Thermodynamic Selection of Steric Zipper Patterns in the Amyloid Cross-β Spine

At the core of amyloid fibrils is the cross-β spine, a long tape of β-sheets formed by the constituent proteins. Recent high-resolution x-ray studies show that the unit of this filamentous structure is a β-sheet bilayer with side chains within the bilayer forming a tightly interdigitating “steric zipper” interface. However, for a given peptide, different bilayer patterns are possible, and no quantitative explanation exists regarding which pattern is selected or under what condition there can be more than one pattern observed, exhibiting molecular polymorphism. We address the structural selection mechanism by performing molecular dynamics simulations to calculate the free energy of incorporating a peptide monomer into a β-sheet bilayer. We test filaments formed by several types of peptides including GNNQQNY, NNQQ, VEALYL, KLVFFAE and STVIIE, and find that the patterns with the lowest binding free energy correspond to available atomistic structures with high accuracy. Molecular polymorphism, as exhibited by NNQQ, is likely because there are more than one most stable structures whose binding free energies differ by less than the thermal energy. Detailed analysis of individual energy terms reveals that these short peptides are not strained nor do they lose much conformational entropy upon incorporating into a β-sheet bilayer. The selection of a bilayer pattern is determined mainly by the van der Waals and hydrophobic forces as a quantitative measure of shape complementarity among side chains between the β-sheets. The requirement for self-complementary steric zipper formation supports that amyloid fibrils form more easily among similar or same sequences, and it also makes parallel β-sheets generally preferred over anti-parallel ones. But the presence of charged side chains appears to kinetically drive anti-parallel β-sheets to form at early stages of assembly, after which the bilayer formation is likely driven by energetics

Correlation between clinical performance and degree of conversion of resin cements: a literature review

AbstractResin-based cements have been frequently employed in clinical practice to lute indirect restorations. However, there are numerous factors that may compromise the clinical performance of those cements. The aim of this literature review is to present and discuss some of the clinical factors that may affect the performance of current resin-based luting systems. Resin cements may have three different curing mechanisms: chemical curing, photo curing or a combination of both. Chemically cured systems are recommended to be used under opaque or thick restorations, due to the reduced access of the light. Photo-cured cements are mainly indicated for translucent veneers, due to the possibility of light transmission through the restoration. Dual-cured are more versatile systems and, theoretically, can be used in either situation, since the presence of both curing mechanisms might guarantee a high degree of conversion (DC) under every condition. However, it has been demonstrated that clinical procedures and characteristics of the materials may have many different implications in the DC of currently available resin cements, affecting their mechanical properties, bond strength to the substrate and the esthetic results of the restoration. Factors such as curing mechanism, choice of adhesive system, indirect restorative material and light-curing device may affect the degree of conversion of the cement and, therefore, have an effect on the clinical performance of resin-based cements. Specific measures are to be taken to ensure a higher DC of the luting system to be used

A new era for understanding amyloid structures and disease

The aggregation of proteins into amyloid fibrils and their deposition into plaques and intracellular inclusions is the hallmark of amyloid disease. The accumulation and deposition of amyloid fibrils, collectively known as amyloidosis, is associated with many pathological conditions that can be associated with ageing, such as Alzheimer disease, Parkinson disease, type II diabetes and dialysis-related amyloidosis. However, elucidation of the atomic structure of amyloid fibrils formed from their intact protein precursors and how fibril formation relates to disease has remained elusive. Recent advances in structural biology techniques, including cryo-electron microscopy and solid-state NMR spectroscopy, have finally broken this impasse. The first near-atomic-resolution structures of amyloid fibrils formed in vitro, seeded from plaque material and analysed directly ex vivo are now available. The results reveal cross-β structures that are far more intricate than anticipated. Here, we describe these structures, highlighting their similarities and differences, and the basis for their toxicity. We discuss how amyloid structure may affect the ability of fibrils to spread to different sites in the cell and between organisms in a prion-like manner, along with their roles in disease. These molecular insights will aid in understanding the development and spread of amyloid diseases and are inspiring new strategies for therapeutic intervention

Use of elaborate feedback and an audience-response-system in dental education

Introduction: The aim of the study was to examine the effect of an elaborate feedback and an audience response system (ARS) on learning success. Methods: Students of the 1st clinical semester were randomly assigned to a study and a control group. The randomization was carried out considering the factors of age, gender and power spectrum during preliminary dental examination. Within 10 lectures 5 multiple-choice questions were asked about the learning objectives and answered by the students using an ARS. Only the study group received an immediate comprehensive feedback on the results. A final exam at the end was carried out in order to evaluate whether the elaborate feedback leads to a successful learning. Furthermore the effect of the ARS on the lecture atmosphere was investigated. Result: The results of the final exams showed no significant difference between the study and the control group regarding the learning success. Conclusion: Although no significant effect on learning success was found, the ARS creates a more interactive, positive learning environment.Einleitung: Die Studie soll die Frage klären, ob sich durch Anwendung von elaboriertem Feedback und einem Audience-Response-Systems (ARS) der Lernerfolg im Studienfach Zahnerhaltung signifikant verbessert. Methodik: Die Studierenden des 1. klinischen Semesters wurden in eine Studien- und eine Kontrollgruppe randomisiert eingeteilt. Die Randomisierung erfolgte unter Berücksichtigung der Faktoren Alter, Geschlecht und Note im Physikum. Im Verlauf von 10 Vorlesungen wurden pro Vorlesung 5 Multiple-Choice-Fragen zu den formulierten Lernzielen gestellt. Diese wurden unter Anwendung eines ARS von den Studierenden beantwortet. Nur die Studiengruppe erhielt sofort ein elaboriertes Feedback zu den Ergebnissen. Die am Ende durchgeführte Abschlussklausur und Evaluation sollten ermitteln, ob das elaborierte Feedback zu einem Lernerfolg führt und welchen Effekt das ARS auf die Vorlesungsatmosphäre hat. Ergebnisse: Die Ergebnisse der Abschlussklausuren ergaben keinen signifikanten Unterschied zwischen dem Lernerfolg der Studien- und der Kontrollgruppe. Schlussfolgerung: Durch das elaborierte Feedback zeigte sich in dieser Untersuchung kein Unterschied im Lernerfolg. Mit dem ARS ließ sich jedoch eine interaktivere, positivere Lernatmosphäre schaffen

Luting of CAD/CAM ceramic inlays: direct composite versus dual-cure luting cement

The aim of this study was to investigate bonding effectiveness in direct restorations. A two-step self-etch adhesive and a light-cure resin composite was compared with luting with a conventional dual-cure resin cement and a two-step etch and rinse adhesive. Class-I box-type cavities were prepared. Identical ceramic inlays were designed and fabricated with a computer-aided design/computer-aided manufacturing (CAD/CAM) device. The inlays were seated with Clearfil SE Bond/Clearfil AP-X (Kuraray Medical) or ExciTE F DSC/Variolink II (Ivoclar Vivadent), each by two operators (five teeth per group). The inlays were stored in water for one week at 37°C, whereafter micro-tensile bond strength testing was conducted. The micro-tensile bond strength of the direct composite was significantly higher than that from conventional luting, and was independent of the operator (P<0.0001). Pre-testing failures were only observed with the conventional method. High-power light-curing of a direct composite may be a viable alternative to luting lithium disilicate glass-ceramic CAD/CAM restorations.status: publishe