Sustained PGC-1α2 or PGC-1α3 expression induces astrocyte dysfunction and degeneration.

Peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) transcriptional coactivators are key regulators of energy metabolism-related genes and are expressed in energy-demanding tissues. There are several PGC-1α variants with different biological functions in different tissues. The brain is one of the tissues where the role of PGC-1α isoforms remains less explored. Here, we used a toxin-based mouse model of Parkinson's disease (PD) and observed that the expression levels of variants PGC-1α2 and PGC-1α3 in the nigrostriatal pathway increases at the onset of dopaminergic cell degeneration. This increase occurs concomitant with an increase in glial fibrillary acidic protein levels. Since PGC-1α coactivators regulate cellular adaptive responses, we hypothesized that they could be involved in the modulation of astrogliosis induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Therefore, we analysed the transcriptome of astrocytes transduced with expression vectors encoding PGC-1α1 to 1α4 by massively parallel sequencing (RNA-seq) and identified the main cellular pathways controlled by these isoforms. Interestingly, in reactive astrocytes the inflammatory and antioxidant responses, adhesion, migration, and viability were altered by PGC-1α2 and PGC-1α3, showing that sustained expression of these isoforms induces astrocyte dysfunction and degeneration. This work highlights PGC-1α isoforms as modulators of astrocyte reactivity and as potential therapeutic targets for the treatment of PD and other neurodegenerative disorders.

Effect of discharge opioid on persistent postoperative opioid use: a retrospective cohort study comparing tapentadol with oxycodone.

Opioid harm can vary by opioid type. This observational study examined the effect of opioid type (oxycodone vs. tapentadol) on rates of persistent postoperative opioid use ('persistence'). We linked hospital and community pharmacy data for surgical patients who were dispensed discharge opioids between 1 January 2016 and 30 September 2021. Patients were grouped by opioid experience ('opioid-naive' having received no opioids in the 3 months before discharge) and formulation of discharge opioid (immediate release only or modified release ± immediate release). Mixed-effects logistic regression models predicted persistence (continued use of any opioid at 90 days after discharge), controlling for key persistence risk factors. Of the 122,836 patients, 2.31% opioid-naive and 27.24% opioid-experienced patients met the criteria for persistence. For opioid-naive patients receiving immediate release opioids, there was no significant effect of opioid type. Tapentadol modified release was associated with significantly lower odds of persistence compared with oxycodone modified release, OR (95%CI) 0.81 (0.69-0.94) for opioid-naive patients and 0.81 (0.71-0.93) for opioid-experienced patients. Among patients who underwent orthopaedic surgery (n = 19,832), regardless of opioid experience or opioid formulation, the odds of persistence were significantly lower for those who received tapentadol compared with oxycodone. This was one of the largest and most extensive studies of persistent postoperative opioid use, and the first that specifically examined persistence with tapentadol. There appeared to be lower odds of persistence for tapentadol compared with oxycodone among key subgroups, including patients prescribed modified release opioids and those undergoing orthopaedic surgery.

Wetting of a solid surface by active matter.

A lattice model is used to study repulsive active particles at a planar surface. A rejection-free Kinetic Monte Carlo method is employed to characterize the wetting behaviour. The model predicts a motility-induced phase separation of active particles, and the bulk coexistence of dense liquid-like and dilute vapour-like steady states is determined. An "ensemble", with a varying number of particles, analogous to a grand canonical ensemble in equilibrium, is introduced. The formation and growth of the liquid film between the solid surface and the vapour phase is investigated. At constant activity, as the system is brought towards coexistence from the vapour side, the thickness of the adsorbed film exhibits a divergent behaviour regardless of the activity. This suggests a complete wetting scenario along the full coexistence curve.

Modeling of Cell-Mediated Self-Assembled Colloidal Scaffolds.

A critical step in tissue engineering is the design and synthesis of 3D biocompatible matrices (scaffolds) to support and guide the proliferation of cells and tissue growth. The most existing techniques rely on the processing of scaffolds under controlled conditions and then implanting them in vivo, with questions related to biocompatibility and implantation that are still challenging. As an alternative, it was proposed to assemble the scaffolds in loco through the self-organization of colloidal particles mediated by cells. To overcome the difficulty to test experimentally all the relevant parameters, we propose the use of large-scale numerical simulation as a tool to reach useful predictive information and to interpret experimental results. Thus, in this study, we combine experiments, particle-based simulations, and mean-field calculations to show that, in general, the size of the self-assembled scaffold scales with the cell-to-particle ratio. However, we have found an optimal value of this ratio, for which the size of the scaffold is maximal when the cell-cell adhesion is suppressed. These results suggest that the size and structure of the self-assembled scaffolds may be designed by tuning the adhesion between cells in the colloidal suspension.

