning making as well as on the other hand a product of technological framing. It therefore develops a techno-semiotic pragmatic account that takes into consideration both processes. Starting from a prominent class of pictorial signs on SNS during Tunisian Revolution, the Tunisian Flag graphics, the paper than shows that communicative and social interaction functions on the graphic interface of SNS (‘like’-function, sharing and commenting option) are not only directly inscribed into the pictorial frame, but also greatly influence the reading of a pictorial sign. The location of images on the SNS’ interface has an impact on its meaning and on the social functions of a pictorial sign, as profile pictures are directly linked to the online identity of the user. Through technological sign processing, the polysemy of the image is reduced. We therefore consider the images on the one hand as individual self-narratives and on the other as instances of SNS’ visual culture that brings out dominant visual codes but also allows social and political movements to spread.
Antiplasmodial and cytotoxic activities of the constituents of Turraea robusta and Turraea nilotica
(2015)
Ethnopharmacological relevance: Turraea robusta and Turraea nilotica are African medicinal plants used for the treatment of a wide variety of diseases, including malaria. The genus Turraea is rich in limonoids and other triterpenoids known to possess various biological activities.
Materials and methods: From the stem bark of T. robusta six compounds, and from various parts of T nilotica eleven compounds were isolated by the use of a combination of chromatographic techniques. The structures of the isolated compounds were elucidated using NMR and MS, whilst the relative configuration of one of the isolated compounds, toonapubesin F, was established by X-ray crystallography. The antiplasmodial activities of the crude extracts and the isolated constituents against the D6 and W2 strains of Plasmodium falciparum were determined using the semiautomated micro dilution technique that measures the ability of the extracts to inhibit the incorporation of (G-H-3, where G is guanine) hypoxanthine into the malaria parasite. The cytotoxicity of the crude extracts and their isolated constituents was evaluated against the mammalian cell lines African monkey kidney (vero), mouse breast cancer (4T1) and human larynx carcinoma (HEp2).
Results: The extracts showed good to moderate antiplasmodial activities, where the extract of the stem bark of T. robusta was also cytotoxic against the 4T1 and the HEp2 cells (IC50 < 10 mu g/ml). The compounds isolated from these extracts were characterized as limonoids, protolimonoids and phytosterol glucosides. These compounds showed good to moderate activities with the most active one being azadironolide, IC50 2.4 +/- 0.03 mu M and 1.1 +/- 0.01 mu M against the D6 and W2 strains of Plasmodium falciparum, respectively; all other compounds possessed IC50 14.4-40.5 mu M. None of the compounds showed significant cytotoxicity against vero cells, yet four of them were toxic against the 4T1 and HEp2 cancer cell lines with piscidinol A having IC50 8.0 +/- 0.03 and 8.4 +/- 0.01 mu M against the 4T1 and HEp2 cells, respectively. Diacetylation of piscidinol A resulted in reduced cytotoxicity.
Conclusion: From the medicinal plants T. robusta and T. nilotica, twelve compounds were isolated and characterized; two of the isolated compounds, namely 11-epi-toonacilin and azadironolide showed good antiplasmodial activity with the highest selectivity indices. (C) 2015 The Authors. Published by Elsevier Ireland Ltd.
Texture mapping is a key technology in computer graphics. For the visual design of 3D scenes, in particular, effective texturing depends significantly on how important contents are expressed, e.g., by preserving global salient structures, and how their depiction is cognitively processed by the user in an application context. Edge-preserving image filtering is one key approach to address these concerns. Much research has focused on applying image filters in a post-process stage to generate artistically stylized depictions. However, these approaches generally do not preserve depth cues, which are important for the perception of 3D visualization (e.g., texture gradient). To this end, filtering is required that processes texture data coherently with respect to linear perspective and spatial relationships. In this work, we present an approach for texturing 3D scenes with perspective coherence by arbitrary image filters. We propose decoupled deferred texturing with (1) caching strategies to interactively perform image filtering prior to texture mapping and (2) for each mipmap level separately to enable a progressive level of abstraction, using (3) direct interaction interfaces to parameterize the visualization according to spatial, semantic, and thematic data. We demonstrate the potentials of our method by several applications using touch or natural language inputs to serve the different interests of users in specific information, including illustrative visualization, focus+context visualization, geometric detail removal, and semantic depth of field. The approach supports frame-to-frame coherence, order-independent transparency, multitexturing, and content-based filtering. In addition, it seamlessly integrates into real-time rendering pipelines and is extensible for custom interaction techniques. (C) 2015 Elsevier Ltd. All rights reserved.
