Percolation in binary mixtures of linkers and particles: Chaining vs branching.

Equilibrium gels of colloidal particles can be realized through the introduction of a second species, a linker that mediates the bonds between colloids. A gel forming binary mixture whose linkers can self-assemble into linear chains while still promoting the aggregation of particles is considered in this work. The particles are patchy particles with fC patches of type C and the linkers are patchy particles with 2 patches of type A and fB patches of type B. The bonds between patches of type A (AA bonds) promote the formation of linear chains of linkers. Two different ways (model A and model B) of bonding the linkers to the particles-or inducing branching-are studied. In model A, there is a competition between chaining and branching, since the bonding between linkers and particles takes place through AC bonds only. In model B, the linkers aggregate to particles through bonds BC only, making chaining and branching independent. The percolation behavior of these two models is studied in detail, employing a generalized Flory-Stockmayer theory and Monte Carlo simulations. The self-assembly of linkers into chains reduces the fraction of particles needed for percolation to occur (models A and B) and induces percolation when the fraction of particles is high (model B). Percolation by heating and percolation loops in temperature-composition diagrams are obtained when the formation of chains is energetically favorable by increasing the entropic gain of branching (model A). Chaining and branching are found to follow a model dependent relation at percolation, which shows that, for the same composition, longer chains require less branching for percolation to occur.

Building up DNA, bit by bit: a simple description of chain assembly.

We simulate the assembly of DNA copolymers from two types of short duplexes (short double strands with a single-stranded overhang at each end), as described by the oxDNA model. We find that the statistics of chain lengths can be well reproduced by a simple theory that treats the association of particles into ideal (i.e., non-interacting) clusters as a reversible chemical reaction. The reaction constants can be predicted either from SantaLucia's theory or from Wertheim's thermodynamic perturbation theory of association for spherical patchy particles. Our results suggest that theories incorporating very limited molecular detail may be useful for predicting the broad equilibrium features of copolymerisation.

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.

Remnants of the disappearing critical point(s) in patchy fluids with distinct interaction patches.

We investigate the disappearance of the critical points of a model consisting of particles decorated with two patches of type A and a variable number (n) of patches of type B (2AnB patchy particles), in which only AA and AB bonds can form. This has been shown to exhibit a very rich phase behavior including one, two, or no liquid-vapor critical points, depending on two parameters: the ratio of the volumes available to each type of bond and the ratio of the bond strengths. We apply Wertheim's theory in the limit of strong AA bonds to a lattice version of the model [Almarza et al., J. Chem. Phys. 137, 244902 (2012)] and show that the critical point does not always vanish at zero density and temperature, in contrast with results for particles decorated with only one type of patch. We uncover two remnants of the critical points-the lines of maximum and ideal compressibility-that survive even when no critical points are present.

The effect of CO2 9.3 µm short-pulsed laser irradiation in enamel erosion reduction with and without fluoride applications-a randomized, controlled in vitro study.