Smoluchowski equations for linker-mediated irreversible aggregation.

We developed a generalized Smoluchowski framework to study linker-mediated aggregation, where linkers and particles are explicitly taken into account. We assume that the bonds between linkers and particles are irreversible, and that clustering occurs through limited diffusion aggregation. The kernel is chosen by analogy with single-component diffusive aggregation but the clusters are distinguished by their number of particles and linkers. We found that the dynamics depends on three relevant factors, all tunable experimentally: (i) the ratio of the diffusion coefficients of particles and linkers; (ii) the relative number of particles and linkers; and (iii) the maximum number of linkers that may bond to a single particle. To solve the Smoluchoski equations analytically we employ a scaling hypothesis that renders the fraction of bondable sites of a cluster independent of the size of the cluster, at each instant. We perform numerical simulations of the corresponding lattice model to test this hypothesis. We obtain results for the asymptotic limit, and the time evolution of the bonding probabilities and the size distribution of the clusters. These findings are in agreement with experimental results reported in the literature and shed light on unexplained experimental observations.

Development of dextrin-amphotericin B formulations for the treatment of Leishmaniasis.

The most effective medicines available for the treatment of leishmaniasis, a life-threatening disease, exhibit serious toxicological issues. To achieve better therapeutic efficiency while decreasing toxicity associated with amphotericin B (AmB), water-soluble dextrin-AmB (Dex-AmB) formulations were developed. Self-assembled nanocomplexes were formed by dissolving Dex and AmB in alkaline borate buffer, followed by dialysis and either freeze-drying (FD) or nano spray-drying (SD), yielding water dispersible particles with a diameter of 214 nm and 347 nm, respectively. The very simple production process allowed the formation of amorphous inclusion complexes containing 14% of AmB in the form of monomers and water-soluble aggregates. Nanocomplexes were effective against parasites in axenic culture (IC50 of 0.056 and 0.096 µM for L. amazonensis and 0.030 and 0.044 µM for L. infantum, respectively for Dex-AmB FD and Dex-AmB SD) and in decreasing the intramacrophagic infection with L. infantum (IC50 of 0.017 and 0.023 µM, respectively for Dex-AmB FD and Dex-AmB SD). Also, the formulations were able to significantly reduce the cytotoxicity of AmB. Overall, this study demonstrates the suitability of dextrin as an AmB carrier and the facile and inexpensive development of a delivery system for the treatment of leishmaniasis.

A dry and fully dispersible bacterial cellulose formulation as a stabilizer for oil-in-water emulsions.

Bacterial cellulose (BC) is an emerging alternative to plant cellulose in different applications. Several works demonstrated the potential of never-dried BC; however, envisioning real industrial applications, a dry product retaining its functional properties upon rehydration is preferable. A dry and completely redispersible formulation of BC with carboxymethyl cellulose (CMC) was prepared by Spray-drying. The obtained material showed a Zeta Potential of (-67.0 ±â€¯3.9) mV, a Dv(50) of (601 ±â€¯19.7) µm and was able to decrease the oil/water interface energy. The dry BC:CMC formulation was employed as a stabilizer in oil-in-water emulsions, in parallel with commercial plant celluloses and Xanthan gum. The emulsions were monitored over time by optical microscopy and characterized by rheological measurements. BC:CMC effectively stabilized emulsions against coalescence and creaming, at a concentration of 0.50 % - contrarily to other commercial dry celluloses - due to the Pickering effect and to the structuring of the continuous phase, as seen with Cryo-SEM.

