Topological Order in an Antiferomagnetic Tetratic

We study lattice melting in two dimensional antiferromagnets. We argue that, for strong enough magnetic interactions, single lattice dislocations are prohibitive due to magnetic frustration. This leads to a melting scenario in which a tetratic phase, composed of free dislocation pairs and bound disclinations, separates the solid from the liquid phases. We demonstrate this phase numerically in a system of hard spheres confined between parallel plates, where spins are represented by the the heights of the spheres. We find that, in the tetratic phase, the spins are as antiferromagnetically ordered as allowed by their spatial configuration

Structure and characterisation of hydroxyethylcellulose–silica nanoparticles

Functionalising nanoparticles with polymers has gained much interest in recent years, as it aids colloidal stability and manipulation of surface properties. Here, polymer-coated thiolated silica nanoparticles were synthesised by self-condensation of 3-mercaptopropyltrimethoxysilane in the presence of hydroxyethylcellulose. These nanoparticles were characterised by dynamic light scattering, small angle neutron scattering, Nanoparticle Tracking Analysis, Raman spectroscopy, FT-IR spectroscopy, thermogravimetric analysis, Ellman's assay, transmission electron microscopy and cryo-transmission electron microscopy. It was found that increasing the amount of hydroxyethylcellulose in the reaction mixture increased the nanoparticle size and reduced the number of thiol groups on their surface. Additionally, by utilising small angle neutron scattering and dynamic light scattering, it was demonstrated that higher concentrations of polymer in the reaction mixture (0.5–2% w/v) resulted in the formation of aggregates, whereby several silica nanoparticles are bridged together with macromolecules of hydroxyethylcellulose. A correlation was identified between the aggregate size and number of particles per aggregate based on size discrepancies observed between DLS and SANS measurements. This information makes it possible to control the size of aggregates during a simple one-pot synthesis; a prospect highly desirable in the design of potential drug delivery systems

Ferritin is secreted via 2 distinct nonclassical vesicular pathways

Ferritin turnover plays a major role in tissue iron homeostasis, and ferritin malfunction is associated with impaired iron homeostasis and neurodegenerative diseases. In most eukaryotes, ferritin is considered an intracellular protein that stores iron in a nontoxic and bioavailable form. In insects, ferritin is a classically secreted protein and plays a major role in systemic iron distribution. Mammalian ferritin lacks the signal peptide for classical endoplasmic reticulum–Golgi secretion but is found in serum and is secreted via a nonclassical lysosomal secretion pathway. This study applied bioinformatics and biochemical tools, alongside a protein trafficking mouse models, to characterize the mechanisms of ferritin secretion. Ferritin trafficking via the classical secretion pathway was ruled out, and a 2:1 distribution of intracellular ferritin between membrane-bound compartments and the cytosol was observed, suggesting a role for ferritin in the vesicular compartments of the cell. Focusing on nonclassical secretion, we analyzed mouse models of impaired endolysosomal trafficking and found that ferritin secretion was decreased by a BLOC-1 mutation but increased by BLOC-2, BLOC-3, and Rab27A mutations of the cellular trafficking machinery, suggesting multiple export routes. A 13-amino-acid motif unique to ferritins that lack the secretion signal peptide was identified on the BC-loop of both subunits and plays a role in the regulation of ferritin secretion. Finally, we provide evidence that secretion of iron-rich ferritin was mediated via the multivesicular body–exosome pathway. These results enhance our understanding of the mechanism of ferritin secretion, which is an important piece in the puzzle of tissue iron homeostasis

Engineering pH-Sensitive Stable Nanovesicles for Delivery of MicroRNA Therapeutics

MicroRNAs (miRNAs) are small non-coding endogenous RNAs, which are attracting a growing interest as therapeutic molecules due to their central role in major diseases. However, the transformation of these biomolecules into drugs is limited due to their unstability in the bloodstream, caused by nucleases abundantly present in the blood, and poor capacity to enter cells. The conjugation of miRNAs to nanoparticles (NPs) could be an effective strategy for their clinical delivery. Herein, the engineering of non-liposomal lipid nanovesicles, named quatsomes (QS), for the delivery of miRNAs and other small RNAs into the cytosol of tumor cells, triggering a tumor-suppressive response is reported. The engineered pH-sensitive nanovesicles have controlled structure (unilamellar), size (24 weeks), and are prepared by a green, GMP compliant, and scalable one-step procedure, which are all unavoidable requirements for the arrival to the clinical practice of NP based miRNA therapeutics. Furthermore, QS protect miRNAs from RNAses and when injected intravenously, deliver them into liver, lung, and neuroblastoma xenografts tumors. These stable nanovesicles with tunable pH sensitiveness constitute an attractive platform for the efficient delivery of miRNAs and other small RNAs with therapeutic activity and their exploitation in the clinics

Revisiting mouse peritoneal macrophages: heterogeneity, development, and function

