How does the chain extension of poly (acrylic acid) scale in aqueous solution? A combined study with light scattering and computer simulation

This work adresses the question of the scaling behaviour of polyelectrolytes in solution for a realistic prototype: We show results of a combined experimental (light scattering) and theoretical (computer simulations) investigation of structural properties of poly (acrylic acid) (PAA). Experimentally, we determined the molecular weight (M_W) and the hydrodynamic radius (R_H) by static light scattering for six different PAA samples in aqueous NaCl-containing solution (0.1-1 mol/L) of polydispersity D_P between 1.5 and 1.8. On the computational side, three different variants of a newly developed mesoscopic force field for PAA were employed to determine R_H for monodisperse systems of the same M_W as in the experiments. The force field effectively incorporates atomistic information and one coarse-grained bead corresponds to one PAA monomer. We find that R_H matches with the experimental data for all investigated samples. The effective scaling exponent for R_H is found to be around 0.55, which is well below its asymptotic value for good solvents. Additionally, data for the radius of gyration (R_G) are presented.Comment: 17 pages, 3 figures, submitted to Macromolecule

Colour improvement and stability of white spot lesions following infiltration, micro-abrasion, or fluoride treatments in vitro

SUMMARYBACKGROUND/OBJECTIVES: White spot lesions (WSLs) are unwelcome side effects of fixed appliances that compromise the treatment outcome. Recently, infiltration of WSLs has been introduced as a viable treatment alternative. The objective was to evaluate the colour improvement of WSLs and their stability against discolouration following infiltration, fluoride, or micro-abrasion treatments in vitro. MATERIALS/METHODS: Artificial WSLs were created in bovine enamel (N = 96) using acidic buffer solution (pH 5, 10 days) and were randomly allocated to four groups. Specimens were treated with infiltration (Icon, DMG), fluoride (Elmex Caries Protection, GABA), and micro-abrasion (Opalustre, Ultradent) or remained untreated (control). Groups were discoloured for 24 hours in tea or tea + citric acid. Colour components and visible colour change (L*, a*, b*, ΔE) were measured spectrophotometrically on following time points: baseline, after WSL formation, after treatment, and during discolouration (8, 16, and 24 hours). Data were analysed using Kruskal-Wallis and Mann-Whitney tests. RESULTS: WSL formation increased (L*) in all groups. Only infiltration reduced this effect to baseline. Highest ΔE improvement was obtained by infiltration and micro-abrasion followed by fluoride. This improvement was stable only for infiltration during discolouration. L*, a*, and b* changed significantly during discolouration in all groups except infiltration. Within the same treatment group, discolouration solutions did not differ significantly. LIMITATIONS: In vitro testing cannot replicate the actual mode of colour improvement or stability but can be used for ranking materials and techniques. CONCLUSIONS/IMPLICATIONS: Infiltration and micro-abrasion treatments were capable of diminishing the whitish appearance of WSLs. Only infiltrated WSLs were stable following discolouration challeng

Erosion-inhibiting potential of a stannous chloride-containing fluoride solution under acid flow conditions in vitro

OBJECTIVES: This study aimed to analyse the erosion-inhibiting potential of a single application of stannous chloride-containing fluoride solution on pellicle-covered enamel and dentine under constant acid flow conditions in vitro. DESIGN: Bovine enamel (n=60) and dentine (n=60) samples were exposed 1h to the oral cavity of 4 healthy volunteers to allow for in situ pellicle formation. Pellicle-covered samples were randomly assigned to three groups (each n=20 enamel and n=20 dentine samples; 5 enamel and 5 dentine samples/volunteer) and treated once with a SnCl2/AmF/NaF (800 ppm Sn(II), 500 ppm F, pH 4.5) or a NaF solution (500 ppm F, pH 4.5) for 2 min or remained untreated (controls). Samples were eroded with hydrochloric acid (pH 2.6) in a small erosion chamber at 60 microl/min for 25 min. Calcium release into the acid was monitored in consecutive 30s intervals for 5 min, then at 1 min intervals up to a total erosion time of 25 min using the Arsenazo III procedure. Data were statistically analysed by random-effects linear models (p<0.05). RESULTS: The stannous chloride-containing fluoride solution reduced calcium loss of enamel and dentine to up to 6 min and 3.5 min, respectively. Calcium loss (% of control) amounted from 24+/-7 (30s) up to 93+/-14 (6 min) in enamel and from 38+/-13 (30s) to 87+/-15 (3.5 min) in dentine. The sodium fluoride solution was unable to reduce enamel and dentine erosion at any time point. CONCLUSION: A single application of a stannous chloride-containing fluoride solution reduced enamel and dentine erosion up to 6 min and 3.5 min of constant acid flow, respectively