Perfil de ácidos graxos do leite de vacas Holandês x Gir alimentadas com silagem de milho e concentrado contendo ou não glicerina bruta / Milk fatty acid profile from Holstein x Gyr cows fed corn silage and concentrate containing or not crude glycerin

O objetivo deste estudo foi avaliar o perfil de ácidos graxos (AG) do leite de vacas alimentadas com dietas à base de silagem de milho contendo 0% e 8,9% de glicerina bruta (GB) na matéria seca (MS). Foram utilizadas 18 vacas Holandês x Gir com 48±18 dias em lactação, produzindo 19,8±4,9kg/dia de leite. Utilizou-se delineamento de blocos ao acaso, com nove vacas/tratamento e duas medidas repetidas no tempo, com os resultados analisados por modelos mistos. A inclusão de GB na dieta não alterou a ingestão de MS, mas reduziu os consumos dos AG oleico, linoleico e α-linolênico. Os teores dos AG mirístico, palmítico, rumênico, vacênico, esteárico, oleico, linoleico, α-linolênico e CLA trans-10 cis-12 na gordura do leite foram semelhantes entre dietas. A inclusão de GB reduziu os teores dos AG elaídico e C18:1 trans-10 e aumentou os teores dos AG de cadeia ímpar linear e do ácido láurico. Não houve efeito da inclusão da GB sobre os índices de aterogenicidade e trombogenicidade da gordura do leite. Concluiu-se que a inclusão de glicerina bruta em dieta à base de silagem de milho não afetou a qualidade nutricional da gordura do leite de vacas Holandês x Gir.(AU)

The objective of this study was to evaluate the milk fatty acid (FA) composition of cows fed corn silage-based diets containing 0% and 8.9% of crude glycerin (GB) on a dry matter (DM) basis. Eighteen Holstein x Gyr cows with 48±18 days in milk and producing 19.8±4.9kg milk/day were used in the study. The experimental design was a randomized block with nine cows per treatment and two repeated measures. Results were analyzed using mixed models. The milk fat contents of myristic, palmitic, rumenic, vaccenic, estearic, oleic, linoleic, α-linolenic, and trans-10 cis-12 CLA were similar between diets. Dietary inclusion of GB decreased elaidic and trans-10 C18:1, and increased lauric acid and odd linear-chain FA contents in milk fat. Both atherogenicity and trombogenicity indices were unaffected by GB inclusion. It was concluded that GB inclusion in corn silage-based diets had no effect on the nutritional quality of milk fat from Holstein x Gyr dairy cows.(AU)

Optimal number of linkers per monomer in linker-mediated aggregation.

We study the dynamics of diffusion-limited irreversible aggregation of monomers, where bonds are mediated by linkers. We combine kinetic Monte Carlo simulations of a lattice model with a mean-field theory to study the dynamics when the diffusion of aggregates is negligible and only monomers diffuse. We find two values of the number of linkers per monomer which maximize the size of the largest aggregate. We explain the existence of the two maxima based on the distribution of linkers per monomer. This observation is well described by a simple mean-field model. We also show that a relevant parameter is the ratio of the diffusion coefficients of monomers and linkers. In particular, when this ratio is close to ten, the two maxima merge at a single maximum.

Crossover from three- to six-fold symmetry of colloidal aggregates in circular traps.

At sufficiently low temperatures and high densities, repulsive spherical particles in two-dimensions (2d) form close-packed structures with six-fold symmetry. By contrast, when the interparticle interaction has an attractive anisotropic component, the structure may exhibit the symmetry of the interaction. We consider a suspension of spherical particles interacting through an isotropic repulsive potential and a three-fold symmetric attractive interaction, confined in circular potential traps in 2d. We find that, due to the competition between the interparticle and the external potentials, the particles self-organize into structures with three- or six-fold symmetry, depending on the width of the traps. For intermediate trap widths, a core-shell structure is formed, where the core has six-fold symmetry and the shell is three-fold symmetric. When the width of the trap changes periodically in time, the symmetry of the colloidal structure also changes, but it does not necessarily follow that of the corresponding static trap.

Dynamics of a network fluid within the liquid-gas coexistence region.

Low-density networks of molecules or colloids are formed at low temperatures when the interparticle interactions are valence limited. Prototypical examples are networks of patchy particles, where the limited valence results from highly directional pairwise interactions. We combine extensive Langevin simulations and Wertheim's theory of association to study these networks. We find a scale-free (relaxation) dynamics within the liquid-gas coexistence region, which differs from that usually observed for isotropic particles. While for isotropic particles the relaxation dynamics is driven by surface tension (coarsening), when the valence is limited, the slow relaxation proceeds through the formation of an intermediate non-equilibrium gel via a geometrical percolation transition in the Random Percolation universality class. We show that the slow dynamics is universal, being also observed outside the coexistence region at low temperatures in the single phase region.