The aim of this in vitro study was to evaluate the protective effect of short-pulsed CO2 9.3 µm laser irradiation against erosion in human enamel without and combined with TiF4 and AmF/NaF/SnCl2 applications, respectively, as well as compared to the protective effect of these fluoride treatments alone. After polishing, ninety enamel samples (3 × 3mm) were used for 9 different treatment groups: 4% TiF4 gel (pH 1.5, 24,533 ppm F-); AmF/NaF/SnCl2 rinse (pH 4.5; 500 ppm F-, 800 ppm Sn2); CO2 laser (average power 0.58 W); CO2 laser (0.58 W) + TiF4; CO2 laser (0.58 W) + AmF/NaF/SnCl2; CO2 laser (0.69 W); CO2 laser (0.69 W) + TiF4; CO2 laser (0.69 W) + AmF/NaF/SnCl2; negative control (deionized water). TiF4 gel was brushed on only once before the first erosive cycling, while samples treated with AmF/NaF/SnCl2 were daily immersed in 5 ml of the solution before cycling. Laser treatment occurred with a CO2 laser (wavelength 9.3 µm, pulse repetition rate 100 Hz, pulse duration 14.6 µs/18 µs, average power 0.58 W/0.69 W, fluence 1.9 J/cm2/2.2 J/cm2, beam diameter 0.63 mm, irradiation time 10 s, air cooling). TiF4 was applied only once, while AmF/NaF/SnCl2 was applied once daily before the erosive challenge. Surface loss (in µm) was measured with optical profilometry immediately after treatment, and after 5 and 10 days of erosive cycling (0.5% citric acid, pH 2.3, 6 × 2 min/day). Additionally, scanning electron microscopy investigations were performed. All application measures resulted in loss of surface height immediately after treatment. After 5 days, significantly reduced surface loss was observed after applying laser irradiation (both power settings) followed by applications of TiF4 or AmF/NaF/SnCl2 solution (p < 0.05; 2-way ANOVA and Tukey test) compared to fluoride application alone. After 10 days, compared to after 5 days, a reduced tissue loss was observed in all groups treated with AmF/NaF/SnCl2 solution. This tissue gain occurred with the AmF/NaF/SnCl2 application alone and was significantly higher when the application was combined with the laser use (p < 0.05). Short-pulsed CO2 9.3 µm laser irradiation followed by additional application of AmF/NaF/SnCl2 solution significantly reduces the progression of dental enamel erosion in vitro.

Variations in maternal adenylate cyclase genes are associated with congenital Zika syndrome in a cohort from Northeast, Brazil.

BACKGROUND: Vertical transmission of Zika virus (ZIKV) is associated with congenital malformations but the mechanism of pathogenesis remains unclear. Although host genetics appear to play a role, no genetic association study has yet been performed to evaluate this question. In order to investigate if maternal genetic variation is associated with Congenital Zika Syndrome (CZS), we conducted a case-control study in a cohort of Brazilian women infected with ZIKV during pregnancy. METHODS: A total of 100 women who reported symptoms of zika during pregnancy were enrolled and tested for ZIKV. Among 52 women positive for ZIKV infection, 28 were classified as cases and 24 as controls based on the presence or absence of CZS in their infants. Variations in the coding region of 205 candidate genes involved in cAMP signaling or immune response were assessed by high throughput sequencing and tested for association with development of CZS. RESULTS: From the 817 single nucleotide variations (SNVs) included in association analyses, 22 SNVs in 17 genes were associated with CZS under an additive model (alpha = 0.05). Variations c.319T>C (rs11676272) and c.1297G>A, located at ADCY3 and ADCY7 genes showed the most prominent effect. The association of ADCY3 and ADCY7 genes was confirmed using a Sequence Kernel Association Test to assess the joint effect of common and rare variations, and results were statistically significant after adjustment for multiple comparisons (P < 0.002). CONCLUSION: These results suggest that maternal ADCY genes contribute to ZIKV pathogenicity and influence the outcome of CZS, being promising candidates for further replication studies and functional analysis.

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.

Effects of high-impact exercise on the physical properties of bones of ovariectomized rats fed to a high-protein diet.

The aim of this study was to evaluate the effects of high-impact physical exercise as a prophylactic and therapeutic means in osteopenic bones of rats submitted to ovariectomy and protein diet intake. A total of 64 Wistar rats were divided into eight groups (n = 8 each), being: OVX, ovx, standard diet and sedentary; OVXE, ovx, standard diet and jump; OVXP, ovx, high-protein diet and sedentary; and OVXEP, ovx, high-protein diet and jump; SH, sham, standard diet and sedentary; SHE, sham, standard diet and jump; SHP, sham, high-protein diet and sedentary; and SHEP, sham, high-protein diet and jump. OVX surgery consists of ovariectomy, and sham was the control surgery. The jumping protocol consisted of 20 jumps/day, 5 days/week. The bone structure was evaluated by densitometry, mechanical tests, histomorphometric, and immunohistochemical analyses. A high-protein diet resulted in increased bone mineral density (P = .049), but decreased maximal load (P = .026) and bone volume fraction (P = .023). The benefits of physical exercise were demonstrated by higher values of the maximal load in the trained groups compared to the sedentary groups (P < .001). The sham groups had decreased immunostaining of osteocalcin (P = .004) and osteopontin (P = .010) compared to ovx groups. However, the high-protein diet (P = .005) and jump exercise (P = .017) resulted in lower immunostaining of osteopontin compared to the standard diet and sedentary groups, respectively. In this experimental model, it was concluded that ovariectomy and a high-fat diet can negatively affect bone tissue and the high-impact exercise was not enough to suppress the deleterious effects caused by the protein diet and ovariectomy.

