Synthesis of hydrogels from biomaterials and their potential application in tissue engineering.

In this study, a series of hydrogels were synthesized from chitosan(s) that was crosslinking with glutaraldehyde at different concentrations. Ascorbic acid in an acidic medium was used to facilitate non-covalent interactions. The chitosan(s) was obtained from shrimp cytoskeleton; while ascorbic acid was extracted from xoconostle juice. The hydrogel reaction was monitored by UV-vis spectroscopy (550 nm) to determine the reaction kinetics and reaction order at 60 °C. The hydrogels structures were characterized by NMR, FT-IR, HR-MS and SEM, while the degree of cross-linking was examined with TGA-DA. The extracellular matrices were obtained as stable hydrogels where reached maximum crosslinking was of 7 %, independent of glutaraldehyde quantity added. The rheological properties showed a behavior of weak gels and a dependence of crosslinking agent concentration on strength at different temperatures. The cytotoxicity assay showed that the gels had no adverse effects on cellular growth for all concentrations of glutaraldehyde.

Tribological Performance of a Paraffinic Base Oil Additive with Coated and Uncoated SiO2 Nanoparticles.

Electric vehicles (EVs) have emerged as a technology that can replace internal combustion vehicles and reduce greenhouse gas emissions. Therefore, it is necessary to develop novel low-viscosity lubricants that can serve as potential transmission fluids for electric vehicles. Thus, this work analyzes the influence of both SiO2 and SiO2-SA (coated with stearic acid) nanomaterials on the tribological behavior of a paraffinic base oil with an ISO VG viscosity grade of 32 and a 133 viscosity index. A traditional two-step process through ultrasonic agitation was utilized to formulate eight nanolubricants of paraffinic oil + SiO2 and paraffinic base oil + SiO2-SA with nanopowder mass concentrations ranging from 0.15 wt% to 0.60 wt%. Visual control was utilized to investigate the stability of the nanolubricants. An experimental study of different properties (viscosity, viscosity index, density, friction coefficient, and wear) was performed. Friction analyses were carried out in pure sliding contacts at 393.15 K, and a 3D optical profilometer was used to quantify the wear. The friction results showed that, for the SiO2-SA nanolubricants, the friction coefficients were much lower than those obtained with the neat paraffinic base oil. The optimal nanoparticle mass concentration was 0.60 wt% SiO2-SA, with which the friction coefficient decreased by around 43%. Regarding wear, the greatest decreases in width, depth, and area were also found with the addition of 0.60 wt% SiO2-SA; thus, reductions of 21, 22, and 54% were obtained, respectively, compared with the neat paraffinic base oil.

miR-519a-3p, found to regulate cellular prion protein during Alzheimer's disease pathogenesis, as a biomarker of asymptomatic stages.

Clinical relevance of miRNAs as biomarkers is growing due to their stability and detection in biofluids. In this, diagnosis at asymptomatic stages of Alzheimer's disease (AD) remains a challenge since it can only be made at autopsy according to Braak NFT staging. Achieving the objective of detecting AD at early stages would allow possible therapies to be addressed before the onset of cognitive impairment. Many studies have determined that the expression pattern of some miRNAs is dysregulated in AD patients, but to date, none has been correlated with downregulated expression of cellular prion protein (PrPC) during disease progression. That is why, by means of cross studies of miRNAs up-regulated in AD with in silico identification of potential miRNAs-binding to 3'UTR of human PRNP gene, we selected miR-519a-3p for our study. Then, in vitro experiments were carried out in two ways. First, we validated miR-519a-3p target on 3'UTR-PRNP, and second, we analyzed the levels of PrPC expression after using of mimic technology on cell culture. In addition, RT-qPCR was performed to analyzed miR-519a-3p expression in human cerebral samples of AD at different stages of disease evolution. Additionally, samples of other neurodegenerative diseases such as other non-AD tauopathies and several synucleinopathies were included in the study. Our results showed that miR-519a-3p overlaps with PRNP 3'UTR in vitro and promotes downregulation of PrPC. Moreover, miR-519a-3p was found to be up-regulated exclusively in AD samples from stage I to VI, suggesting its potential use as a novel label of preclinical stages of the disease.

Machine-Learning-Accelerated Simulations for the Design of Airbag Constrained by Obstacles at Rest.