Tissue macrophages play a crucial role in the maintenance of tissue homeostasis and also contribute to inflammatory and reparatory responses during pathogenic infection and tissue injury. the high heterogeneity of these macrophages is consistent with their adaptation to distinct tissue environments and specialization to develop niche-specific functions. Although peritoneal macrophages are one of the best-studied macrophage populations, recently it was demonstrated the co-existence of two subsets in mouse peritoneal cavity (PerC), which exhibit distinct phenotypes, functions, and origins. These macrophage subsets have been classified, according to their morphology, as large peritoneal macrophages (LPMs) and small peritoneal macrophages (SPMs). LPMs, the most abundant subset under steady state conditions, express high levels of F4/80 and low levels of class II molecules of the major histocompatibility complex (MHC). LPMs appear to be originated from embryogenic precursors, and their maintenance in PerC is regulated by expression of specific transcription factors and tissue-derived signals. Conversely, SPMs, a minor subset in unstimulated PerC, have a F4/80(low)MHC-IIhigh phenotype and are generated from bone-marrow-derived myeloid precursors. in response to infectious or inflammatory stimuli, the cellular composition of PerC is dramatically altered, where LPMs disappear and SPMs become the prevalent population together with their precursor, the inflammatory monocyte. SPMs appear to be the major source of inflammatory mediators in PerC during infection, whereas LPMs contribute for gut-associated lymphoid tissue-independent and retinoic acid-dependent IgA production by peritoneal B-1 cells. in the previous years, considerable efforts have been made to broaden our understanding of LPM and SPM origin, transcriptional regulation, and functional profile. This review addresses these issues, focusing on the impact of tissue-derived signals and external stimulation in the complex dynamics of peritoneal macrophage populations.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)INCTVUniv São Paulo, Inst Ciencias Biomed, Dept Imunol, BR-05508900 São Paulo, SP, BrazilUniversidade Federal de São Paulo, CTC Mol, São Paulo, SP, BrazilUniversidade Federal de São Paulo, Dept Ciencias Biol, São Paulo, SP, BrazilUniversidade Federal de São Paulo, CTC Mol, São Paulo, SP, BrazilUniversidade Federal de São Paulo, Dept Ciencias Biol, São Paulo, SP, BrazilFAPESP: 2013/16010-5FAPESP: 2013/07140-2Web of Scienc

Tumor Treating Fields (TTFields) demonstrate antiviral functions in vitro, and safety for application to COVID-19 patients in a pilot clinical study

Coronaviruses are the causative agents of several recent outbreaks, including the COVID-19 pandemic. One therapeutic approach is blocking viral binding to the host receptor. As binding largely depends on electrostatic interactions, we hypothesized possible inhibition of viral infection through application of electric fields, and tested the effectiveness of Tumor Treating Fields (TTFields), a clinically approved cancer treatment based on delivery of electric fields. In preclinical models, TTFields were found to inhibit coronavirus infection and replication, leading to lower viral secretion and higher cell survival, and to formation of progeny virions with lower infectivity, overall demonstrating antiviral activity. In a pilot clinical study (NCT04953234), TTFields therapy was safe for patients with severe COVID-19, also demonstrating preliminary effectiveness data, that correlated with higher device usage

Protection of construction pit for car-park building in Ljubljana

V diplomski nalogi je obravnavano varovanje gradbene jame za objekt parkirno garažne hiše v Ljubljani. Varovalna konstrukcija je bila izvedena s sidranimi slopi po tehnologiji injektiranja pod visokimi pritiski (jet grouting). Sidranje smo izvedli z začasnimi geotehničnimi sidri v enem ali dveh nivojih. V nalogi je podan pregled postopkov za izvedbo jet grouting slopov in začasnih geotehničnih sider po veljavnih standardih. Pozornost je posvečena načinom izvedbe, ki so uveljavljeni pri nas, in problemom, ki se pojavljajo zaradi odstopanja od zhatev tehnične regulative ali nezmožnosti upoštevanja le-te. To je delno posledica zastarele opreme in utečenih postopkov izvajanja del. Dodatno pa na to vplivajo tudi zahteve po čim cenejši izvedbi gradbenih del. V nalogi so predstavljene izkušnje pridobljene med izvedbo varovalne konstrukcije gradbene jame, rezultati kontrolnih preiskav in problemi, ki so se pojavili med izvedbo del, ter rešitve teh problemov. V fazi izvedbe varovalne konstrukcije iz jet grouting slopov smo največ pozornosti posvetili tehnologiji enofaznega postopka injektiranja in njeni učinkovitosti v danih razmerah. Pri izvedbi geotehničnih sider pa smo največ pozornosti posvetili vgradnji in napenjanju preskusnih sider. Na gradbišču nastali problemi so lahko tudi posledica nepopolne gradbene dokumentacije, vključno s starimi in pomanjkljivimi načrti sosednjih objektov. V nalogi je prav tako obravnavano reševanje problemov, povezanih z nepričakovano sestavo temeljnih tal. Ta je pomembno vplivala na težave in zamude pri izvedbi in nemoteno napredovanje del.The subject of this thesis is the execution construction pit for multi-storey car-park building in Ljubljana. The supporting structure was made with high pressure grouting (e.q jet grouting), and anchored with temporary ground anchors in one or two levels. An overview of jet grouting and temporary ground anchors procedures accoding to current standards is shown. A special attention is put on the currently valid execution of works in our country. We primarily examined the problems occurring due to the deviation from technical regulations or inability to stick to them, which may be the consequence of either old equipment or sticking to generally accepted procedures of the execution, as well as requirements for a cheaper execution. The thesis presents the description of experiences gained during the execution works, the results of control examinations, the problems that occurred during the execution and appropriate solutions. In the phase of the jet-grouting-piles execution, which were used as a supporting structure, the attention was on the technology of the single fluid system and its effectiveness in the ground, while with ground anchors the most attention was paid to ground anchor installation and. The problems occurring on the construction site are often result of an incomplete project documentation, often involving the old and incomplete documentation of neighbouring buildings. The solution of issues in relation to the unexpected ground conditions, which significantly delayed the execution of works, is examined