Cartography-Oriented Design of 3D Geospatial Information Visualization - Overview and Techniques
(2015)
In economy, society and personal life map-based interactive geospatial visualization becomes a natural element of a growing number of applications and systems. The visualization of 3D geospatial information, however, raises the question how to represent the information in an effective way. Considerable research has been done in technology-driven directions in the fields of cartography and computer graphics (e.g., design principles, visualization techniques). Here, non-photorealistic rendering (NPR) represents a promising visualization category - situated between both fields - that offers a large number of degrees for the cartography-oriented visual design of complex 2D and 3D geospatial information for a given application context. Still today, however, specifications and techniques for mapping cartographic design principles to the state-of-the-art rendering pipeline of 3D computer graphics remain to be explored. This paper revisits cartographic design principles for 3D geospatial visualization and introduces an extended 3D semiotic model that complies with the general, interactive visualization pipeline. Based on this model, we propose NPR techniques to interactively synthesize cartographic renditions of basic feature types, such as terrain, water, and buildings. In particular, it includes a novel iconification concept to seamlessly interpolate between photorealistic and cartographic representations of 3D landmarks. Our work concludes with a discussion of open challenges in this field of research, including topics, such as user interaction and evaluation.
Background: African weakly-electric fishes of the family Mormyridae are able to produce and perceive weak electric signals (typically less than one volt in amplitude) owing to the presence of a specialized, muscle-derived electric organ (EO) in their tail region. Such electric signals, also known as Electric Organ Discharges (EODs), are used for objects/prey localization, for the identification of conspecifics, and in social and reproductive behaviour. This feature might have promoted the adaptive radiation of this family by acting as an effective pre-zygotic isolation mechanism. Despite the physiological and evolutionary importance of this trait, the investigation of the genetic basis of its function and modification has so far remained limited. In this study, we aim at: i) identifying constitutive differences in terms of gene expression between electric organ and skeletal muscle (SM) in two mormyrid species of the genus Campylomormyrus: C. compressirostris and C. tshokwe, and ii) exploring cross-specific patterns of gene expression within the two tissues among C. compressirostris, C. tshokwe, and the outgroup species Gnathonemus petersii.
Results: Twelve paired-end (100 bp) strand-specific RNA-seq Illumina libraries were sequenced, producing circa 330 M quality-filtered short read pairs. The obtained reads were assembled de novo into four reference transcriptomes. In silico cross-tissue DE-analysis allowed us to identify 271 shared differentially expressed genes between EO and SM in C. compressirostris and C. tshokwe. Many of these genes correspond to myogenic factors, ion channels and pumps, and genes involved in several metabolic pathways. Cross-species analysis has revealed that the electric organ transcriptome is more variable in terms of gene expression levels across species than the skeletal muscle transcriptome.
Conclusions: The data obtained indicate that: i) the loss of contractile activity and the decoupling of the excitation-contraction processes are reflected by the down-regulation of the corresponding genes in the electric organ's transcriptome; ii) the metabolic activity of the EO might be specialized towards the production and turn-over of membrane structures; iii) several ion channels are highly expressed in the EO in order to increase excitability; iv) several myogenic factors might be down-regulated by transcription repressors in the EO.