Modeling adult emergence and fecundity of factitious hosts under different food sources supports massive egg production management.

Ephestia kuehniella (Lepidoptera, Pyralidae) and Sitotroga cerealella (Lepidoptera, Gelechiidae) are important factitious hosts used for production of biological control agents. Their differences in terms of biology and behavior require adjustments in their mass production, particularly when using corn or barley as food in grain or in bran. We modeled adult emergence, oviposition period and egg production along time after emergence, as a function of the food source. Significant differences between hosts or food type were found for these variables and for adult weight but not for sex ratio. Our results confirm the possibility of mass production of these hosts using corn or barley as food source. Integrating adult emergence patterns and age specific fecundity patterns into a single model, it is clear that rearing E. kuehniella on barley would result in the highest egg output in much shorter time than E. kuehniella on corn or S. cerealella on barley.

Generalization of Wertheim's theory for the assembly of various types of rings.

We generalize Wertheim's first order perturbation theory to account for the effect in the thermodynamics of the self-assembly of rings characterized by two energy scales. The theory is applied to a lattice model of patchy particles and tested against Monte Carlo simulations on a fcc lattice. These particles have 2 patches of type A and 10 patches of type B, which may form bonds AA or AB that decrease the energy by εAA and by εAB ≡ rεAA, respectively. The angle θ between the 2 A-patches on each particle is fixed at 60°, 90° or 120°. For values of r below 1/2 and above a threshold rth(θ) the models exhibit a phase diagram with two critical points. Both theory and simulation predict that rth increases when θ decreases. We show that the mechanism that prevents phase separation for models with decreasing values of θ is related to the formation of loops containing AB bonds. Moreover, we show that by including the free energy of B-rings (loops containing one AB bond), the theory describes the trends observed in the simulation results, but that for the lowest values of θ, the theoretical description deteriorates due to the increasing number of loops containing more than one AB bond.

Three-dimensional patchy lattice model: ring formation and phase separation.

We investigate the structural and thermodynamic properties of a model of particles with 2 patches of type A and 10 patches of type B. Particles are placed on the sites of a face centered cubic lattice with the patches oriented along the nearest neighbor directions. The competition between the self-assembly of chains, rings, and networks on the phase diagram is investigated by carrying out a systematic investigation of this class of models, using an extension of Wertheim's theory for associating fluids and Monte Carlo numerical simulations. We varied the ratio r ≡ εAB/εAA of the interaction between patches A and B, εAB, and between A patches, εAA (εBB is set to 0) as well as the relative position of the A patches, i.e., the angle θ between the (lattice) directions of the A patches. We found that both r and θ (60°, 90°, or 120°) have a profound effect on the phase diagram. In the empty fluid regime (r < 1/2) the phase diagram is reentrant with a closed miscibility loop. The region around the lower critical point exhibits unusual structural and thermodynamic behavior determined by the presence of relatively short rings. The agreement between the results of theory and simulation is excellent for θ = 120° but deteriorates as θ decreases, revealing the need for new theoretical approaches to describe the structure and thermodynamics of systems dominated by small rings.

Straight core structure of DNA replication origins in the mammalian AMPD2 locus.

