Tau Exon 10 Inclusion by PrPC through Downregulating GSK3β Activity

Tau protein is largely responsible for tauopathies, including Alzheimer’s disease (AD), where it accumulates in the brain as insoluble aggregates. Tau mRNA is regulated by alternative splicing, and inclusion or exclusion of exon 10 gives rise to the 3R and 4R isoforms respectively, whose balance is physiologically regulated. In this sense, one of the several factors that regulate alternative splicing of tau is GSK3β, whose activity is inhibited by the cellular prion protein (PrP^C), which has different physiological functions in neuroprotection and neuronal differentiation. Moreover, a relationship between PrP^C and tau expression levels has been reported during AD evolution. For this reason, in this study we aimed to analyze the role of PrP^C and the implication of GSK3β in the regulation of tau exon 10 alternative splicing. We used AD human samples and mouse models of PrP^C ablation and tau overexpression. In addition, we used primary neuronal cultures to develop functional studies. Our results revealed a paralleled association between PrP^C expression and tau 4R isoforms in all models analyzed. In this sense, reduction or ablation of PrP^C levels induces an increase in tau 3R/4R balance. More relevantly, our data points to GSK3β activity downstream from PrP^C in this phenomenon. Our results indicate that PrP^C plays a role in tau exon 10 inclusion through the inhibitory capacity of GSK3β.     

Microencapsulated Bifidobacterium bifidum and Lactobacillus gasseri in Combination with Quercetin Inhibit Colorectal Cancer Development in ApcMin/+ Mice

Recent studies have suggested that flavonoids such as quercetin and probiotics such as Bifidobacterium bifidum (Bf) and Lactobacillus gasseri (Lg) could play a relevant role in inhibiting colon cancer cell growth. Our study investigated the role of dietary supplementation with microencapsulated probiotics (Bf and Lg) along with quercetin in the development of mouse colorectal cancer (CRC). Methods: Adenomatous polyposis coli/multiple intestinal neoplasia (Apc^Min/+) mice were fed a standard diet or the same diet supplemented with microencapsulated probiotics (Bf and Lg strains, 10⁷ CFU/100 g food) or both probiotics strains plus microencapsulated quercetin (15 mg/100 g food) for 73 days. Changes in body and organ weights, energy metabolism, intestinal microbiota, and colon tissue were determined. The expression of genes related to the Wnt pathway was also analyzed in colon samples. Results: Dietary supplementation with microencapsulated probiotics or microencapsulated probiotics plus quercetin reduced body weight loss and intestinal bleeding in Apc^Min/+ mice. An improvement in energy expenditure was observed after 8 weeks but not after 10 weeks of treatment. A supplemented diet with microencapsulated Bf and Lg reduced the number of aberrant crypt foci (ACF) and adenomas by 45% and 60%, respectively, whereas the supplementation with Bf, Lg and quercetin decreased the number of ACF and adenomas by 57% and 80%, respectively. Microencapsulated Bf and Lg in combination with quercetin could exert inhibition of the canonical Wnt/β-catenin signaling pathway in the colon of Apc^Min/+ mice Conclusions: The administration of microencapsulated Bf and Lg, individually or in combination with quercetin, inhibits the CRC development in Apc^Min/+ mice.     

Syndecan-1 Depletion Has a Differential Impact on Hyaluronic Acid Metabolism and Tumor Cell Behavior in Luminal and Triple-Negative Breast Cancer Cells

Glycosaminoglycans (GAGs) and proteoglycans (PGs) are major components of the glycocalyx. The secreted GAG and CD44 ligand hyaluronic acid (HA), and the cell surface PG syndecan-1 (Sdc-1) modulate the expression and activity of cytokines, chemokines, growth factors, and adhesion molecules, acting as critical regulators of tumor cell behavior. Here, we studied the effect of Sdc-1 siRNA depletion and HA treatment on hallmark processes of cancer in breast cancer cell lines of different levels of aggressiveness. We analyzed HA synthesis, and parameters relevant to tumor progression, including the stem cell phenotype, Wnt signaling constituents, cell cycle progression and apoptosis, and angiogenic markers in luminal MCF-7 and triple-negative MDA-MB-231 cells. Sdc-1 knockdown enhanced HAS-2 synthesis and HA binding in MCF-7, but not in MDA-MB-231 cells. Sdc-1-depleted MDA-MB-231 cells showed a reduced CD24-/CD44+ population. Furthermore, Sdc-1 depletion was associated with survival signals in both cell lines, affecting cell cycle progression and apoptosis evasion. These changes were linked to the altered expression of KLF4, MSI2, and miR-10b and differential changes in Erk, Akt, and PTEN signaling. We conclude that Sdc-1 knockdown differentially affects HA metabolism in luminal and triple-negative breast cancer model cell lines and impacts the stem phenotype, cell survival, and angiogenic factors.     

Direct-Ink-Writing of Electroactive Polymers for Sensing and Energy Storage Applications

Considering the high levels of materials used in the fields of electronics and energy storage systems, it is increasingly necessary to take into consideration environmental impact. Thus, it is important to develop devices based on environmentally friendlier materials and/or processes, such as additive manufacturing techniques. In this work, poly(vinylidene fluoride) (PVDF) and poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) are prepared by direct-ink-writing (DIW) by varying solvent evaporation temperature and fill density percentage. Different morphologies for both polymers are obtained, including dense films and porous membranes, as well as different electroactive β-phase content, thermal and mechanical properties. The dielectric constant and piezoelectric d₃₃ coefficient for dense films reaches up to 16 at 1 kHz and 4 pC N⁻¹, respectively for PVDF-HFP with a fill density of 80 and a solvent evaporation temperature of 50 °C. Porous structures are developed for battery separator membranes in lithium-ion batteries, with a highest ionic conductivity value of 3.8 mS cm⁻¹ for the PVDF-HFP sample prepared with a fill density of 100 and a solvent evaporation temperature of 25 °C, the sample showing an excellent cycling performance. It is demonstrated that electroactive films and membranes can be prepared by direct-ink writing suitable for sensors/actuators and energy storage systems.     