The electric organ (EO) of weakly electric mormyrids consists of flat, disk-shaped electrocytes with distinct anterior and posterior faces. There are multiple species-characteristic patterns in the geometry of the electrocytes and their innervation. To further correlate electric organ discharge (EOD) with EO anatomy, we examined four species of the mormyrid genus Campylomormyrus possessing clearly distinct EODs. In C. compressirostris, C. numenius, and C. tshokwe, all of which display biphasic EODs, the posterior face of the electrocytes forms evaginations merging to a stalk system receiving the innervation. In C. tamandua that emits a triphasic EOD, the small stalks of the electrocyte penetrate the electrocyte anteriorly before merging on the anterior side to receive the innervation. Additional differences in electrocyte anatomy among the former three species with the same EO geometry could be associated with further characteristics of their EODs. Furthermore, in C. numenius, ontogenetic changes in EO anatomy correlate with profound changes in the EOD. In the juvenile the anterior face of the electrocyte is smooth, whereas in the adult it exhibits pronounced surface foldings. This anatomical difference, together with disparities in the degree of stalk furcation, probably contributes to the about 12 times longer EOD in the adult.
Audition in bats serves passive orientation, alerting functions and communication as it does in other vertebrates. In addition, bats have evolved echolocation for orientation and prey detection and capture. This put a selective pressure on the auditory system in regard to echolocation-relevant temporal computation and frequency analysis. The present review attempts to evaluate in which respect the processing modules of bat auditory cortex (AC) are a model for typical mammalian AC function or are designed for echolocation-unique purposes. We conclude that, while cortical area arrangement and cortical frequency processing does not deviate greatly from that of other mammals, the echo delay time-sensitive dorsal cortex regions contain special designs for very powerful time perception. Different bat species have either a unique chronotopic cortex topography or a distributed salt-and-pepper representation of echo delay. The two designs seem to enable similar behavioural performance.
In this essay, I explore various politics of mimicry on Ludwig Leichhardt's second Australian expedition. Following Michael Taussig, I read mimicry as embedded in a complex economy of gift exchange which disrupts the binary categories of self and other, subject and object, man and nature. Mimetic exchanges, in other words, bear the potential for a non-dualistic dynamics of depropriation, a dynamics which may be avowed or disavowed by various actors in the colonial encounter. Focussing on three actors in particularLudwig Leichhardt himself, his British botanist Daniel Bunce, and the intriguing figure of Mr Turner, an Indigenous AustralianI trace the ways in which mimicry-as-depropriation is dealt with across the colonial archive.
Despite the wide range of industrial applications for ceria-zirconia mixed oxides (CexZr1-xO2), the complex correlation between their atomic structure and catalytic performance is still under debate. Catalytically interesting CexZr1-xO2 nanomaterials can form homogeneous solid solutions and, depending on the composition, show phase separation under the formation of small domains. The characterization of homogeneity and atomic structure of these materials remains a major challenge. High-resolution emission spectroscopy recorded under cryogenic conditions using Eu3+ as a structural probe in doped CeZrO2 nanoparticles offers an effective way to identify the different atomic environments of the Eu3+ dopants and, subsequently, to monitor structural parameters of the ceria-zirconia mixed oxides. It is found that, in stoichiometric CeZrO2:Eu3+, phase separation occurs at elevated temperatures beginning with the gradual formation of (pseudo)cubic crystallites in the amorphous materials at 500 degrees C and a sudden phase separation into tetragonal, zirconia-rich and cubic, ceria-rich domains over 900 degrees C. The presented technique allows us to easily monitor subtle changes even in amorphous, high surface area samples, yielding structural information not accessible by conventional techniques such as X-ray diffraction (XRD) and Raman. Moreover, in reference experiments investigating the reducibility of largely unordered Ce0.2Zr0.8O2:Eu3+, the main reduction peak in temperature-programmed reduction measurements appeared at exceptionally low temperatures below 200 degrees C, thus suggesting the outstanding potential of this oxide to activate catalytic oxidation reactions. This effect was found to be dependent on the amount of Eu3+ dopant introduced into the CeZrO2 matrix as well as to be connected to the atomic structure of the catalyst material.