Interaction anisotropy and the KPZ to KPZQ transition in particle deposition at the edges of drying drops.

The deposition process at the edge of evaporating colloidal drops varies with the shape of suspended particles. Experiments with prolate ellipsoidal particles suggest that the spatiotemporal properties of the deposit depend strongly on particle aspect ratio. As the aspect ratio increases, the particles form less densely-packed deposits and the statistical behavior of the deposit interface crosses over from the Kardar-Parisi-Zhang (KPZ) universality class to another universality class which was suggested to be consistent with the KPZ plus quenched disorder. Here, we numerically study the effect of particle interaction anisotropy on deposit growth. In essence, we model the ellipsoids, at the interface, as disk-like particles with two types of interaction patches that correspond to specific features at the poles and equator of the ellipsoid. The numerical results corroborate experimental observations and further suggest that the deposition transition can stem from interparticle interaction anisotropy. Possible extensions of our model to other systems are also discussed.

Dynamics of Patchy Particles in and out of Equilibrium.

We combine particle-based simulations, mean-field rate equations, and Wertheim's theory to study the dynamics of patchy particles in and out of equilibrium, at different temperatures and densities. We consider an initial random distribution of nonoverlapping three-patch particles, with no bonds, and analyze the time evolution of the breaking and bonding rates of a single bond. We find that the asymptotic (equilibrium) dynamics differs from the initial (out of equilibrium) one. These differences are expected to depend on the initial conditions, temperature, and density.

Dynamics of network fluids.

Network fluids are structured fluids consisting of chains and branches. They are characterized by unusual physical properties, such as, exotic bulk phase diagrams, interfacial roughening and wetting transitions, and equilibrium and nonequilibrium gels. Here, we provide an overview of a selection of their equilibrium and dynamical properties. Recent research efforts towards bridging equilibrium and non-equilibrium studies are discussed, as well as several open questions.

Dynamic Design of Spatial Patterns of Colloidal Suspensions.

We study the collective dynamics of colloidal suspensions in the presence of a time-dependent potential by means of dynamic density functional theory. We consider a nonlinear diffusion equation for the density and show that spatial patterns emerge from a sinusoidal external potential with a time-dependent wavelength. These patterns are characterized by a sinusoidal density with the average wavelength and a Bessel-function envelope with an induced wavelength that depends only on the amplitude of the temporal oscillations. As a generalization of this result, we propose a design strategy to obtain a family of spatial patterns using time-dependent potentials of practically arbitrary shape.

Nematic films at chemically structured surfaces.

We investigate theoretically the morphology of a thin nematic film adsorbed at flat substrate patterned by stripes with alternating aligning properties, normal and tangential respectively. We construct a simple 'exactly-solvable' effective interfacial model where the liquid crystal distortions are accounted for via an effective interface potential. We find that chemically patterned substrates can strongly deform the nematic-air interface. The amplitude of this substrate-induced undulations increases with decreasing average film thickness and with increasing surface pattern pitch. We find a regime where the interfacial deformation may be described in terms of a material-independent universal scaling function. Surprisingly, the predictions of the effective interfacial model agree semi-quantitatively with the results of the numerical solution of a full model based on the Landau-de Gennes theory coupled to a square-gradient phase field free energy functional for a two phase system.

Reliability of the Three-minute All-out Test for Non-motorized Treadmill Tethered Running.

The 3-min all-out test was developed and validated on a cycle ergometer using a modification of a linear mathematical equation (1/time vs. power) obtained from the original critical power model. The purpose of this development was to obtain, in a single test, the aerobic and anaerobic capacity parameters and identify the exercise transition moment from heavy to severe intensity. The aim of this study was to propose an adaptation of the all-out 3-min cycle ergometer to a non-motorized treadmill with tethered running. In addition, we tested the reproducibility of this adapted protocol, highlighting the need for mechanical power evaluation using a specific ergometer. Consequently, 10 physically active individuals visited the laboratory 4 times for testing and data collection. The results suggested that the protocol adaptation for the 3-min all-out test for non-motorized treadmill with tethered running was reproducible and feasible. It was also possible to show that the AO3 application in this ergometer ensures the specificity of the sports that involve the running exercise, from assessment of both aerobic and anaerobic parameters, accomplished in a single day of application.