A Methionine Chemical Shift Based Order Parameter Characterizing Global Protein Dynamics

Coupling of side chain dynamics over long distances is an important component of allostery. Methionine side chains show the largest intrinsic flexibility among methyl-containing residues but the actual degree of conformational averaging depends on the proximity and mobility of neighboring residues. The ¹³C NMR chemical shifts of the methyl groups of methionine residues located at long distances in the same protein show a similar scaling with respect to the values predicted from the static X-ray structure by quantum methods. This results in a good linear correlation between calculated and observed chemical shifts. The slope is protein dependent and ranges from zero for the highly flexible calmodulin to 0.7 for the much more rigid calcineurin catalytic domain. The linear correlation is indicative of a similar level of side-chain conformational averaging over long distances, and the slope of the correlation line can be interpreted as an order parameter of the global side-chain flexibility.     

Cu/SBA-15 as adsorbent for propane/propylene separation

Samples of mesoporous silica SBA-15 were prepared under hydrothermal conditions where Cu cations were incorporated to the structure by impregnation in order to compare the adsorption behavior in the presence and absence of this element. The adsorption/desorption equilibrium isotherms of propylene, propane, and N₂ were measured to evaluate their usefulness in the propane/propylene separation. All the adsorption isotherms of SBA-15 measured in the absence of Cu cations were described by the Freundlich equation, while the adsorption isotherms of propane on Cu/SBA-15 were better represented by the Henry equation and those of propylene were satisfactorily described by the Langmuir model in the range P < 100 Torr. The adsorption uptake of propylene increased and that of propane decreased in Cu/SBA-15 as compared to the amounts observed in the SBA-15 sample. The presence of Cu atoms in the adsorbent lattice increased the selectivity towards propylene. Under some working conditions the adsorbed amount of propylene in Cu/SBA-15 sample was totally reversible and the propane uptake, negligible.     

In vivo aging of gutta‐percha dental cone

Gutta‐percha cone is the most widely used material for root canal filling. The in vivo aging of this cone focus on the degradation of its main organic component, trans‐1,4‐polyisoprene, was studied. Aged cones (25 samples) from 2 to 30 years of root canal filling were extracted from different patients in the occasion of retreatment by mechanical way. The information about the aging time was given by the patients. Gel‐permeation chromatography (GPC) and infrared spectroscopy (FTIR) were the analytical techniques used. Polyisoprene degrades with time of aging, but in a slow process. Decrease in polymer molar mass from 5.7 × 10⁵ to 1.7 × 10⁵ g/mol was observed in polyisoprene from cone after 30 years of root canal filling and inside a noninfected tooth. In tooth with caries and periodontal infection, the decrease in molar mass is higher (4.6 × 10⁴ g/mol in cone with 10 years of aging). The production of carbonyl and hydroxyl groups in the aged material indicates that the process is oxidative, even in closed teeth. In these cases, the oxygen could be provided from tissue fluid. The degradation mechanism is complex and depends on many factors, besides time of root canal filling. The dental problem caused by the aging could be the production and migration of cytotoxic substances to periodontal ligament and the reduction on the canal sealing property due to the polymer weight loss. Both of them could contribute to the root canal treatment failure. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100:4082–4088, 2006     

Semi-interpenetrating polymer networds produced with polyethylene terephthalate oligomer and unsaturated polyester resin

A series of semi-interpenetrating polymer networks (semi-IPN's) based on different compositions of an acyclic polyethylene terephthalate oligomer and unsaturated polyester resin (UP) were prepared. The oligomer was dissolved in the resin containing styrene crosslinker. Later this mixture was crosslinked at room temperature using methyl ethyl ketone peroxide catalyst and cobalt naphtanate as promoter. The tensile strength of the IPN's decreases as the concentration of oligomer increases, whereas, elongation to break increases. A characterization of the oligomer used is also presented.     

Asymptotic solvers for second-order differential equation systems with multiple frequencies

In this paper, an asymptotic expansion is constructed to solve second-order differential equation systems with highly oscillatory forcing terms involving multiple frequencies. An asymptotic expansion is derived in inverse of powers of the oscillatory parameter and its truncation results in a very effective method of dicretizing the differential equation system in question. Numerical experiments illustrate the effectiveness of the asymptotic method in contrast to the standard Runge–Kutta method.     

A 2D algorithm with asymmetric workload for the UPC conjugate gradient method

This paper examines four different strategies, each one with its own data distribution, for implementing the parallel conjugate gradient (CG) method and how they impact communication and overall performance. Firstly, typical 1D and 2D distributions of the matrix involved in CG computations are considered. Then, a new 2D version of the CG method with asymmetric workload, based on leaving some threads idle during part of the computation to reduce communication, is proposed. The four strategies are independent of sparse storage schemes and are implemented using Unified Parallel C (UPC), a Partitioned Global Address Space (PGAS) language. The strategies are evaluated on two different platforms through a set of matrices that exhibit distinct sparse patterns, demonstrating that our asymmetric proposal outperforms the others except for one matrix on one platform.