Biallelic mutations in the gene encoding centrosomal CDK5RAP2 lead to autosomal recessive primary microcephaly (MCPH), a disorder characterized by pronounced reduction in volume of otherwise architectonical normal brains and intellectual deficit. The current model for the microcephaly phenotype in MCPH invokes a premature shift from symmetric to asymmetric neural progenitor-cell divisions with a subsequent depletion of the progenitor pool. The isolated neural phenotype, despite the ubiquitous expression of CDK5RAP2, and reports of progressive microcephaly in individual MCPH cases prompted us to investigate neural and non-neural differentiation of Cdk5rap2-depleted and control murine embryonic stem cells (mESC). We demonstrate an accumulating proliferation defect of neurally differentiating Cdk5rap2-depleted mESC and cell death of proliferative and early postmitotic cells. A similar effect does not occur in non-neural differentiation into beating cardiomyocytes, which is in line with the lack of non-central nervous system features in MCPH patients. Our data suggest that MCPH is not only caused by premature differentiation of progenitors, but also by reduced propagation and survival of neural progenitors.
The current eukaryotic tree of life groups most eukaryotes into one of five supergroups, the Opisthokonta, Amoebozoa, Archaeplastida, Excavata and SAR (Stramenopile, Alveolata, Rhizaria). Molecular and comparative morphological analyses revealed that the last eukaryotic common ancestor (LECA) already contained a rather sophisticated equipment of organelles including a mitochondrion, an endomembrane system, a nucleus with a lamina, a microtubule-organizing center (MTOC), and a flagellar apparatus. Recent studies of MTOCs, basal bodies/centrioles, and nuclear envelope organization of organisms in different supergroups have clarified our picture of how the nucleus and MTOCs co-evolved from LECA to extant eukaryotes. In this review we summarize these findings with special emphasis on valuable contributions of research on a lamin-like protein, nuclear envelope proteins, and the MTOC in the amoebozoan model organism Dictyostelium discoideum. (C) 2015 Elsevier GmbH. All rights reserved.
We discuss an intervention programme for kindergarten and school teachers' continuing education in Germany that targets biases against language outside a perceived monolingual ‘standard’ and its speakers. The programme combines anti-bias methods relating to linguistic diversity with objectives of raising critical language awareness. Evaluation through teachers' workshops in Berlin and Brandenburg points to positive and enduring attitudinal changes in participants, but not in control groups that did not attend workshops, and effects were independent of personal variables gender and teaching subject and only weakly associated with age. We relate these effects to such programme features as indirect and inclusive methods that foster active engagement, and the combination of ‘safer’ topics targeting attitudes towards linguistic structures with more challenging ones dealing with the discrimination of speakers.
Processes having the same bridges as a given reference Markov process constitute its reciprocal class. In this paper we study the reciprocal class of compound Poisson processes whose jumps belong to a finite set . We propose a characterization of the reciprocal class as the unique set of probability measures on which a family of time and space transformations induces the same density, expressed in terms of the reciprocal invariants. The geometry of plays a crucial role in the design of the transformations, and we use tools from discrete geometry to obtain an optimal characterization. We deduce explicit conditions for two Markov jump processes to belong to the same class. Finally, we provide a natural interpretation of the invariants as short-time asymptotics for the probability that the reference process makes a cycle around its current state.
