Tau Aggregation.

Here we revisit tau protein aggregation at primary, secondary, tertiary and quaternary structures. In addition, the presence of non-aggregated tau protein, which has been recently discovered, is also commented on.

Adapted to Survive: Targeting Cancer Cells with BH3 Mimetics.

Unlabelled: A hallmark of cancer is cell death evasion, underlying suboptimal responses to chemotherapy, targeted agents, and immunotherapies. The approval of the antiapoptotic BCL2 antagonist venetoclax has finally validated the potential of targeting apoptotic pathways in patients with cancer. Nevertheless, pharmacologic modulators of cell death have shown markedly varied responses in preclinical and clinical studies.

Micromotor-in-Sponge Platform for Multicycle Large-Volume Degradation of Organic Pollutants.

The presence of organic pollutants in the environment is a global threat to human health and ecosystems due to their bioaccumulation and long-term persistence. Hereby a micromotor-in-sponge concept is presented that aims not only at pollutant removal, but towards an efficient in situ degradation by exploiting the synergy between the sponge hydrophobic nature and the rapid pollutant degradation promoted by the cobalt-ferrite (CFO) micromotors embedded at the sponge's core. Such a platform allows the use of extremely low fuel concentration (0.

Autonomous Treatment of Bacterial Infections Using Antimicrobial Micro- and Nanomotors.

The increasing resistance of bacteria to existing antibiotics constitutes a major public health threat globally. Most current antibiotic treatments are hindered by poor delivery to the infection site, leading to undesired off-target effects and drug resistance development and spread. Here, we describe micro- and nanomotors that effectively and autonomously deliver antibiotic payloads to the target area.

Loss of E-cadherin leads to Id2-dependent inhibition of cell cycle progression in metastatic lobular breast cancer.

Invasive lobular breast carcinoma (ILC) is characterized by proliferative indolence and long-term latency relapses. This study aimed to identify how disseminating ILC cells control the balance between quiescence and cell cycle re-entry. In the absence of anchorage, ILC cells undergo a sustained cell cycle arrest in G0/G1 while maintaining viability.

Phase irregularity: A conceptually simple and efficient approach to characterize electroencephalographic recordings from epilepsy patients.

The severe neurological disorder epilepsy affects almost 1% of the world population. For patients who suffer from pharmacoresistant focal-onset epilepsy, electroencephalographic (EEG) recordings are essential for the localization of the brain area where seizures start. Apart from the visual inspection of the recordings, quantitative EEG signal analysis techniques proved to be useful for this purpose.

Chronic use of cannabis might impair sensory error processing in the cerebellum through endocannabinoid dysregulation.

Chronic use of cannabis leads to both motor deficits and the downregulation of CB receptors (CBR) in the cerebellum. In turn, cerebellar damage is often related to impairments in motor learning and control. Further, a recent motor learning task that measures cerebellar-dependent adaptation has been shown to distinguish well between healthy subjects and chronic cannabis users.

Binding of anisotropic curvature-inducing proteins onto membrane tubes.

Bin/Amphiphysin/Rvs superfamily proteins and other curvature-inducing proteins have anisotropic shapes and anisotropically bend biomembranes. Here, we report how the anisotropic proteins bind the membrane tube and are orientationally ordered using mean-field theory including an orientation-dependent excluded volume. The proteins exhibit a second-order or first-order nematic transition with increasing protein density depending on the radius of the membrane tube.

Effectiveness of Direct Laser Interference Patterning and Peptide Immobilization on Endothelial Cell Migration for Cardio-Vascular Applications: An In Vitro Study.

Endothelial coverage of an exposed cardiovascular stent surface leads to the occurrence of restenosis and late-stent thrombosis several months after implantation. To overcome this difficulty, modification of stent surfaces with topographical or biochemical features may be performed to increase endothelial cells' (ECs) adhesion and/or migration. This work combines both strategies on cobalt-chromium (CoCr) alloy and studies the potential synergistic effect of linear patterned surfaces that are obtained by direct laser interference patterning (DLIP), coupled with the use of Arg-Gly-Asp (RGD) and Tyr-Ile-Gly-Ser-Arg (YIGSR) peptides.