Predicting airbag deployment geometries is an important task for airbag and vehicle designers to meet safety standards based on biomechanical injury risk functions. This prediction is also an extraordinarily complex problem given the number of disciplines and their interactions. State-of-the-art airbag deployment geometry simulations (including time history) entail large, computationally expensive numerical methods such as finite element analysis (FEA) and computational fluid dynamics (CFD), among others. This complexity results in exceptionally large simulation times, making thorough exploration of the design space prohibitive. This paper proposes new parametric simulation models which drastically accelerate airbag deployment geometry predictions while maintaining the accuracy of the airbag deployment geometry at reasonable levels; these models, called herein machine learning (ML)-accelerated models, blend physical system modes with data-driven techniques to accomplish fast predictions within a design space defined by airbag and impactor parameters. These ML-accelerated models are evaluated with virtual test cases of increasing complexity: from airbag deployments against a locked deformable obstacle to airbag deployments against free rigid obstacles; the dimension of the tested design spaces is up to six variables. ML training times are documented for completeness; thus, airbag design explorers or optimization engineers can assess the full budget for ML-accelerated approaches including training. In these test cases, the ML-accelerated simulation models run three orders of magnitude faster than the high-fidelity multi-physics methods, while accuracies are kept within reasonable levels within the design space.

Tritordeum, a hybrid cereal with a highly tricin-enriched lignin.

The lignin from tritordeum straw, a hybrid cereal from crossbreeding of durum wheat and wild barley, was isolated and chemically characterized. Its composition and structure were studied by analytical pyrolysis (Py-GC/MS), nuclear magnetic resonance spectroscopy (NMR), Derivatization Followed by Reductive Cleavage (DFRC) method, and gel permeation chromatography (GPC). The data revealed an enrichment of guaiacyl (G) units (H:G:S of 3:61:36), which had a significant impact on the distribution of inter-unit linkages. The predominant linkages were the ß-O-4' alkyl-aryl ethers (78 % of all linkages), with substantial proportions of condensed linkages such as phenylcoumarans (11 %), resinols (4 %), spirodienones (4 %), and dibenzodioxocins (2 %). Moreover, DFRC revealed that tridordeum straw lignin was partly acylated at the γ-OH with both acetates and p-coumarates. Acetates were principally attached to G-units, whereas p-coumarates were predominantly attached to S-units. Furthermore, and more importantly, tritordeum lignin incorporates remarkable amounts of a valuable flavone, tricin, exceeding 30 g per kilogram of straw. Given the diverse industrial applications associated with this high-value molecule, tritordeum straw emerges as a promising and sustainable resource for its extraction.

Medical grade 3D printable bioabsorbable PLDL/Mg and PLDL/Zn composites for biomedical applications.

Medical grade PLDL, PLDL/Mg and PLDL/Zn filaments were manufactured by a dual extrusion method and used to prepare coupons and scaffolds with controlled porosity by fused filament fabrication. The mechanical properties, degradation mechanisms and biological performance were carefully analyzed. It was found that the presence of 4 vol.% of Mg and Zn particles did not substantially modify the mechanical properties but accelerated the degradation rate of PLDL. Moreover, the acidification of the pH due to degradation of the PLDL was reduced in the presence of metallic particles. Finally, cell adhesion and proliferation were excellent in the medical grade PLDL as well as in the polymer/metal composites. These results demonstrate the potential of bioabsorbable metal/polymer composites to tailor the mechanical properties, degradation rate and biocompatibility for specific clinical applications.

Neurofibromatosis Type I Presenting with Incomplete Ileal Volvulus in a Pediatric Patient.

BACKGROUND Neurofibromatosis 1 is a neurocutaneous disorder with multisystemic manifestations. When patients are lacking overt cutaneous manifestations, diagnosis may be delayed and may complicate diagnosis and management of atypical presentations of this disease. It is thus important to strive to obtain relevant and/or complete history to arrive at the appropriate diagnosis. Furthermore, maintaining an index of suspicion in cases of vague abdominal pain may guide the clinician in establishing the correct diagnosis of mesenteric plexiform neurofibroma in the setting of known/presumed neurofibromatosis 1 patients presenting with acute and/or chronic vague abdominal symptoms. CASE REPORT This is a case of a teenage boy who presented with acute, vague abdominal pain over a period of 2 weeks. Laboratory tests and physical exam findings in primary and secondary care settings were unremarkable, and thus the patient was discharged home only to continue with abdominal pain, thus seeking additional medical care. After admission to our facility and exhaustive history taking, physical examination, and imaging, a prospective diagnosis of neurofibromatosis with mesenteric neurofibroma was made. Upon surgical exploration, a mesenteric mass with corresponding volvulized, ischemic small bowel was removed. Histopathology confirmed a plexiform neurofibroma. The patient recovered adequately and was discharged home without complications. CONCLUSIONS This case highlights the importance of exhaustive history taking to obtain an accurate diagnosis as well as the importance of a high index of clinical suspicion for mesenteric neurofibromatosis in patients with presumed or known neurofibromatosis and presenting with vague abdominal symptoms.