This article expands our current knowledge about ministerial selection in coalition governments and analyses why ministerial candidates succeed in acquiring a cabinet position after general elections. It argues that political parties bargain over potential office-holders during government-formation processes, selecting future cabinet ministers from an emerging bargaining pool'. The article draws upon a new dataset comprising all ministrable candidates discussed by political parties during eight government-formation processes in Germany between 1983 and 2009. The conditional logit regression analysis reveals that temporal dynamics, such as the day she enters the pool, have a significant effect on her success in achieving a cabinet position. Other determinants of ministerial selection discussed in the existing literature, such as party and parliamentary expertise, are less relevant for achieving ministerial office. The article concludes that scholarship on ministerial selection requires a stronger emphasis for its endogenous nature in government-formation as well as the relevance of temporal dynamics in such processes.
The aim of this work was to verify the processing of pronominal anaphora by children that have attention deficit hyperactivity disorder or dyslexia. The sample studied consisted of 75 children that speak German, which read two texts of 80 words containing pronominal anaphora. The eye movements of all participants were recorded and, to make sure they were reading with attention, two activities that tested reading comprehension were proposed. Through the analysis of eye movements, specifically the fixations, the data indicate that children with disorders have difficulty to process the pronominal anaphora, especially dyslexic children.
The self-association properties of anti-HIV catanionic dendrimers as multivalent galactosylceramide (GalCer)-derived inhibitors are presented. The study was designed to elucidate the origin of the relatively high cytotoxicity values of these antiHIV catanionic dendrimers, which have previously been found to exhibit in vitro anti-HIV activity in the submicromolar range. The physicochemical properties of these catanionic dendrimers were studied to tentatively correlate the structural parameters with self-association and biological properties. We can conclude from this study that the absence of correlation between the hydrophobicity and the cytotoxicity of the catanionic systems could be explained by the partial segregation of the different partners of the catanionic entities.
Epigenetic silencing of tumor suppressor genes is involved in early transforming events and has a high impact on colorectal carcinogenesis. Likewise, colon cancers that derive from chronically inflamed bowel diseases frequently exhibit epigenetic changes. But there is little data about epigenetic aberrations causing colorectal cancer in chronically inflamed tissue. The aim of the present study was to evaluate the aberrant gain of methylation in the gene promoters of VIM, TFPI2 and ITGA4 as putative early markers in the development from inflamed tissue via precancerous lesions toward colorectal cancer.
Initial screening of different cancer cell lines by using methylation-specific PCR revealed a putative colon cancer-specific methylation pattern. Additionally, a demethylation assay was performed to investigate the methylation-dependent gene silencing of ITGA4. The candidate markers were analyzed in colonic tissue specimens from patients with colorectal cancer (n = 15), adenomas (n = 76), serrated lesions (n = 13), chronic inflammation (n = 10) and normal mucosal samples (n = 9).
A high methylation frequency of VIM (55.6 %) was observed in normal colon tissue, whereas ITGA4 and TFPI2 were completely unmethylated in controls. A significant gain of methylation frequency with progression of disease as well as an age-dependent effect was detectable for TFPI2. ITGA4 methylation frequency was high in precancerous and cancerous tissues as well as in inflammatory bowel diseases (IBD).
The already established methylation marker VIM does not permit a specific and sensitive discrimination of healthy and neoplastic tissue. The methylation markers ITGA4 and TFPI2 seem to be suitable risk markers for inflammation-associated colon cancer.
Information on extreme precipitation for future climate is needed to assess the changes in the frequency and intensity of flooding. The primary source of information in climate change impact studies is climate model projections. However, due to the coarse resolution and biases of these models, they cannot be directly used in hydrological models. Hence, statistical downscaling is necessary to address climate change impacts at the catchment scale.