Identification of the nucleotide consensus sequence in mammalian replication origins is a difficult and controversial problem. The hypothesis that local DNA topology could be involved in recognition by replication proteins is an exciting possibility. Secondary DNA structures, including intrinsically bent DNA, can be easily detected, and they may indicate a specific pattern in or near mammalian replication origins. This work presents the entire mapping of the intrinsically bent DNA sites (IBDSs), using in silico analysis and a circular permutation assay, of the DNA replication origins oriGNAI3, oriC, oriB, and oriA in the mammalian amplified AMPD2 gene domain. The results show that each origin presents an IBDS that flanks the straight core of these DNA replication sites. In addition, the in silico prediction of the nucleosome positioning reveals a strong indication that the center of an IBDS is localized in a nucleosome-free region (NFR). The structure of each of these curved sites is presented together with their helical parameters and topology. Together, the data that we present here indicate that the oriGNAI3 origin where preferential firing to the replication initiation events in the amplified AMPD2 domain occurs is the only origin that presents a straight, narrow region that is flanked on both sides by two intrinsically bent DNA sites within a short distance (~300 bp); however, all of the origins present at least one IBDS, which is localized in the NFR region. These results indicate that structural features could be implicated in the mammalian DNA replication origin and support the possibility of detecting and characterizing these segments.

The phased Solanum okadae genome and Petota pangenome analysis of 23 other potato wild relatives and hybrids.

Potato is an important crop in the genus Solanum section Petota. Potatoes are susceptible to multiple abiotic and biotic stresses and have undergone constant improvement through breeding programs worldwide. Introgression of wild relatives from section Petota with potato is used as a strategy to enhance the diversity of potato germplasm. The current dataset contributes a phased genome assembly for diploid S. okadae, and short read sequences and de novo assemblies for the genomes of 16 additional wild diploid species in section Petota that were noted for stress resistance and were of interest to potato breeders. Genome sequence data for three additional genomes representing polyploid hybrids with cultivated potato, and an additional genome from non-tuberizing S. etuberosum, which is outside of section Petota, were also included. High quality short reads assemblies were achieved with genome sizes ranging from 575 to 795 Mbp and annotations were performed utilizing transcriptome sequence data. Genomes were compared for presence/absence of genes and phylogenetic analyses were carried out using plastome and nuclear sequences.

Antifungal activity of Annona crassiflora Mart. dichloromethane fraction against strains of C. albicans.

Products derived from medicinal plants with antimicrobial activity are considered a promising alternative in the treatment of fungal infections. In this perspective, this study proposed to evaluate the antifungal activity of the dichloromethane fraction of Annona crassiflora Mart. against C. albicans strains. Tests were carried out to determine Minimum Inhibitory Concentration (MIC), Minimum Fungicide Concentration (MFC), microbial growth kinetics, fungal cell wall and membrane mechanisms of action, antifungal biofilm activity, and cytotoxic effects on human erythrocytes. The extract presented MIC and MFC values that ranged from 256 µg/mL to 1,024 µg/mL, with fungicidal activity in the microbial growth kinetics assay. The mechanism of action did not occur through damage to the cell wall or via binding to ergosterol in the membrane, though the fraction presents activity against biofilm and is not cytotoxic in human erythrocytes. The dichloromethane fraction of Annona crassiflora Mart. presented antifungal activity and reduced biofilm growth, without toxicity against human erythrocytes; however, further studies are needed to define its mechanism of action.

Dental injury after conventional direct laryngoscopy: a prospective observational study.

This observational study assessed the frequency and risk factors of dental damage after classic direct laryngoscopy for tracheal intubation in 536 adult patients. The patients' sex, age, height, weight, dental condition, dental mobility, Mallampati class, interincisor gap, thyromental distance, neck circumference, and head and neck extension were recorded. From anaesthesia records, the difficulty of intubation, the number of attempts, type of neuromuscular blocking agent used and duration of anaesthesia were recorded. After anaesthesia, examination revealed that 134 patients (25.0%) had dental damage affecting 162 teeth (147 maxillary; 15 mandibular). Enamel fracture was the commonest injury. In tooth number 21, the interincisor gap (OR 2.5 (95% CI 1.0-5.9)) and in tooth number 22, the number of intubation attempts (OR 5.3 (95% CI 1.3-22.0)) were considered a risk factor for dental injury. Conventional direct laryngoscopy is associated with a strikingly high incidence of dental damage, although specific risk factors remain unclear.

COVID-19 immunotherapy: a mathematical model.

