Local mechanical cues can affect crucial fate decisions of living cells. Transepithelial stress has been discussed in the context of epithelial monolayers, but the lack of appropriate experimental systems leads current studies to approximate it simply as an in-plane stress. To evaluate possible contribution of force vectors acting in other directions, double epithelium in a 3D-printed "GeminiChip" containing a sessile and a pendant channel is reconstituted. Intriguingly, the sessile epithelia is prone to apoptotic cell extrusion upon crowding, whereas the pendant counterpart favors live cell delamination. Transcriptome analyses show upregulation of RhoA, BMP2, and hypoxia-signaling genes in the pendant epithelium, consistent with the onset of an epithelial-mesenchymal transition program. HepG2 microtumor spheroids also display differential spreading patterns in the sessile and pendant configuration. Using this multilayered GeminiChip, these results uncover a progressive yet critical role of perpendicular force vectors in collective cell behaviors and point at fundamental importance of these forces in the biology of cancer.
Johnny N. Naoum, Alshanski, Israel , Gitlin-Domagalska, Agata , Bentolila, Moshe , Gilon, Chaim , ו Hurevich, Mattan . 2019. “Diffusion-Enhanced Amide Bond Formation On A Solid Support”. Organic Process Research & Development, 23, 12, Pp. 2733-2739. doi:10.1021/acs.oprd.9b00398. תקציר
Mixing of polystyrene resins in solid-phase synthesis is performed by shaking or gentle agitation of the reaction vessel to avoid breaking the brittle beads. These mixing strategies result in poor diffusion to and into the beads. Using a large excess of reagents is the common way to compensate for these deficiencies. We use fast overhead stirring for performing coupling reactions on a solid support. We show that fast overhead stirring enhances the efficiency of amide bond formation on the solid support compared to the state-of-the-art mixing method, while preserving the integrity of the beads. We find that fast overhead stirring minimizes the effect of decomposition of the activated species by increasing the diffusion-dependent coupling reaction. This allows decreasing the excess of reagents used for the multistep synthesis of peptides, thus providing a greener and more sustainable alternative for peptide synthesis on solid supports.
Online Social Networking Sites (SNSs) are immensely popular, especially among adolescents. Activity on these sites leaves digital footprints, which may be used to study online behavioral correlates of adolescent psychological distress and to, ultimately, improve detection and intervention efforts. In the present work, we explore the digital footprints of adolescent depression, social rejection, and victimization of bullying on Facebook. Two consecutive studies were conducted among Israeli adolescents (N = 86 and N = 162). We collected a range of Facebook activity features, as well as self-report measurements of depression, social rejection, and victimization of bullying. Findings from Study 1 demonstrate that explicit distress references in Facebook postings (e.g., "Life sucks, I want to die") predict depression among adolescents, but that such explicit distress references are rare. In Study 2, we applied a bottom-up research methodology along with the previous top-down, theory driven approach. Study 2 demonstrates that less explicit features of Facebook behavior predict social rejection and victimization of bullying. These features include ’posts by others’, ’check-ins’, ’gothic and dark content’, ’other people in pictures’, and ’positive attitudes towards others’. The potential, promises and limitations of using digital Facebook footprints for the detection of adolescent psychological distress are discussed.
Evgeniy Mervinejsky, Alshanski, Israel , Buchwald, Jorg , Dianat, Arezoo , Loncaric, Ivor , Lazic, Predrag , Crljen, Zeljko , Gutierrez, Rafael , Cuniberti, Gianaurelio , Hurevich, Mattan , ו Yitzchaik, Shlomo . 2019. “Direct Assembly And Metal-Ion Binding Properties Of Oxytocin Monolayer On Gold Surfaces”. Langmuir, 35, 34, Pp. 11114-11122. doi:10.1021/acs.langmuir.9b01830. תקציר
Peptides are very common recognition entities that are usually attached to surfaces using multistep processes. These processes require modification of the native peptides and of the substrates. Using functional groups in native peptides for their assembly on surfaces without affecting their biological activity can facilitate the preparation of biosensors. Herein, we present a simple single-step formation of native oxytocin monolayer on gold surface. These surfaces were characterized by atomic force spectroscopy, spectroscopic ellipsometry, and X-ray photoelectron spectroscopy. We took advantage of the native disulfide bridge of the oxytocin for anchoring the peptide to the Au surface, while preserving the metal-ion binding properties. Self-assembled oxytocin monolayer was used by electrochemical impedance spectroscopy for metal-ion sensing leading to subnanomolar sensitivities for zinc or copper ions.