This study compares eight statistical downscaling methods (SDMs) often used in climate change impact studies. Four methods are based on change factors (CFs), three are bias correction (BC) methods, and one is a perfect prognosis method. The eight methods are used to downscale precipitation output from 15 regional climate models (RCMs) from the ENSEMBLES project for 11 catchments in Europe. The overall results point to an increase in extreme precipitation in most catchments in both winter and summer. For individual catchments, the downscaled time series tend to agree on the direction of the change but differ in the magnitude. Differences between the SDMs vary between the catchments and depend on the season analysed. Similarly, general conclusions cannot be drawn regarding the differences between CFs and BC methods. The performance of the BC methods during the control period also depends on the catchment, but in most cases they represent an improvement compared to RCM outputs. Analysis of the variance in the ensemble of RCMs and SDMs indicates that at least 30% and up to approximately half of the total variance is derived from the SDMs. This study illustrates the large variability in the expected changes in extreme precipitation and highlights the need for considering an ensemble of both SDMs and climate models. Recommendations are provided for the selection of the most suitable SDMs to include in the analysis.
Trade plays a key role in the spread of alien species and has arguably contributed to the recent enormous acceleration of biological invasions, thus homogenizing biotas worldwide. Combining data on 60-year trends of bilateral trade, as well as on biodiversity and climate, we modeled the global spread of plant species among 147 countries. The model results were compared with a recently compiled unique global data set on numbers of naturalized alien vascular plant species representing the most comprehensive collection of naturalized plant distributions currently available. The model identifies major source regions, introduction routes, and hot spots of plant invasions that agree well with observed naturalized plant numbers. In contrast to common knowledge, we show that the 'imperialist dogma,' stating that Europe has been a net exporter of naturalized plants since colonial times, does not hold for the past 60 years, when more naturalized plants were being imported to than exported from Europe. Our results highlight that the current distribution of naturalized plants is best predicted by socioeconomic activities 20 years ago. We took advantage of the observed time lag and used trade developments until recent times to predict naturalized plant trajectories for the next two decades. This shows that particularly strong increases in naturalized plant numbers are expected in the next 20 years for emerging economies in megadiverse regions. The interaction with predicted future climate change will increase invasions in northern temperate countries and reduce them in tropical and (sub) tropical regions, yet not by enough to cancel out the trade-related increase.
Introduction
The transition from cross-fertilisation (outcrossing) to self-fertilisation (selfing) frequently coincides with changes towards a floral morphology that optimises self-pollination, the selfing syndrome. Population genetic studies have reported the existence of both outcrossing and selfing populations in Arabis alpina (Brassicaceae), which is an emerging model species for studying the molecular basis of perenniality and local adaptation. It is unknown whether its selfing populations have evolved a selfing syndrome.
Methods
Using macro-photography, microscopy and automated cell counting, we compared floral syndromes (size, herkogamy, pollen and ovule numbers) between three outcrossing populations from the Apuan Alps and three selfing populations from the Western and Central Alps (Maritime Alps and Dolomites). In addition, we genotyped the plants for 12 microsatellite loci to confirm previous measures of diversity and inbreeding coefficients based on allozymes, and performed Bayesian clustering.
Results and Discussion
Plants from the three selfing populations had markedly smaller flowers, less herkogamy and lower pollen production than plants from the three outcrossing populations, whereas pistil length and ovule number have remained constant. Compared to allozymes, microsatellite variation was higher, but revealed similar patterns of low diversity and high Fis in selfing populations. Bayesian clustering revealed two clusters. The first cluster contained the three outcrossing populations from the Apuan Alps, the second contained the three selfing populations from the Maritime Alps and Dolomites.
Conclusion
We conclude that in comparison to three outcrossing populations, three populations with high selfing rates are characterised by a flower morphology that is closer to the selfing syndrome. The presence of outcrossing and selfing floral syndromes within a single species will facilitate unravelling the genetic basis of the selfing syndrome, and addressing which selective forces drive its evolution.
We compute explicitly, and without any extra regularity assumptions, the large time limit of the fibrewise heat operator for Bismut-Lott type superconnections in the L-2-setting. This is motivated by index theory on certain non-compact spaces (families of manifolds with cocompact group action) where the convergence of the heat operator at large time implies refined L-2-index formulas.