The pandemic caused by SARS-CoV-2 is responsible for a terrible health devastation with profoundly harmful consequences for the economic, social and political activities of communities on a global scale. Extraordinary efforts have been made by the world scientific community, who, in solidarity, shared knowledge so that effective vaccines could be produced quickly. However, it is still important to study therapies that can reduce the risk, until group immunity is reached, which, globally, will take a time that is still difficult to predict. On the other hand, the immunity time guaranteed by already approved vaccines is still uncertain. The current study proposes a therapy whose foundation lies in the important role that innate immunity may have, by preventing the disease from progressing to the acute phase that may eventually lead to the patient's death. Our focus is on natural killer (NK) cells and their relevant role. NKs are considered the primary defence lymphocytes against virus-infected cells. They play a critical role in modulating the immune system. Preliminary studies in COVID-19 patients with severe disease suggest a reduction in the number and function of NK cells, resulting in decreased clearance of infected and activated cells and unchecked elevation of inflammation markers that damage tissue. SARS-CoV-2 infection distorts the immune response towards a highly inflammatory phenotype. Restoring the effector functions of NK cells has the potential to correct the delicate immune balance needed to effectively overcome SARS-CoV-2 infection.

Characterization of Leishmania infantum thiol-dependent reductase 1 and evaluation of its potential to induce immune protection.

The need to develop an effective vaccine against leishmaniasis to prevent the 2 million new cases each year led to the search for antigens able to elicit protection against infection with Leishmania. In this study, we have characterized a parasite-specific protein of Leishmania infantum named thiol-dependent reductase 1 (TDR1). The protein is present in both life cycle stages of L. infantum with a notable higher expression in the amastigote forms, suggesting a role in the interaction between the parasite and the mammalian host. Thiol-dependent reductase 1 is localized in the cytosol, although we were able to detect the protein in the culture medium of both promastigotes and axenic amastigotes, and consequently, TDR1 is considered an excreted/secreted molecule of the parasite. Therefore, we have evaluated the potential of TDR1 recombinant protein to protect against experimental challenge with L. infantum parasites using a murine model. Despite a reduction in spleen parasite load in the chronic phase of disease, TDR1 administration was not effective in the protection of Balb/c mice against visceral leishmaniasis and thus TDR1 do not have a crucial role in the modulation of mammalian host immune response, as observed with its protein counterpart Tc52 of Trypanosoma cruzi.

The nature of the ordered phase of the confined self-assembled rigid rod model.

We investigate the nature of the ordered phase and the orientational correlations between adjacent layers of the confined three-dimensional self-assembled rigid rod model, on the cubic lattice. We find that the ordered phase at finite temperatures becomes uniaxial in the thermodynamic limit, by contrast to the ground state (partial) order where the orientation of the uncorrelated layers is perpendicular to one of the three lattice directions. The increase of the orientational correlation between layers as the number of layers increases suggests that the unconfined model may also exhibit uniaxial ordering at finite temperatures.

Three-dimensional patchy lattice model for empty fluids.

The phase diagram of a simple model with two patches of type A and ten patches of type B (2A10B) on the face centred cubic lattice has been calculated by simulations and theory. Assuming that there is no interaction between the B patches the behavior of the system can be described in terms of the ratio of the AB and AA interactions, r. Our results show that, similarly to what happens for related off-lattice and two-dimensional lattice models, the liquid-vapor phase equilibria exhibit reentrant behavior for some values of the interaction parameters. However, for the model studied here the liquid-vapor phase equilibria occur for values of r lower than 1/3, a threshold value which was previously thought to be universal for 2AnB models. In addition, the theory predicts that below r=1/3 (and above a new condensation threshold which is <1/3) the reentrant liquid-vapor equilibria are so extreme that it exhibits a closed loop with a lower critical point, a very unusual behavior in single-component systems. An order-disorder transition is also observed at higher densities than the liquid-vapor equilibria, which shows that the liquid-vapor reentrancy occurs in an equilibrium region of the phase diagram. These findings may have implications in the understanding of the condensation of dipolar hard spheres given the analogy between that system and the 2AnB models considered here.