Bringing lipidic lyotropic liquid crystal technology into biomedicine.

Liquid crystals (LCs), discovered more than 130 years ago, are now emerging in the field of biomedicine. This article highlights the recent uses of lipid lyotropic LCs in therapeutics delivery, imaging, and tissue engineering and invites the scientific community to continue exploring the design of more complex LCs.

Sustained local ionic homeostatic imbalance caused by calcification modulates inflammation to trigger heterotopic ossification.

Heterotopic ossification (HO) is a condition triggered by an injury leading to the formation of mature lamellar bone in extraskeletal soft tissues. Despite being a frequent complication of orthopedic and trauma surgery, brain and spinal injury, the etiology of HO is poorly understood. The aim of this study is to evaluate the hypothesis that a sustained local ionic homeostatic imbalance (SLIHI) created by mineral formation during tissue calcification modulates inflammation to trigger HO.

Ionic Combisomes: A New Class of Biomimetic Vesicles to Fuse with Life.

The construction of biomembranes that faithfully capture the properties and dynamic functions of cell membranes remains a challenge in the development of synthetic cells and their application. Here a new concept for synthetic cell membranes based on the self-assembly of amphiphilic comb polymers into vesicles, termed ionic combisomes (i-combisomes) is introduced. These combs consist of a polyzwitterionic backbone to which hydrophobic tails are linked by electrostatic interactions.

MEK and MCL-1 sequential inhibition synergize to enhance rhabdomyosarcoma treatment.

Targeted agents have emerged as promising molecules for cancer treatment, but most of them fail to achieve complete tumor regression or attain durable remissions due to tumor adaptations. We used dynamic BH3 profiling to identify targeted agents effectiveness and anti-apoptotic adaptations upon targeted treatment in rhabdomyosarcoma. We focused on studying the use of BH3 mimetics to specifically inhibit pro-survival BCL-2 family proteins, overwhelm resistance to therapy and prevent relapse.

Junctional epithelium and hemidesmosomes: Tape and rivets for solving the "percutaneous device dilemma" in dental and other permanent implants.

The percutaneous device dilemma describes etiological factors, centered around the disrupted epithelial tissue surrounding non-remodelable devices, that contribute to rampant percutaneous device infection. Natural percutaneous organs, in particular their extracellular matrix mediating the "device"/epithelium interface, serve as exquisite examples to inspire longer lasting long-term percutaneous device design. For example, the tooth's imperviousness to infection is mediated by the epithelium directly surrounding it, the junctional epithelium (JE).

Novel Biobased Epoxy Thermosets and Coatings from Poly(limonene carbonate) Oxide and Synthetic Hardeners.

In the area of coating development, it is extremely difficult to find a substitute for bisphenol A diglycidyl ether (DGEBA), the classical petroleum-based raw material used for the formulation of epoxy thermosets. This epoxy resin offers fast curing reaction with several hardeners and the best thermal and chemical resistance properties for applications in coatings and adhesive technologies. In this work, a new biobased epoxy, derived from poly(limonene carbonate) oxide (PLCO), was combined with polyetheramine and polyamineamide curing agents, offering a spectrum of thermal and mechanical properties, superior to DGEBA-based thermosets.

Permanently polarized hydroxyapatite, an outstanding catalytic material for carbon and nitrogen fixation.

Hydroxyapatite (HAp) is a well-known ceramic material widely used in the biomedical field. This review summarizes the very recent developments on permanently polarized HAp (pp-HAp), a HAp variety with tuned electrical properties that confer remarkable catalytic activity. pp-HAp is obtained by applying a thermal stimulation polarization process (TSP), which consists on a DC electric voltage of 500 V at 1000 °C, to previously sintered HAp.

