Most memories that are formed are forgotten, while others are retained longer and are subject to memory stabilization. We show that non-invasive transcutaneous electrical stimulation of the greater occipital nerve (NITESGON) using direct current during learning elicited a long-term memory effect. However, it did not trigger an immediate effect on learning. A neurobiological model of long-term memory proposes a mechanism by which memories that are initially unstable can be strengthened through subsequent novel experiences. In a series of studies, we demonstrate NITESGON's capability to boost the retention of memories when applied shortly before, during, or shortly after the time of learning by enhancing memory consolidation via activation and communication in and between the locus coeruleus pathway and hippocampus by plausibly modulating dopaminergic input. These findings may have a significant impact for neurocognitive disorders that inhibit memory consolidation such as Alzheimer's disease.
Learning , Memory Consolidation , Memory, Long-Term , Memory Consolidation/physiology , Hippocampus/physiology , Dopamine/pharmacology
OBJECTIVES: The aim of this study was to determine the presence of condylar spatial changes in patients having rapid maxillary expansion treatments compared to a control group. METHODS: Thirty-seven patients with maxillary transverse deficiency (11-17 years old) were randomly allocated into two groups (one treatment group - tooth borne expander [hyrax] - and one control group). Cone-beam computer tomographies (CBCT) were obtained from each patient at two time points (initial T1 and at removal of appliance at 6 months T2). CBCTs were analyzed using AVIZO software and landmarks were placed on the upper first molars and premolars, cranial base, condyles and glenoid fossa. Descriptive statistics, intraclass correlation coefficients and one-way Anova analysis were used to determine if there was a change in condyle position with respect to the glenoid fossa and cranial base and if there was a statistically significant difference between groups. RESULTS: Descriptive statistics show that changes in the condyle position with respect to the glenoid fossa were minor in both groups (<1.9mm average for both groups). The largest difference in both groups was found when measuring the distance between the left and right condyle heads. When comparing changes between both groups, no statistically significant difference was found between changes in the condyles (P<0.05). CONCLUSION: Rapid maxillary expansion treatments present mild effects/changes on the condylar position. Nevertheless, these changes do not present a significant difference with controls, thus not constituting a limitation for applying this treatment.
Mandibular Condyle/diagnostic imaging , Palatal Expansion Technique , Adolescent , Child , Cone-Beam Computed Tomography , Humans , Orthodontic Anchorage Procedures , Treatment Outcome
As DNA repair enzymes are essential for preserving genome integrity, understanding their substrate interaction dynamics and the regulation of their catalytic mechanisms is crucial. Using single-molecule imaging, we investigated the association and dissociation kinetics of the bipolar endonuclease NucS from Pyrococcus abyssi (Pab) on 5' and 3'-flap structures under various experimental conditions. We show that association of the PabNucS with ssDNA flaps is largely controlled by diffusion in the NucS-DNA energy landscape and does not require a free 5' or 3' extremity. On the other hand, NucS dissociation is independent of the flap length and thus independent of sliding on the single-stranded portion of the flapped DNA substrates. Our kinetic measurements have revealed previously unnoticed asymmetry in dissociation kinetics from these substrates that is markedly modulated by the replication clamp PCNA. We propose that the replication clamp PCNA enhances the cleavage specificity of NucS proteins by accelerating NucS loading at the ssDNA/dsDNA junctions and by minimizing the nuclease interaction time with its DNA substrate. Our data are also consistent with marked reorganization of ssDNA and nuclease domains occurring during NucS catalysis, and indicate that NucS binds its substrate directly at the ssDNA-dsDNA junction and then threads the ssDNA extremity into the catalytic site. The powerful techniques used here for probing the dynamics of DNA-enzyme binding at the single-molecule have provided new insight regarding substrate specificity of NucS nucleases.
Archaeal Proteins/metabolism , DNA, Single-Stranded/metabolism , DNA/metabolism , Flap Endonucleases/metabolism , Archaeal Proteins/chemistry , Catalytic Domain , DNA Replication , Flap Endonucleases/chemistry , Kinetics , Manganese/chemistry , Photobleaching , Proliferating Cell Nuclear Antigen/metabolism , Pyrococcus abyssi/enzymology , Substrate Specificity , Temperature , Viscosity
Although broadly admired for its aesthetic qualities, the art of origami is now being recognized also as a framework for mechanical metamaterial design. Working with the Miura-ori tessellation, we find that each unit cell of this crease pattern is mechanically bistable, and by switching between states, the compressive modulus of the overall structure can be rationally and reversibly tuned. By virtue of their interactions, these mechanically stable lattice defects also lead to emergent crystallographic structures such as vacancies, dislocations, and grain boundaries. Each of these structures comes from an arrangement of reversible folds, highlighting a connection between mechanical metamaterials and programmable matter. Given origami's scale-free geometric character, this framework for metamaterial design can be directly transferred to milli-, micro-, and nanometer-size systems.