Substrate engagement of integrins α5 β1 and αv β3 is necessary, but not sufficient, for high directional persistence in migration on fibronectin

The interplay between specific integrin-mediated matrix adhesion and directional persistence in cell migration is not well understood. Here, we characterized fibroblast adhesion and migration on the extracellular matrix glycoproteins fibronectin and vitronectin, focusing on the role of α5 β1 and αv β3 integrins. Fibroblasts manifested high directional persistence in migration on fibronectin-, but not vitronectin-coated substrates, in a ligand density-dependent manner. Fibronectin stimulated α5 β1-dependent organization of the actin cytoskeleton into oriented, ventral stress fibers, and assembly of dynamic, polarized protrusions, characterized as regions free of stress fibers and rich in nascent adhesions at their edge. Such protrusions correlated with persistent, local leading edge advancement, but were not sufficient, nor necessary for directional migration over longer times. Selective blocking of αv β3 or α5 β1 integrins using small molecule integrin antagonists reduced directional persistence on fibronectin, indicating integrin cooperativity in maintaining directionality. On the other hand, patterned substrates, designed to selectively engage either integrin, or their combination, were not sufficient to establish directional migration. Overall, our study demonstrates adhesive coating-dependent regulation of directional persistence in fibroblast migration and challenges the generality of the previously suggested role of β1 and β3 integrins in directional migration.Instituto de Investigaciones Fisicoquímicas Teóricas y AplicadasConsejo Nacional de Investigaciones Científicas y Técnica

Substrate engagement of integrins α5 β1 and αv β3 is necessary, but not sufficient, for high directional persistence in migration on fibronectin

The interplay between specific integrin-mediated matrix adhesion and directional persistence in cell migration is not well understood. Here, we characterized fibroblast adhesion and migration on the extracellular matrix glycoproteins fibronectin and vitronectin, focusing on the role of α5 β1 and αv β3 integrins. Fibroblasts manifested high directional persistence in migration on fibronectin-, but not vitronectin-coated substrates, in a ligand density-dependent manner. Fibronectin stimulated α5 β1-dependent organization of the actin cytoskeleton into oriented, ventral stress fibers, and assembly of dynamic, polarized protrusions, characterized as regions free of stress fibers and rich in nascent adhesions at their edge. Such protrusions correlated with persistent, local leading edge advancement, but were not sufficient, nor necessary for directional migration over longer times. Selective blocking of αv β3 or α5 β1 integrins using small molecule integrin antagonists reduced directional persistence on fibronectin, indicating integrin cooperativity in maintaining directionality. On the other hand, patterned substrates, designed to selectively engage either integrin, or their combination, were not sufficient to establish directional migration. Overall, our study demonstrates adhesive coating-dependent regulation of directional persistence in fibroblast migration and challenges the generality of the previously suggested role of β1 and β3 integrins in directional migration.Instituto de Investigaciones Fisicoquímicas Teóricas y AplicadasConsejo Nacional de Investigaciones Científicas y Técnica

Standardized Diagnostics Including PET-CT Imaging, Bilateral Tonsillectomy and Neck Dissection Followed by Risk-Adapted Post-Operative Treatment Favoring Radio-Chemotherapy Improve Survival of Neck Squamous Cell Carcinoma of Unknown Primary Patients

Background: About five to 10% of cancers in the head and neck region are neck squamous cell carcinoma of unknown primary (NSCCUP). Their diagnosis and treatment are challenging given the risk of missing occult tumors and potential relapse. Recently, we described human papillomavirus (HPV)-related NSCCUP-patients (NSCCUP-P) as a subgroup with superior survival. However, standardized diagnostic workup, novel diagnostic procedures, decision-making in the multidisciplinary tumor board (MDTB) and multimodal therapy including surgery and post-operative radio-chemotherapy (PORCT) may also improve survival. Methods: For assessing the impact of standardized diagnostic processes simultaneously established with the MDTB on outcome, we split our sample of 115 NSCCUP-P into two cohorts treated with curative intent from 1988 to 2006 (cohort 1; n = 53) and 2007 to 2018 (cohort 2; n = 62). We compared diagnostic processes and utilized treatment modalities applying Chi-square tests, and outcome by Kaplan–Meier plots and Cox regression. Results: In cohort 2, the standardized processes (regular use of [18F]-FDG-PET-CT imaging followed by examination under anesthesia, EUA, bilateral tonsillectomy and neck dissection, ND, at least of the affected site) improved detection of primaries (P = 0.026) mostly located in the oropharynx (P = 0.001). From 66.0 to 87.1% increased ND frequency (P = 0.007) increased the detection of extracapsular extension of neck nodes (ECE+) forcing risk factor-adapted treatment by increased utilization of cisplatin-based PORCT that improved 5-years progression-free and overall survival from 60.4 and 45.3 to 67.7% (P = 0.411) and 66.1% (P = 0.025). Conclusions: Standardized diagnostic workup followed by ND and risk-factor adapted therapy improves survival of NSCCUP-P