Injury-induced activation of the endocannabinoid system promotes axon regeneration.

Regeneration after a peripheral nerve injury still remains a challenge, due to the limited regenerative potential of axons after injury. While the endocannabinoid system (ECS) has been widely studied for its neuroprotective and analgesic effects, its role in axonal regeneration and during the conditioning lesion remains unexplored. In this study, we observed that a peripheral nerve injury induces axonal regeneration through an increase in the endocannabinoid tone. We also enhanced the regenerative capacity of dorsal root ganglia (DRG) neurons through the inhibition of endocannabinoid degradative enzyme MAGL or a CB1R agonist. Our results suggest that the ECS, via CB1R and PI3K-pAkt pathway activation, plays an important role in promoting the intrinsic regenerative capacity of sensory neurons after injury.

Variations in the composition and structure of the lignins of oat (Avena sativa L.) straws according to variety and planting season.

The differences in the composition and structure of the lignins from straws of different oat (Avena sativa L.) varieties, planted in two seasons (winter and spring), were studied in detail by different analytical techniques such as pyrolysis coupled to gas chromatography-mass spectrometry (Py-GC/MS), two-dimensional nuclear magnetic resonance (2D-NMR), derivatization followed by reductive cleavage (DFRC), and gel permeation chromatography (GPC). Overall, the analyses revealed that oat straw lignins were enriched in guaiacyl (G; 50-56 %) and syringyl (S; 39-44 %) units, with relatively lower amounts of p-hydroxyphenyl (H; 4-6 %) units. The lignins also incorporated significant quantities of p-coumarates (8-14 % of total lignin units), which are acylating the γ-OH of the lignin side chains, and predominantly over the S units. Furthermore, oat straw lignins also incorporated considerable amounts of the flavone tricin (5-12 % of total lignin units). Interestingly, this study revealed that the lignin content and composition of the oat straws vary with genotype and planting season. Since p-coumarates and tricin are high-value aromatic compounds especially attractive from a biorefinery point of view, the information disclosed here is highly relevant to plant breeding programs aimed at developing functional foods and lignin modifications for improved biorefinery applications.

Structural Characterization of the Milled-Wood Lignin Isolated from Sweet Orange Tree (Citrus sinensis) Pruning Residue.

The pruning of sweet orange trees (Citrus sinensis) generates large amounts of lignocellulosic residue. Orange tree pruning (OTP) residue presents a significant lignin content (21.2%). However, there are no previous studies describing the structure of the native lignin in OTPs. In the present work, the "milled-wood lignin" (MWL) was extracted from OTPs and examined in detail via gel permeation chromatography (GPC), pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS), and two-dimensional nuclear magnetic resonance (2D-NMR). The results indicated that the OTP-MWL was mainly composed of guaiacyl (G) units, followed by syringyl (S) units and minor amounts of p-hydroxyphenyl (H) units (H:G:S composition of 1:62:37). The predominance of G-units had a strong influence on the abundance of the different linkages; therefore, although the most abundant linkages were ß-O-4' alkyl-aryl ethers (70% of total lignin linkages), the lignin also contained significant amounts of phenylcoumarans (15%) and resinols (9%), as well as other condensed linkages such as dibenzodioxocins (3%) and spirodienones (3%). The significant content of condensed linkages will make this lignocellulosic residue more recalcitrant to delignification than other hardwoods with lower content of these linkages.

Deregulated Transcription and Proteostasis in Adult mapt Knockout Mouse.

