Structural and functional characterization of a histidylated liposome for mRNA delivery.

The development of lipid-based mRNA delivery systems has significantly facilitated recent advances in mRNA-based therapeutics. Liposomes, as the pioneering class of mRNA vectors, continue to lead in clinical trials. We previously developed a histidylated liposome that demonstrated efficient nucleic acid delivery.

Thermodynamic and kinetic study of palladium(II) complexation with 1-methyl-2-mercaptoimidazole (methimazole) and their importance for structural design of metallodrugs.

The acidobasic and complexing properties of 1-methyl-2-mercaptoimidazole (Methimazole, an anti-thyroid drug) were investigated. The pK 11.49 ± 0.

Limited Impact of Cannabidiol on Health-related Quality of Life of People With Long-term Controlled HIV: A Double-blind, Randomized, Controlled Trial.

Background: People with HIV (PWH) with undetectable HIV viral load still have an impaired health-related quality of life (HRQoL). Cannabidiol (CBD) is a nonintoxicating cannabis-derived cannabinoid that holds promise for the treatment of many ailments. In the present study, we tested whether oral CBD-rich medication could significantly improve PWH's HRQoL.

Dynamic BTB-domain filaments promote clustering of ZBTB proteins.

The formation of dynamic protein filaments contributes to various biological functions by clustering individual molecules together and enhancing their binding to ligands. We report such a propensity for the BTB domains of certain proteins from the ZBTB family, a large eukaryotic transcription factor family implicated in differentiation and cancer. Working with Xenopus laevis and human proteins, we solved the crystal structures of filaments formed by dimers of the BTB domains of ZBTB8A and ZBTB18 and demonstrated concentration-dependent higher-order assemblies of these dimers in solution.

Integrins regulate hERG1 dynamics by girdin-dependent Gαi3: signaling and modeling in cancer cells.

The hERG1 potassium channel is aberrantly over expressed in tumors and regulates the cancer cell response to integrin-dependent adhesion. We unravel a novel signaling pathway by which integrin engagement by the ECM protein fibronectin promotes hERG1 translocation to the plasma membrane and its association with β1 integrins, by activating girdin-dependent Gαi3 proteins and protein kinase B (Akt). By sequestering hERG1, β1 integrins make it avoid Rab5-mediated endocytosis, where unbound channels are degraded.

An adult Drosophila glioma model to highlight metabolic dysfunctions and evaluate the role of the serotonin 5-HT receptor as a potential therapeutic target.

Gliomas account for 50% of brain cancers and are therefore the most common brain tumors. Molecular alterations involved in adult gliomas have been identified and mainly affect tyrosine kinase receptors with amplification and/or mutation of the epidermal growth factor receptor (EGFR) and its associated signaling pathways. Several targeted therapies have been developed, but current treatments remain ineffective for glioblastomas, the most severe forms.

Comparative effects of various running exercise modalities on femoral bone quality in rats.

Background: It is now well established that physical exercise is an effective preventive method to reduce and treat certain chronic diseases, particularly musculoskeletal disorders. At the bone level, running exercise is well known for its positive effects on various parameters of bone quality. There is, however, no consensus regarding the effects of different running exercise modalities on bone quality.

Streamlining N-terminally anchored yeast surface display via structural insights into S. cerevisiae Pir proteins.

Surface display co-opts yeast's innate ability to embellish its cell wall with mannoproteins, thus converting the yeast's outer surface into a growing and self-sustaining catalyst. However, the efficient toolbox for converting the enzyme of interest into its surface-displayed isoform is currently lacking, especially if the isoform needs to be anchored to the cell wall near the isoform's N-terminus, e.g.

Structural insights into the regulation of the human E2∼SUMO conjugate through analysis of its stable mimetic.

Protein SUMOylation is a ubiquitylation-like post-translational modification (PTM) that is synthesized through an enzymatic cascade involving an E1 (SAE1:SAE2), an E2 (UBC9), and various E3 enzymes. In the final step of this process, the small ubiquitin-like modifier (SUMO) is transferred from the UBC9∼SUMO thioester onto a lysine residue of a protein substrate. This reaction can be accelerated by an E3 ligase.

OGG1 competitive inhibitors show important off-target effects by directly inhibiting efflux pumps and disturbing mitotic progression.

One of the most abundant DNA lesions induced by Reactive oxygen species (ROS) is 8-oxoG, a highly mutagenic lesion that compromises genetic instability when not efficiently repaired. 8-oxoG is specifically recognized by the DNA-glycosylase OGG1 that excises the base and initiates the Base Excision Repair pathway (BER). Furthermore, OGG1 has not only a major role in DNA repair but it is also involved in transcriptional regulation.

Confocal imaging of biomarkers at a single-cell resolution: quantifying 'living' in 3D-printable engineered living material based on Pluronic F-127 and yeast Saccharomyces cerevisiae.

Background: Engineered living materials (ELMs) combine living cells with non-living scaffolds to obtain life-like characteristics, such as biosensing, growth, and self-repair. Some ELMs can be 3D-printed and are called bioinks, and their scaffolds are mostly hydrogel-based. One such scaffold is polymer Pluronic F127, a liquid at 4 °C but a biocompatible hydrogel at room temperature.

Structural and functional determinants of the archaeal 8-oxoguanine-DNA glycosylase AGOG for DNA damage recognition and processing.

8-Oxoguanine (GO) is a major purine oxidation product in DNA. Because of its highly mutagenic properties, GO absolutely must be eliminated from DNA. To do this, aerobic and anaerobic organisms from the three kingdoms of life have evolved repair mechanisms to prevent its deleterious effect on genetic integrity.

