Lipid phase separation in vesicles enhances TRAIL-mediated cytotoxicity

Ligand spatial presentation and density play important roles in many signaling pathways mediated by cell receptors and are critical parameters when designing protein-conjugated therapeutic nanoparticles. Currently, Janus particles are most often used to spatially control ligand conjugation, but the technological challenge of manufacturing Janus particles limits adoption for translational applications. Here, we demonstrate that lipid phase separation can be used to spatially control protein presentation onto lipid vesicles. We used this system to study the density dependence of TNF-related apoptosis inducing ligand (TRAIL), a model therapeutic protein that exhibits greater cytotoxicity to cancer cells when conjugated onto a vesicle surface than when administered as a soluble protein. Using assays for apoptosis and caspase activity, we show that phase separated TRAIL vesicles induced higher cytotoxicity to Jurkat cancer cells than uniformly-conjugated TRAIL vesicles, and enhanced cytotoxicity was dependent on the TRAIL domain density. We then assessed this relationship in other cancer cell lines and demonstrated that phase separated TRAIL vesicles only enhanced cytotoxicity through one TRAIL receptor, DR5, while another TRAIL receptor, DR4, was unaffected by the TRAIL density. These results indicate unique signaling requirements for each TRAIL receptor and how TRAIL therapy could be tailored depending on the relative levels of expression for cancer receptors of interest. Overall, this work demonstrates a readily adoptable method to control protein conjugation and density on bilayer vesicles that can be easily adopted to other therapeutic nanoparticle systems to improve receptor signaling of nanoparticles targeted to cancer and diseased cells.

Control Cell Migration by Engineering Integrin Ligand Assembly

Advances in mechanistic understanding of integrin-mediated adhesion highlight the importance of precise control of ligand presentation in directing cell migration. Top-down nanopatterning limited the spatial presentation to sub-micron. To enhance it to molecular level, we propose a bottom-up nanofabrication strategy. Via self-assembly and co-assembly, precise control of ligand presentation is succeeded by varying the proportions of assembling ligand and nonfunctional peptide. Assembled nanofilaments fulfill multi-functions exerting enhancement to suppression effect on cell migration with tunable amplitudes. Self-assembled nanofilaments possessing super high ligand density selectively suppress cancer cell migration by preventing integrin/actin disassembly at cell rear, which provides new insights to ligand-density-dependent-modulation, revealing valuable inputs to therapeutic innovations in tumor metastasis.One-Sentence SummaryEngineering integrin ligand assembly from bottom-up offers a generalized tool to selectively control cell migration with tunable amplitudes.

Gender Blindness on Turkish Children’s Televisions

The representation of the dominant gender-based discourse on television inevitably affects children’s perceptions of masculinity and femininity. Gender blindness, the embodiment of gender hierarchy in which gender differences are exaggerated and attributed to natural differences between men and women, is inevitably used in the media, especially in children’s broadcasting. This study aims to reveal the gender blindness in children’s television on Turkey’s only thematic children’s television stations Minika GO and Minika Cocuk’, focusing on all local productions aired in 2020. Stuart Hall’s conceptualization of representation debates and text analysis expressed as constructing the meaning world of relationships and collective culture, guided the study. The representations are conveyed to the audience through the narration of the story in the animations, the plots of the story, the presentation of male and female characters, the use of space and images. In the cartoons, the frequency of female and male characters appearing on the screen, the physical appearance of the characters, their behavioral characteristics, and the spatial presentation in the stories were searched. As a result, it is possible to say that male and female characters are depicted unequally in all the themes studied in animations resulting in gender blindness.

CAN SPATIAL ABILITY BE TRAINED – THE ANALYSIS OF PREPARATORY COURSE FOR ENROLMENT AT THE FACULTY OF ARCHITECTURE

Spatial abilities are becoming an increasingly important predictor of success, especially in professions that balance analytical and creative thinking, such as architecture, especially with the increasing presence of digital media and technology, and the importance of the spatial presentation of one’s ideas. There are differing opinions as to whether these abilities can be improved, or whether a spatial thinking strategy can be developed. At the Faculty of Architecture and Geodesy in Banja Luka (FACEG), spatial abilities have long been part of the entrance exam, and this paper will address the analysis of preparatory teaching at FACEG in this area and the success of the entrance exam for two groups of candidates - those who attended preparatory classes and those who prepared independently.