Transcriptomics and phosphoproteomics were carried out in the cerebral cortex of B6.Cg-Mapttm1(EGFP)Klt (tau knockout: tau-KO) and wild-type (WT) 12 month-old mice to learn about the effects of tau ablation. Compared with WT mice, tau-KO mice displayed reduced anxiety-like behavior and lower fear expression induced by aversive conditioning, whereas recognition memory remained unaltered. Cortical transcriptomic analysis revealed 69 downregulated and 105 upregulated genes in tau-KO mice, corresponding to synaptic structures, neuron cytoskeleton and transport, and extracellular matrix components. RT-qPCR validated increased mRNA levels of col6a4, gabrq, gad1, grm5, grip2, map2, rab8a, tubb3, wnt16, and an absence of map1a in tau-KO mice compared with WT mice. A few proteins were assessed with Western blotting to compare mRNA expression with corresponding protein levels. Map1a mRNA and protein levels decreased. However, ß-tubulin III and GAD1 protein levels were reduced in tau-KO mice. Cortical phosphoproteomics revealed 121 hypophosphorylated and 98 hyperphosphorylated proteins in tau-KO mice. Deregulated phosphoproteins were categorized into cytoskeletal (n = 45) and membrane proteins, including proteins of the synapses and vesicles, myelin proteins, and proteins linked to membrane transport and ion channels (n = 84), proteins related to DNA and RNA metabolism (n = 36), proteins connected to the ubiquitin-proteasome system (UPS) (n = 7), proteins with kinase or phosphatase activity (n = 21), and 22 other proteins related to variegated pathways such as metabolic pathways, growth factors, or mitochondrial function or structure. The present observations reveal a complex altered brain transcriptome and phosphoproteome in tau-KO mice with only mild behavioral alterations.

Biomimetic oxidative copolymerization of hydroxystilbenes and monolignols.

Hydroxystilbenes are a class of polyphenolic compounds that behave as lignin monomers participating in radical coupling reactions during the lignification. Here, we report the synthesis and characterization of various artificial copolymers of monolignols and hydroxystilbenes, as well as low-molecular-mass compounds, to obtain the mechanistic insights into their incorporation into the lignin polymer. Integrating the hydroxystilbenes, resveratrol and piceatannol, into monolignol polymerization in vitro, using horseradish peroxidase to generate phenolic radicals, produced synthetic lignins [dehydrogenation polymers (DHPs)]. Copolymerization of hydroxystilbenes with monolignols, especially sinapyl alcohol, by in vitro peroxidases notably improved the reactivity of monolignols and resulted in substantial yields of synthetic lignin polymers. The resulting DHPs were analyzed using two-dimensional NMR and 19 synthesized model compounds to confirm the presence of hydroxystilbene structures in the lignin polymer. The cross-coupled DHPs confirmed both resveratrol and piceatannol as authentic monomers participating in the oxidative radical coupling reactions during polymerization.

Thioxanthenone-based derivatives as multitarget therapeutic leads for Alzheimer's disease.

A set of twenty-five thioxanthene-9-one and xanthene-9-one derivatives, that were previously shown to inhibit cholinesterases (ChEs) and amyloid ß (Aß40) aggregation, were evaluated for the inhibition of tau protein aggregation. All compounds exhibited a good activity, and eight of them (5-8, 10, 14, 15 and 20) shared comparable low micromolar inhibitory potency versus Aß40 aggregation and human acetylcholinesterase (AChE), while inhibiting human butyrylcholinesterase (BChE) even at submicromolar concentration. Compound 20 showed outstanding biological data, inhibiting tau protein and Aß40 aggregation with IC50 = 1.8 and 1.3 µM, respectively. Moreover, at 0.1-10 µM it also exhibited neuroprotective activity against tau toxicity induced by okadoic acid in human neuroblastoma SH-SY5Y cells, that was comparable to that of estradiol and PD38. In preliminary toxicity studies, these interesting results for compound 20 are somewhat conflicting with a narrow safety window. However, compound 10, although endowed with a little lower potency for tau and Aß aggregation inhibition additionally demonstrated good inhibition of ChEs and rather low cytotoxicity. Compound 4 is also worth of note for its high potency as hBChE inhibitor (IC50 = 7 nM) and for the three order of magnitude selectivity versus hAChE. Molecular modelling studies were performed to explain the different behavior of compounds 4 and 20 towards hBChE. The observed balance of the inhibitory potencies versus the relevant targets indicates the thioxanthene-9-one derivatives as potential MTDLs for AD therapy, provided that the safety window will be improved by further structural variations, currently under investigation.

Efficacy and safety of the extraction of cardiostimulation leads using a mechanical dissection tool. A single center experience.