Aerogel objects inspired by plant cell wall components and structures were fabricated using extrusion-based 3D printing at cryogenic temperatures. The printing process combines 3D printing with the alignment of rod-shaped nanoparticles through the freeze-casting of aqueous inks. We have named this method direct cryo writing (DCW) as it encompasses in a single processing step traditional directional freeze casting and the spatial fidelity of 3D printing. DCW is demonstrated with inks that are composed of an aqueous mixture of cellulose nanocrystals (CNCs) and xyloglucan (XG), which are the major building blocks of plant cell walls. Rapid fixation of the inks is achieved through tailored rheological properties and controlled directional freezing. Morphological evaluation revealed the role of ice crystal growth in the alignment of CNCs and XG. The structure of the aerogels changed from organized and tubular to disordered and flakey pores with an increase in XG content. The internal structure of the printed objects mimics the structure of various wood species and can therefore be used to create wood-like structures via additive manufacturing technologies using only renewable wood-based materials.
Aerogel objects inspired by plant cell wall components and structures were fabricated using extrusion-based 3D printing at cryogenic temperatures. The printing process combines 3D printing with the alignment of rod-shaped nanoparticles through the freeze-casting of aqueous inks. We have named this method direct cryo writing (DCW) as it encompasses in a single processing step traditional directional freeze casting and the spatial fidelity of 3D printing. DCW is demonstrated with inks that are composed of an aqueous mixture of cellulose nanocrystals (CNCs) and xyloglucan (XG), which are the major building blocks of plant cell walls. Rapid fixation of the inks is achieved through tailored rheological properties and controlled directional freezing. Morphological evaluation revealed the role of ice crystal growth in the alignment of CNCs and XG. The structure of the aerogels changed from organized and tubular to disordered and flakey pores with an increase in XG content. The internal structure of the printed objects mimics the structure of various wood species and can therefore be used to create wood-like structures via additive manufacturing technologies using only renewable wood-based materials.
We studied the direct electron transfer (DET) between glucose and electrogenerated AuCl4- catalysed by glucose oxidase (GOx) and gold nanoparticles (AuNPs) by scanning electrochemical microscopy (SECM). Well-defined AuNPs were prepared and attached onto an insulating surface. Studying the current transients of a gold microelectrode held within a few microns from the surface revealed that the AuNPs interacted with the GOx and were crucial for the DET from the glucose. We investigated very carefully the effect of pH and the size of the AuNPs on electron transfer. AuNPs of 16, 40 and 80 nm diameter were applied. The kinetics of electron transfer was analysed by the Michael-Menten kinetic mechanism. Interestingly, we found that the fastest DET was exhibited by the 40 nm AuNPs at pH 3 and 5. At higher pH, electron transfer was better catalysed by the 80 nm AuNPs. This was rationalized by the effect of the pH on the enzymatic structure and the charge of the AuNPs.
An acto-myosin contractile ring, which forms after anaphase onset and is highly regulated in time and space, mediates cytokinesis, the final step of mitosis. The chromosomal passenger complex (CPC), composed of Aurora-B kinase, INCENP, borealin and survivin (also known as BIRC5), regulates various processes during mitosis, including cytokinesis. It is not understood, however, how CPC regulates cytokinesis. We show that survivin binds to non-muscle myosin II (NMII), regulating its filament assembly. Survivin and NMII interact mainly in telophase, and Cdk1 regulates their interaction in a mitotic-phase-specific manner, revealing the mechanism for the specific timing of survivin-NMII interaction during mitosis. The survivin-NMII interaction is indispensable for cytokinesis, and its disruption leads to multiple mitotic defects. We further show that only the survivin homodimer binds to NMII, attesting to the biological importance for survivin homodimerization. We suggest a novel function for survivin in regulating the spatio-temporal formation of the acto-NMII contractile ring during cytokinesis and we elucidate the role of Cdk1 in regulating this process.This article has an associated First Person interview with the first author of the paper.