Application of cerium chloride to improve the acid resistance of dentine

OBJECTIVE: To investigate the effect of cerium chloride, cerium chloride/fluoride and fluoride application on calcium release during erosion of treated dentine. METHODS: Forty dentine samples were prepared from human premolars and randomly assigned to four groups (1-4). Samples were treated twice a day for 5 days, 30s each, with the following solutions: group 1 placebo, group 2 fluoride (Elmex fluid), group 3 cerium chloride and group 4 combined fluoride and cerium chloride. For the determination of acid resistance, the samples were consecutively eroded six times for 5 min with lactic acid (pH 3.0) and the calcium release in the acid was determined. Furthermore, six additional samples per group were prepared and used for EDS analysis. SEM pictures of these samples of each group were also captured. RESULTS: Samples of group 1 presented the highest calcium release when compared with the samples of groups 2-4. The highest acid resistance was observed for group 2. Calcium release in group 3 was similar to that of group 4 for the first two erosive attacks, after which calcium release in group 4 was lower than that of group 3. Generally, the SEM pictures showed a surface coating for groups 2-4. No deposits were observed in group 1. CONCLUSION: Although fluoride showed the best protective effect, cerium chloride was also able to reduce the acid susceptibility of dentine significantly, which merits further investigation

Integrating movement ecology with biodiversity research - exploring new avenues to address spatiotemporal biodiversity dynamics

Movement of organisms is one of the key mechanisms shaping biodiversity, e.g. the distribution of genes, individuals and species in space and time. Recent technological and conceptual advances have improved our ability to assess the causes and consequences of individual movement, and led to the emergence of the new field of ‘movement ecology’. Here, we outline how movement ecology can contribute to the broad field of biodiversity research, i.e. the study of processes and patterns of life among and across different scales, from genes to ecosystems, and we propose a conceptual framework linking these hitherto largely separated fields of research. Our framework builds on the concept of movement ecology for individuals, and demonstrates its importance for linking individual organismal movement with biodiversity. First, organismal movements can provide ‘mobile links’ between habitats or ecosystems, thereby connecting resources, genes, and processes among otherwise separate locations. Understanding these mobile links and their impact on biodiversity will be facilitated by movement ecology, because mobile links can be created by different modes of movement (i.e., foraging, dispersal, migration) that relate to different spatiotemporal scales and have differential effects on biodiversity. Second, organismal movements can also mediate coexistence in communities, through ‘equalizing’ and ‘stabilizing’ mechanisms. This novel integrated framework provides a conceptual starting point for a better understanding of biodiversity dynamics in light of individual movement and space-use behavior across spatiotemporal scales. By illustrating this framework with examples, we argue that the integration of movement ecology and biodiversity research will also enhance our ability to conserve diversity at the genetic, species, and ecosystem levels

UBA6 and NDFIP1 regulate the degradation of ferroportin

Hepcidin regulates iron homeostasis by controlling the level of ferroportin, the only membrane channel that facilitates export of iron from within cells. Binding of hepcidin to ferroportin induces the ubiquitination of ferroportin at multiple lysine residues and subsequently causes the internalization and degradation of the ligand-channel complex within lysosomes. The objective of this study was to identify components of the ubiquitin system that are involved in ferroportin degradation. A HepG2 cell line, which inducibly expresses ferroportingreen fluorescent protein (FPN-GFP), was established to test the ability of small interfering (siRNA) directed against components of the ubiquitin system to prevent BMP6- and exogenous hepcidin-induced ferroportin degradation. Of the 88 siRNA directed against components of the ubiquitin pathway that were tested, siRNA-mediated depletion of the alternative E1 enzyme UBA6 as well as the adaptor protein NDFIP1 prevented BMP6- and hepcidin-induced degradation of ferroportin in vitro. A third component of the ubiquitin pathway, ARIH1, indirectly inhibited ferroportin degradation by impairing BMP6-mediated induction of hepcidin. In mice, the AAV-mediated silencing of Ndfip1 in the murine liver increased the level of hepatic ferroportin and increased circulating iron. The results suggest that the E1 enzyme UBA6 and the adaptor protein NDFIP1 are involved in iron homeostasis by regulating the degradation of ferroportin. These specific components of the ubiquitin system may be promising targets for the treatment of iron-related diseases, including iron overload and anemia of inflammation