פרסומים

The disclosure concerns viscous or gelled delivery systems based on oily nano-domains dispersed in a viscosified/gelled continuous aq. phase, and suitable for prolonged and/or sustained topical delivery of various active compds. [on SciFinder(R)]

Cracks develop intricate patterns on the surfaces that they create. As faceted fracture surfaces are commonly formed by slow tensile cracks in both crystalline and amorphous materials, facet formation and structure cannot reflect microscopic order. Although fracture mechanics predict that slow crack fronts should be straight and form mirror-like surfaces, facet-forming fronts propagate simultaneously within different planes separated by steps. Here we show that these steps are topological defects of crack fronts and that crack front separation into disconnected overlapping segments provides the condition for step stability. Real-time imaging of propagating crack fronts combined with surface measurements shows that crack dynamics are governed by localized steps that drift at a constant angle to the local front propagation direction while their increased dissipation couples to long-ranged elasticity to determine front shapes. We study how three-dimensional topology couples to two-dimensional fracture dynamics to provide a fundamental picture of how patterned surfaces are generated.

Classical structural biology can only provide static snapshots of biomacromolecules. Single-molecule Förster resonance energy transfer (smFRET) paved the way for studying dynamics in macromolecular structures under biologically relevant conditions. Since its first implementation in 1996, smFRET experiments have confirmed previously hypothesized mechanisms and provided new insights into many fundamental biological processes, such as DNA maintenance and repair, transcription, translation, and membrane transport. We review 22 years of contributions of smFRET to our understanding of basic mechanisms in biochemistry, molecular biology, and structural biology. Additionally, building on current state-of-the-art implementations of smFRET, we highlight possible future directions for smFRET in applications such as biosensing, high-throughput screening, and molecular diagnostics.

If a narratological book such as Monika Fludernik's Towards a 'Natural' Narratology claims to move “beyond formal narratology into the realm of pragmatics, reception theory and constructivism” (xi), what kind of outcome can we expect? If the reader is familiar with the narratological modus operandi, she will not be expecting any kind of empirical data about actual readers. As Marie-Laure Ryan notes (474, 476), a cognitive narratologist will willingly undergo a considerable theoretical and methodological ordeal just to avoid having to deal with real readers. I find this to be a remarkable confession coming from one of the eminent pioneers of cognitive narratology. This does not need to be a problem, however. In fact, narratologists' uneasiness about dealing with the reader in the reading process can be aggravated to such a pitch as to produce really great theorizing, and this, I think, is the case with Natural Narratology. Fludernik claims to be in search of the “organic frames of reading,” but the reader position constructed in her theory is synthetic through and through. In the following, I argue that this methodological unnaturalness within Natural Narratology is not a shortcoming but a productive innovation that makes it one of the cornerstones of postclassical narratology. © 2018 Johns Hopkins University Press

Building upon previous literature and insights from natural corpus data, this paper questions the theoretical bases and applicability of Information-Structural categories, such as topic and focus, and proposes an alternative approach to this field. In the proposed framework, so-called “information-structural” phenomena are epiphenomenal effects of diverse linguistic devices, related directly to a broad array of primarily intersubjective, interactional and discourse-structuring aspects of communication and language. The paper presents cross-linguistic data that support this view and proposes the ensuing directions for the systematic study of these phenomena.

The facilitative glucose transporter (GLUT) family plays a key role in metabolic homeostasis, controlling the absorption rates and rapid response to changing carbohydrate levels. The facilitative GLUT2 transporter is uniquely expressed in metabolic epithelial cells of the intestine, pancreas, liver, and kidney. GLUT2 dysfunction is associated with several pathologies, including Fanconi-Bickel syndrome, a glycogen storage disease, characterized by growth retardation and renal dysfunction. Interestingly, GLUT2 activity is modulated by its cellular localization. Membrane translocation specifically regulates GLUT2 activity in enterocytes, pancreatic β-cells, hepatocytes, and proximal tubule cells. We have established a system to visualize and quantify GLUT2 translocation, and its dynamics, by live imaging of a mCherry-hGLUT2 fusion protein in polarized epithelial cells. This system enables testing of putative modulators of GLUT2 translocation, which are potential drugs for conditions of impaired glucose homeostasis and associated nephropathy. © Springer Science+Business Media LLC 2018.

Natural killer cells (NKs) are abundant in the human decidua, regulating trophoblast invasion and angiogenesis. Several diseases of poor placental development are associated with first pregnancies, so we thus looked to characterize differences in decidual NKs (dNKs) in first versus repeated pregnancies. We discovered a population found in repeated pregnancies, which has a unique transcriptome and epigenetic signature, and is characterized by high expression of the receptors NKG2C and LILRB1. We named these cells Pregnancy Trained decidual NK cells (PTdNKs). PTdNKs have open chromatin around the enhancers of IFNG and VEGFA. Activation of PTdNKs led to increased production and secretion of IFN-gamma and VEGFalpha, with the latter supporting vascular sprouting and tumor growth. The precursors of PTdNKs seem to be found in the endometrium. Because repeated pregnancies are associated with improved placentation, we propose that PTdNKs, which are present primarily in repeated pregnancies, might be involved in proper placentation.