Directed-assembly by standing surface acoustic waves (SSAWs) only requires an acoustic contrast between particles and their surrounding medium. It is therefore highly attractive as this requirement is fulfilled by almost all dispersed systems. Previous studies utilizing SSAWs demonstrated mainly reversible microstructure arrangements from nanoparticles. The surface chemistry of colloids dramatically influences their tendency to aggregate and sinter; therefore, it should be possible to form permanent microstructures with intimate contact between nanoparticles by controlling this property. Dispersed silver nanoparticles in a microfluidic channel were exposed to SSAWs and reversibly accumulated at the pressure nodes. We show that addition of chloride ions that remove the polyacrylic capping of the nanoparticles trigger their sintering and the formation of stable conducting silver microstructures. Moreover, if the destabilizing ions are added prior to nanoparticle assembly while continuously streaming the dispersion through the acoustic aperture, the induced aggregation leads to formation of significantly thinner microstructures, which are (for the first time) unlimited in length by the acoustic apparatus. This new approach overcomes the discrepancy between the need for organic dispersants to prevent unwanted aggregation in the dispersion, and the end product's requirement for intimate contact between the colloidal particles.
This study examined disclosure strategies in cystic fibrosis (CF) and their psychosocial implications for adults. Disclosure styles were examined based on Corrigan and Lundin's (2001) model. In-depth qualitative interviews were conducted with 42 individuals diagnosed with CF from two CF clinics in Israel. Disclosure of CF is complex and involves multiple strategies. Two main themes regarding disclosure presented here are: (a) disclosure styles and their psychosocial implications, and (b) perceptions of the differences between previous and current disclosure styles. Of disclosure styles suggested by Corrigan and Lundin (2001), most participants were found to resort to secrecy, selective disclosure, and indiscriminate disclosure and very few resorted to avoidance or broadcasting. Disclosure was also dynamic, and individuals changed their disclosure styles during various stages of life and situations, in consideration of its benefits and costs. Decisions regarding whether and to what extent to disclose the illness were based on two processes: weighing the benefits and costs of disclosure and owning the decision to disclose. Professionals should partner with the patients to understand patients’ disclosure decisions and support them. Formal and informal support may assist individuals in making these decisions, helping them become aware of benefits and costs.
It is an open question whether aging-related changes throughout the brain are driven by a common factor or result from several distinct molecular mechanisms. Quantitative magnetic resonance imaging (qMRI) provides biophysical parametric measurements allowing for non-invasive mapping of the aging human brain. However, qMRI measurements change in response to both molecular composition and water content. Here, we present a tissue relaxivity approach that disentangles these two tissue components and decodes molecular information from the MRI signal. Our approach enables us to reveal the molecular composition of lipid samples and predict lipidomics measurements of the brain. It produces unique molecular signatures across the brain, which are correlated with specific gene-expression profiles. We uncover region-specific molecular changes associated with brain aging. These changes are independent from other MRI aging markers. Our approach opens the door to a quantitative characterization of the biological sources for aging, that until now was possible only post-mortem.
Alternative transportation fuels (ATFs) can reduce air pollution. However, the influence of conventional fuels—diesel and gasoline, and particularly ATFs on photochemical air pollution is not well-characterized, limiting assessments of ATFs and air quality. This is mainly due to frequent use of lumped chemical mechanisms by related atmospheric modeling. Here we hypothesized that applying a chemical mechanism that is specifically developed according to both emission fractions and photochemical ozone creation potential of volatile organic compounds (VOCs) is key to gaining reliable insights into the impact of transportation fuels on photochemistry. We used a heterogeneous chemical mechanism with 927 reactions and relatively detailed emission inventories to specifically meet the requirements for reliable simulation of the effect of exhaust emissions from vehicles fueled by selected model fuels—diesel, gasoline, and mixtures of 15% gasoline with 85% ethanol (E85) or 85% methanol (M85)—on photochemistry. These dispersion-box model simulations revealed a strong influence of atmospheric background balance between VOCs and nitrogen oxides (NOX = [NO] + [NO2]) on the impact of exhaust emissions on photochemistry, with higher tendency toward ozone (O3) formation or destruction for more VOC-limited or NOX-limited conditions, respectively. Accordingly, higher [NOX]/[VOC] exhaust emission, such as from diesel and M85, resulted in lower O3, not only locally but also downwind of the emission. This offers a new perspective and measure for transportation fuel assessment. Rapid conversion of O3 to hydroxyl and hydroperoxyl radicals downwind of the exhaust emission indicates the importance of simulating the impact of road transportation on photochemistry at high spatial and temporal resolution. Peroxyacetyl nitrate formation was more sensitive to VOC emission under VOC-limited conditions than to NOX emission under NOX-limited conditions. Secondary formaldehyde dominated over primary emitted formaldehyde several minutes after emission. These findings should be verified using a 3D modeling study under varying meteorological conditions.