BACKGROUND: The percutaneous extraction of endovascular cardiostimulation and defibrillation leads is the most frequent technique nowadays. The tools used today must guarantee the success of the procedure, with the minimum of complications. Our objective was to analyze the safety and efficacy of lead extraction using the Evolution mechanical dissection tool (Cook Medical, USA). METHODS: A retrospective study was carried out in a total of 826 consecutive patients from October 2009 to December 2018 who underwent the procedure with the Evolution mechanical dissection tool. Preoperative study included complete blood tests, echocardiogram, and chest X-ray. The procedures were performed in the operating room, under general anesthesia and echocardiographic control. RESULTS: A total of 1227 leads were extracted with a mean chronicity of 10.3 ± 5.1 years. Clinical success (CS) rate was 99.7%. A total of 16 (1.9%) complications occurred, 2 (0.24%) were major complications and 14 (1.7%) were minor complications. There was no operative mortality. There was no statistically significant relationship between implant chamber and complete efficacy. The complete extraction was achieved in all left ventricular leads, in 762 of 774 (98.45%) of right ventricular lead removal, and in 330 of 334 (98.8%) of right atrial leads (p = .31). CONCLUSION: In our experience, percutaneous extraction of intravenous leads via the use of the Evolution tool (Cook Medical, USA), is a very effective and safe technique that offers low morbidity and mortality.

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.

Peripheral CB1 receptor blockade acts as a memory enhancer through a noradrenergic mechanism.

Peripheral inputs continuously shape brain function and can influence memory acquisition, but the underlying mechanisms have not been fully understood. Cannabinoid type-1 receptor (CB1R) is a well-recognized player in memory performance, and its systemic modulation significantly influences memory function. By assessing low arousal/non-emotional recognition memory in mice, we found a relevant role of peripheral CB1R in memory persistence. Indeed, the peripherally-restricted CB1R specific antagonist AM6545 showed significant mnemonic effects that were occluded in adrenalectomized mice, and after peripheral adrenergic blockade. AM6545 also transiently impaired contextual fear memory extinction. Vagus nerve chemogenetic inhibition reduced AM6545-induced mnemonic effect. Genetic CB1R deletion in dopamine ß-hydroxylase-expressing cells enhanced recognition memory persistence. These observations support a role of peripheral CB1R modulating adrenergic tone relevant for cognition. Furthermore, AM6545 acutely improved brain connectivity and enhanced extracellular hippocampal norepinephrine. In agreement, intra-hippocampal ß-adrenergic blockade prevented AM6545 mnemonic effects. Altogether, we disclose a novel CB1R-dependent peripheral mechanism with implications relevant for lengthening the duration of non-emotional memory.

Dysregulated Protein Phosphorylation as Main Contributor of Granulovacuolar Degeneration at the First Stages of Neurofibrillary Tangles Pathology.

The hippocampus of cases with neurofibrillary tangles (NFT) pathology classified as stages I-II, III-IV, and V-VI without comorbidities, and middle-aged (MA) individuals with no NFT pathology, were examined to learn about the composition of granulovacuolar degeneration (GVD). Our results confirm the presence of CK1-δ, p38-P Thr180/Tyr182, SAPK/JNK-P Thr183/Thr185, GSK-3α/ß-P Tyr279/Tyr216, and GSK-3ß Ser9 in the cytoplasmic granules in a subset of neurons of the CA1 and CA2 subfields of the hippocampus. Also, we identify the presence of PKA α/ß-P Thr197, SRC-P Tyr416, PAK1-P Ser199/Ser204, CAMK2A-P Tyr197, and PKCG-P Thr655 in cytoplasmic granules in cases with NFT pathology, but not in MA cases. Our results also confirm the presence of ß-catenin-P Ser45/Thr41, IREα-P Ser274, eIF2α-P Ser51, TDP-43-P Ser403-404 (but absent TDP-43), and ubiquitin in cytoplasmic granules. Other components of the cytoplasmic granules are MAP2-P Thr1620/1623, MAP1B-P Thr1265, ADD1-P Ser726, and ADD1/ADD1-P Ser726/Ser713, in addition to several tau species including 3Rtau, 4Rtau, and tau-P Ser262. The analysis of GVD at progressive stages of NFT pathology reveals the early appearance of phosphorylated kinases and proteins in cytoplasmic granules at stages I-II, before the appearance of pre-tangles and NFTs. Most of these granules are not surrounded by LAMP1-positive membranes. Markers of impaired ubiquitin-protesome system, abnormal reticulum stress response, and altered endocytic and autophagic pathways occur in a subpopulation of neurons containing cytoplasmic granules, and they appear later. These observations suggest early phosphorylation of kinases leading to their activation, and resulting in the abnormal phosphorylation of various substrates, including tau, as a main alteration at the first stages of GVD.