In dicots, the key developmental process by which immature plastids differentiate into photosynthetically competent chloroplasts commences in the shoot apical meristem (SAM), within the shoot apex. Using laser-capture microdissection and single-cell RNA sequencing methodology, we studied the changes in the transcriptome along the chloroplast developmental pathway in the shoot apex of tomato seedlings. The analysis revealed the presence of transcripts for different chloroplast functions already in the stem cell-containing region of the SAM. Thereafter, an en masse up-regulation of genes encoding for various proteins occurs, including chloroplast ribosomal proteins and proteins involved in photosynthesis, photoprotection and detoxification of reactive oxygen species. The results highlight transcriptional events that operate during chloroplast biogenesis, leading to the rapid establishment of photosynthetic competence.

Forest trees use various strategies to cope with drought stress and these strategies involve complex molecular mechanisms. Pinus halepensis Miller (Aleppo pine) is found throughout the Mediterranean basin and is one of the most drought-tolerant pine species. In order to decipher the molecular mechanisms that P. halepensis uses to withstand drought, we performed large-scale physiological and transcriptome analyses. We selected a mature tree from a semi-arid area with suboptimal growth conditions for clonal propagation through cuttings. We then used a high-throughput experimental system to continuously monitor whole-plant transpiration rates, stomatal conductance and the vapor pressure deficit. The transcriptomes of plants were examined at six physiological stages: pre-stomatal response, partial stomatal closure, minimum transpiration, post-irrigation, partial recovery and full recovery. At each stage, data from plants exposed to the drought treatment were compared with data collected from well-irrigated control plants. A drought-stressed P. halepensis transcriptome was created using paired-end RNA-seq. In total, ∼6000 differentially expressed, non-redundant transcripts were identified between drought-treated and control trees. Cluster analysis has revealed stress-induced down-regulation of transcripts related to photosynthesis, reactive oxygen species (ROS)-scavenging through the ascorbic acid (AsA)-glutathione cycle, fatty acid and cell wall biosynthesis, stomatal activity, and the biosynthesis of flavonoids and terpenoids. Up-regulated processes included chlorophyll degradation, ROS-scavenging through AsA-independent thiol-mediated pathways, abscisic acid response and accumulation of heat shock proteins, thaumatin and exordium. Recovery from drought induced strong transcription of retrotransposons, especially the retrovirus-related transposon Tnt1-94. The drought-related transcriptome illustrates this species' dynamic response to drought and recovery and unravels novel mechanisms. © The Author 2017.

Knowledge of the physicochemical properties of ingestible silver nanoparticles (AgNPs) in the human gastrointestinal tract (GIT) is essential for assessing their bioavailability, bioactivity, and potential health risks. The gastrointestinal fate of AgNPs and silver ions from a commercial dietary supplement was therefore investigated using a simulated human GIT. In the mouth, no dissolution or aggregation of AgNPs occurred, which was attributed to the neutral pH and the formation of biomolecular corona, while the silver ions formed complexes with biomolecules (Ag-biomolecule). In the stomach, aggregation of AgNPs did not occur, but extensive dissolution was observed due to the low pH and the presence of Cl–. In the fed state (after meal), 72% AgNPs (by mass) dissolved, with 74% silver ions forming Ag-biomolecule and 26% forming AgCl. In the fasted state (before meal), 76% AgNPs dissolved, with 82% silver ions forming Ag-biomolecule and 18% forming AgCl. A biomolecular corona around AgNPs, comprised of mucin with multiple sulfhydryl groups, inhibited aggregation and dissolution of AgNPs. In the small intestine, no further dissolution or aggregation of AgNPs occurred, while the silver ions existed only as Ag-biomolecule. These results provide useful information for assessing the bioavailability of ingestible AgNPs and their subsequently potential health risks, and for the safe design and utilization of AgNPs in biomedical applications.Knowledge of the physicochemical properties of ingestible silver nanoparticles (AgNPs) in the human gastrointestinal tract (GIT) is essential for assessing their bioavailability, bioactivity, and potential health risks. The gastrointestinal fate of AgNPs and silver ions from a commercial dietary supplement was therefore investigated using a simulated human GIT. In the mouth, no dissolution or aggregation of AgNPs occurred, which was attributed to the neutral pH and the formation of biomolecular corona, while the silver ions formed complexes with biomolecules (Ag-biomolecule). In the stomach, aggregation of AgNPs did not occur, but extensive dissolution was observed due to the low pH and the presence of Cl–. In the fed state (after meal), 72% AgNPs (by mass) dissolved, with 74% silver ions forming Ag-biomolecule and 26% forming AgCl. In the fasted state (before meal), 76% AgNPs dissolved, with 82% silver ions forming Ag-biomolecule and 18% forming AgCl. A biomolecular corona around AgNPs, comprised of mucin with multiple sulfhydryl groups, inhibited aggregation and dissolution of AgNPs. In the small intestine, no further dissolution or aggregation of AgNPs occurred, while the silver ions existed only as Ag-biomolecule. These results provide useful information for assessing the bioavailability of ingestible AgNPs and their subsequently potential health risks, and for the safe design and utilization of AgNPs in biomedical applications.