Expression of the Human Serotonin 5-HT Receptor Rescues Phenotype Profile and Restores Dysregulated Biomarkers in a Glioma Model.

Gliomas are the most common primary brain tumors in adults. Significant progress has been made in recent years in identifying the molecular alterations involved in gliomas. Among them, an amplification/overexpression of the EGFR (Epidermal Growth Factor Receptor) proto-oncogene and its associated signaling pathways have been widely described.

Impact of Treadmill Interval Running on the Appearance of Zinc Finger Protein FHL2 in Bone Marrow Cells in a Rat Model: A Pilot Study.

Although the benefits of physical exercise to preserve bone quality are now widely recognized, the intimate mechanisms leading to the underlying cell responses still require further investigations. Interval training running, for instance, appears as a generator of impacts on the skeleton, and particularly on the progenitor cells located in the bone marrow. Therefore, if this kind of stimulus initiates bone cell proliferation and differentiation, the activation of a devoted signaling pathway by mechano-transduction seems likely.

In Situ Raman Spectroscopy Monitoring of Material Changes During Proton Irradiation.

Organic molecules are prime targets in the search for life on other planetary bodies in the Solar System. Understanding their preservation potential and detectability after ionic irradiation, with fluences potentially representing those received for several millions to billions of years at Mars or in interplanetary space, is a crucial goal for astrobiology research. In order to be able to perform in situ characterization of such organic molecules under ionic irradiation in the near future, a feasibility experiment was performed with polymer test samples to validate the optical configuration and the irradiation chamber geometry.

mRNA, a Revolution in Biomedicine.

The perspective of using messenger RNA (mRNA) as a therapeutic molecule first faced some uncertainties due to concerns about its instability and the feasibility of large-scale production. Today, given technological advances and deeper biomolecular knowledge, these issues have started to be addressed and some strategies are being exploited to overcome the limitations. Thus, the potential of mRNA has become increasingly recognized for the development of new innovative therapeutics, envisioning its application in immunotherapy, regenerative medicine, vaccination, and gene editing.

A near-infrared emitting MOF: controlled encapsulation of a fluorescein sensitizer at the time of crystal growth.

We report here a near-infrared (NIR) emitting lanthanide-based metal-organic framework (MOF) in which Yb are sensitized by fluorescein (FL) as a low energy absorbing chromophore (FL@CD-MOF-161). The unique design of CD-MOF-161 allows for the entrapment of FL molecules in its pores during the synthesis and crystal growth, ensuring the efficient loading and spreading of chromophores within the crystal volume.

Dissipation-driven selection of states in non-equilibrium chemical networks.

Life has most likely originated as a consequence of processes taking place in non-equilibrium conditions (e.g. in the proximity of deep-sea thermal vents) selecting states of matter that would have been otherwise unfavorable at equilibrium.

Non-coding RNAs: Emerging from the discovery to therapeutic applications.

The knowledge about non-coding RNAs (ncRNAs) is rapidly increasing with new data continuously emerging, regarding their diverse types, applications, and roles. Particular attention has been given to ncRNA with regulatory functions, which may have a critical role both in biological and pathological conditions. As a result of the diversity of ncRNAs and their ubiquitous involvement in several biologic processes, ncRNA started to be considered in the biomedical field, with immense potential to be exploited either as biomarkers or as therapeutic agents in certain pathologies.

Bambusuril Macrocycles as Mediators of Supramolecular Interactions: Application to the Europium Cage Helicate.

Herein, it is shown how bambusurils can be used for tuning and/or characterizing supramolecular systems. Indeed, the addition of bambusurils as anion scavengers to metal-mediated self-assemblies allows manipulation of the subtle equilibria in the given system. This is demonstrated for the case of the tetranuclear europium helical cage, which is well suited to different applications.

Kinetic theory of hyaluronan cleavage by bovine testicular hyaluronidase in standard and crowded environments.

In this paper, we introduce a comprehensive kinetic model describing the enzymatic cleavage of hyaluronan (HA) by bovine testicular hyaluronidase (BTH). Our theory focuses specifically on the late stage of the hydrolysis, where the concentrations of a limited number of oligomers may be determined experimentally with accuracy as functions of time. The present model was applied to fit different experimental sets of kinetic data collected by capillary electrophoresis at two HA concentrations and three concentrations of PEG crowder (0, 10, 17% w/w).

Dephasing-Assisted Macrospin Transport.

Transport phenomena are ubiquitous in physics, and it is generally understood that the environmental disorder and noise deteriorates the transfer of excitations. There are, however, cases in which transport can be enhanced by fluctuations. In the present work, we show, by means of micromagnetics simulations, that transport efficiency in a chain of classical macrospins can be greatly increased by an optimal level of dephasing noise.

Dimerization of Uracil in a Simulated Mars-like UV Radiation Environment.

The search for organic molecules at the surface of Mars is a key objective in astrobiology, given that many organic compounds are possible biosignatures and their presence is of interest with regard to the habitability of Mars. Current environmental conditions at the martian surface are harsh and affect the stability of organic molecules. For this reason, and because current and future Mars rovers collect samples from the upper surface layer, it is important to assess the fate of organic molecules under the conditions at the martian surface.

Ficoll as testing material for diffusion weighted imaging-quality assurance phantoms.

Purpose: The aim of this work is to test the use of aqueous solutions of Ficoll®**, a highly branched polymer displaying crowding properties, to build a phantom suitable for Diffusion Weighted Imaging (DWI) in Magnetic Resonance Imaging (MRI).

Methods: We developed a test object made of a cylindrical plastic container with a precise geometrical arrangement suitable for measuring several samples at the same time. The container was designed to host single vials with variable geometry and number, and to fit inside common commercial head coils for MRI scanners.