Common and Specific Marks of Different Tau Strains Following Intra-Hippocampal Injection of AD, PiD, and GGT Inoculum in hTau Transgenic Mice.

Heterozygous hTau mice were used for the study of tau seeding. These mice express the six human tau isoforms, with a high predominance of 3Rtau over 4Rtau. The following groups were assessed: (i) non-inoculated mice aged 9 months (n = 4); (ii) Alzheimer's Disease (AD)-inoculated mice (n = 4); (iii) Globular Glial Tauopathy (GGT)-inoculated mice (n = 4); (iv) Pick's disease (PiD)-inoculated mice (n = 4); (v) control-inoculated mice (n = 4); and (vi) inoculated with vehicle alone (n = 2). AD-inoculated mice showed AT8-immunoreactive neuronal pre-tangles, granular aggregates, and dots in the CA1 region of the hippocampus, dentate gyrus (DG), and hilus, and threads and dots in the ipsilateral corpus callosum. GGT-inoculated mice showed unique or multiple AT8-immunoreactive globular deposits in neurons, occasionally extended to the proximal dendrites. PiD-inoculated mice showed a few loose pre-tangles in the CA1 region, DG, and cerebral cortex near the injection site. Coiled bodies were formed in the corpus callosum in AD-inoculated mice, but GGT-inoculated mice lacked globular glial inclusions. Tau deposits in inoculated mice co-localized active kinases p38-P and SAPK/JNK-P, thus suggesting active phosphorylation of the host tau. Tau deposits were absent in hTau mice inoculated with control homogenates and vehicle alone. Deposits in AD-inoculated hTau mice contained 3Rtau and 4Rtau; those in GGT-inoculated mice were mainly stained with anti-4Rtau antibodies, but a small number of deposits contained 3Rtau. Deposits in PiD-inoculated mice were stained with anti-3Rtau antibodies, but rare neuronal, thread-like, and dot-like deposits showed 4Rtau immunoreactivity. These findings show that tau strains produce different patterns of active neuronal seeding, which also depend on the host tau. Unexpected 3Rtau and 4Rtau deposits after inoculation of homogenates from 4R and 3R tauopathies, respectively, suggests the regulation of exon 10 splicing of the host tau during the process of seeding, thus modulating the plasticity of the cytoskeleton.

Microstructure and Electrical Conductivity of Cement Paste Reinforced with Different Types of Carbon Nanotubes.

Over the last few years, the addition of small amounts of carbon nanotubes (CNTs) to construction materials has become of great interest, since it enhances some of the mechanical, electrical and thermal properties of the cement. In this sense, single-walled and multi-walled carbon nanotubes (SWCNTs and MWCNTs, respectively) can be incorporated into cement to achieve the above-mentioned improved features. Thus, the current study presents the results of the addition of SWCNTs and MWCNTs on the microstructure and the physical properties of the cement paste. Density was measured through He pycnometry and the mass change was studied by thermogravimetric analysis (TGA). The microstructure and the phases were analyzed using scanning electron microscopy (SEM) and X-ray diffraction (XRD). Finally, the electrical conductivity for different CNT concentrations was measured, and an exponential increase of the conductivity with concentration was observed. This last result opens the possibility for these materials to be used in a high variety of fields, such as space intelligent systems with novel electrical and electronic applications.

Towards a Mechanistic Model of Tau-Mediated Pathology in Tauopathies: What Can We Learn from Cell-Based In Vitro Assays?

Tauopathies are a group of neurodegenerative diseases characterized by the hyperphosphorylation and deposition of tau proteins in the brain. In Alzheimer's disease, and other related tauopathies, the pattern of tau deposition follows a stereotypical progression between anatomically connected brain regions. Increasing evidence suggests that tau behaves in a "prion-like" manner, and that seeding and spreading of pathological tau drive progressive neurodegeneration. Although several advances have been made in recent years, the exact cellular and molecular mechanisms involved remain largely unknown. Since there are no effective therapies for any tauopathy, there is a growing need for reliable experimental models that would provide us with better knowledge and understanding of their etiology and identify novel molecular targets. In this review, we will summarize the development of cellular models for modeling tau pathology. We will discuss their different applications and contributions to our current understanding of the "prion-like" nature of pathological tau.