Integrated Geodetic and Hydrographic Measurements of the Yacht Port for Nautical Charts and Dynamic Spatial Presentation

The use of geodetic and hydrographic systems, methods and measuring devices to obtain geospatial data enables integrated modeling of 3D space and related objects. Factors such as the seafloor relief of the marina and land infrastructure need to be considered to ensure safe stay of vessels in the marina. The article presents the results of bathymetric and geodetic measurements of the yacht port of the National Sailing Centre in Gdańsk. They were made with the use of several measuring methods such as a hydrographic unmanned surface vessel, GNSS positioning, enabling geodetic inventory of hydrotechnical structures and port infrastructure, as well as laser scanning that resulted in three-dimensional presentation of land objects. As a result of research and analysis, a two-dimensional bathymetric chart of the yacht port was made. Thanks to the integration of geodetic and hydrographic data, three-dimensional visualization of the marina area was obtained. The charts can be used to ensure ship navigation safety when maneuvering in port and mooring at quays.

Recapitulating complex biological signaling environments using a multiplexed, DNA-patterning approach

Elucidating how the spatial organization of extrinsic signals modulates cell behavior and drives biological processes remains largely unexplored because of challenges in controlling spatial patterning of multiple microenvironmental cues in vitro. Here, we describe a high-throughput method that directs simultaneous assembly of multiple cell types and solid-phase ligands across length scales within minutes. Our method involves lithographically defining hierarchical patterns of unique DNA oligonucleotides to which complementary strands, attached to cells and ligands-of-interest, hybridize. Highlighting our method’s power, we investigated how the spatial presentation of self-renewal ligand fibroblast growth factor-2 (FGF-2) and differentiation signal ephrin-B2 instruct single adult neural stem cell (NSC) fate. We found that NSCs have a strong spatial bias toward FGF-2 and identified an unexpected subpopulation exhibiting high neuronal differentiation despite spatially occupying patterned FGF-2 regions. Overall, our broadly applicable, DNA-directed approach enables mechanistic insight into how tissues encode regulatory information through the spatial presentation of heterogeneous signals.

Using GIS tool for presenting spatial distribution of drought

By using GIS tools, it is possible to improve the preview of hydrological processes such as evapotranspiration, precipitation, flood and drought. In order to quantify drought, different type of drought indicators have been developed such as Standardized Precipitation Index (SPI), Reconnaissance Drought Index (RDI), Standardized Precipitation Evapotranspiration Index (SPEI) or Water Surplus Variability Index (WSVI). In this paper the precipitation-based SPI indicator was applied to the monthly precipitation data from Serbia during the period 1948-2012. The data were processed in the QuantumGIS software package. For the purpose of application in the monitoring of drought at the national level, a spatial presentation of meteorological drought was obtained.

The sugar code: letters and vocabulary, writers, editors and readers and biosignificance of functional glycan–lectin pairing

Ubiquitous occurrence in Nature, abundant presence at strategically important places such as the cell surface and dynamic shifts in their profile by diverse molecular switches qualifies the glycans to serve as versatile biochemical signals. However, their exceptional structural complexity often prevents one noting how simple the rules of objective-driven assembly of glycan-encoded messages are. This review is intended to provide a tutorial for a broad readership. The principles of why carbohydrates meet all demands to be the coding section of an information transfer system, and this at unsurpassed high density, are explained. Despite appearing to be a random assortment of sugars and their substitutions, seemingly subtle structural variations in glycan chains by a sophisticated enzymatic machinery have emerged to account for their specific biological meaning. Acting as ‘readers’ of glycan-encoded information, carbohydrate-specific receptors (lectins) are a means to turn the glycans’ potential to serve as signals into a multitude of (patho)physiologically relevant responses. Once the far-reaching significance of this type of functional pairing has become clear, the various modes of spatial presentation of glycans and of carbohydrate recognition domains in lectins can be explored and rationalized. These discoveries are continuously revealing the intricacies of mutually adaptable routes to achieve essential selectivity and specificity. Equipped with these insights, readers will gain a fundamental understanding why carbohydrates form the third alphabet of life, joining the ranks of nucleotides and amino acids, and will also become aware of the importance of cellular communication via glycan–lectin recognition.