As applications, we prove a local L-2-index theorem for families of signature operators and an L-2-Bismut-Lott theorem, expressing the Becker-Gottlieb transfer of flat bundles in terms of Kamber-Tondeur classes. With slightly stronger regularity we obtain the respective refined versions: we construct L-2-eta forms and L-2-torsion forms as transgression forms.
Botulinum toxin is a bacterial toxin that inhibits neurotransmitter release from neurons and thereby causes a flaccid paralysis. It is used as drug to treat a number of serious ailments and, more frequently, for aesthetic medical interventions. Botulinum toxin for pharmacological applications is isolated from bacterial cultures. Due to partial denaturation of the protein, the specific activity of these preparations shows large variations. Because of its extreme potential toxicity, pharmacological preparations must be carefully tested for their activity. For the current gold standard, the mouse lethality assay, several hundred thousand mice are killed per year. Alternative methods have been developed that suffer from one or more of the following deficits: In vitro enzyme assays test only the activity of the catalytic subunit of the toxin. Enzymatic and cell based immunological assays are specific for just one of the different serotypes. The current study takes a completely different approach that overcomes these limitations: Neuronal cell lines were stably transfected with plasmids coding for luciferases of different species, which were N-terminally tagged with leader sequences that redirect the luciferase into neuro-secretory vesicles. From these vesicles, luciferases were released upon depolarization of the cells. The depolarization-dependent release was efficiently inhibited by botulinum toxin in a concentration range (1 to 100 pM) that is used in pharmacological preparations. The new assay might thus be an alternative to the mouse lethality assay and the immunological assays already in use.
Xenobiotics may interfere with the hypothalamic-pituitary-thyroid endocrine axis by inducing enzymes that inactivate thyroid hormones and thereby reduce the metabolic rate. This induction results from an activation of xeno-sensing nuclear receptors. The current study shows that benzo[a]pyrene, a frequent contaminant of processed food and activator of the arylhydrocarbon receptor (AhR) activated the promoter and induced the transcription of the nuclear receptor constitutive androstane receptor (CAR, NR1I3) in rat hepatocytes. Likewise, phenobarbital induced the AhR transcription. This mutual induction of the nuclear receptors enhanced the phenobarbital-dependent induction of the prototypic CAR target gene Cyp2b1 as well as the AhR-dependent induction of UDP-glucuronosyltransferases. In both cases, the induction by the combination of both xenobiotics was more than the sum of the induction by either substance alone. By inducing the AhR, phenobarbital enhanced the benzo[a]pyrene-dependent reduction of thyroid hormone half-life and the benzo[a]pyrene-dependent increase in the rate of thyroid hormone glucuronide formation in hepatocyte cultures. CAR ligands might thus augment the endocrine disrupting potential of AhR activators by an induction of the AhR. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
Cancer cachexia, of which the most notable symptom is severe and rapid weight loss, is present in the majority of patients with advanced cancer. Inflammatory mediators play an important role in the development of cachexia, envisaged as a chronic inflammatory syndrome. The white adipose tissue (WAT) is one of the first compartments affected in cancer cachexia and suffers a high rate of lipolysis. It secretes several cytokines capable of directly regulating intermediate metabolism. A common pathway in the regulation of the expression of pro-inflammatory cytokines in WAT is the activation of the nuclear transcription factor kappa-B (NF-B). We have examined the gene expression of the subunits NF-Bp65 and NF-Bp50, as well as NF-Bp65 and NF-Bp50 binding, the gene expression of pro-inflammatory mediators under NF-B control (IL-1, IL-6, INF-, TNF-, MCP-1), and its inhibitory protein, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IB-). The observational study involved 35 patients (control group, n = 12 and cancer group, n = 23, further divided into cachectic and non-cachectic). NF-Bp65 and its target genes expression (TNF-, IL-1, MCP-1 and IB-) were significantly higher in cachectic cancer patients. Moreover, NF-Bp65 gene expression correlated positively with the expression of its target genes. The results strongly suggest that the NF-B pathway plays a role in the promotion of WAT inflammation during cachexia.