Novel Decellularization Method for Tissue Slices.

Decellularization procedures have been developed and optimized for the entire organ or tissue blocks, by either perfusion of decellularizing agents through the tissue's vasculature or submerging large sections in decellularizing solutions. However, some research aims require the analysis of native as well as decellularized tissue slices side by side, but an optimal protocol has not yet been established to address this need. Thus, the main goal of this work was to develop a fast and efficient decellularization method for tissue slices-with an emphasis on lung-while attached to a glass slide.

Mycobacterial surface characters remodeled by growth conditions drive different tumor-infiltrating cells and systemic IFN-γ/IL-17 release in bladder cancer treatment.

The mechanism of action of intravesical BCG immunotherapy treatment for bladder cancer is not completely known, leading to misinterpretation of BCG-unresponsive patients, who have scarce further therapeutic options. BCG is grown under diverse culture conditions worldwide, which can impact the antitumor effect of BCG strains and could be a key parameter of treatment success. Here, BCG and the nonpathogenic were grown in four culture media currently used by research laboratories and BCG manufacturers: Sauton-A60, -G15 and -G60 and Middlebrook 7H10, and used as therapies in the orthotopic murine BC model.

Enzyme Purification Improves the Enzyme Loading, Self-Propulsion, and Endurance Performance of Micromotors.

Enzyme-powered micro- and nanomotors make use of biocatalysis to self-propel in aqueous media and hold immense promise for active and targeted drug delivery. Most (if not all) of these micro- and nanomotors described to date are fabricated using a commercially available enzyme, despite claims that some commercial preparations may not have a sufficiently high degree of purity for downstream applications. In this study, the purity of a commercial urease, an enzyme frequently used to power the motion of micro- and nanomotors, was evaluated and found to be impure.

Femtoliter Injection of ESCRT-III Proteins into Adhered Giant Unilamellar Vesicles.

The endosomal sorting complex required for transport (ESCRT) machinery mediates membrane fission reactions that exhibit a different topology from that observed in clathrin-coated vesicles. In all of the ESCRT-mediated events, the nascent vesicle buds away from the cytosol. However, ESCRT proteins are able to act upon membranes with different geometries.

Metabolomics and integrated network analysis reveal roles of endocannabinoids and large neutral amino acid balance in the ayahuasca experience.

There has been a renewed interest in the potential use of psychedelics for the treatment of psychiatric conditions. Nevertheless, little is known about the mechanism of action and molecular pathways influenced by ayahuasca use in humans. Therefore, for the first time, our study aims to investigate the human metabolomics signature after consumption of a psychedelic, ayahuasca, and its connection with both the psychedelic-induced subjective effects and the plasma concentrations of ayahuasca alkaloids.

Undetected Respiratory Depression in People with Opioid Use Disorder.

Background: Opioid-related deaths are increasing globally. Respiratory complications of opioid use and underlying respiratory disease in people with Opioid Use Disorder (OUD) are potential contributory factors. Individual variation in susceptibility to overdose is, however, incompletely understood.

Müller glia fused with adult stem cells undergo neural differentiation in human retinal models.

Background: Visual impairments are a critical medical hurdle to be addressed in modern society. Müller glia (MG) have regenerative potential in the retina in lower vertebrates, but not in mammals. However, in mice, in vivo cell fusion between MG and adult stem cells forms hybrids that can partially regenerate ablated neurons.

A Single-Molecule View at Nanoparticle Targeting Selectivity: Correlating Ligand Functionality and Cell Receptor Density.

Antibody-functionalized nanoparticles (NPs) are commonly used to increase the targeting selectivity toward cells of interest. At a molecular level, the number of functional antibodies on the NP surface and the density of receptors on the target cell determine the targeting interaction. To rationally develop selective NPs, the single-molecule quantitation of both parameters is highly desirable.