Nested structure role in the mechanical response of spicule inspired fibers.

Euplectella aspergillummarine sponge spicules are renowned for their remarkable strength and toughness. These spicules exhibit a unique concentric layering structure, which contributes to their exceptional mechanical resistance. In this study, finite element method simulations were used to comprehensively investigate the effect of nested cylindrical structures on the mechanical properties of spicules. This investigation leveraged scanning electron microscopy images to guide the computational modeling of the microstructure and the results were validated by three-point bending tests of 3D-printed spicule-inspired structures. The numerical analyses showed that the nested structure of spicules induces stress and strain jumps on the layer interfaces, reducing the load on critical zones of the fiber and increasing its toughness. It was found that this effect shows a tapering enhancement as the number of layers increases, which combines with a threshold related to the 3D-printing manufacturability to suggest a compromise for optimal performance. A comprehensive evaluation of the mechanical properties of these fibers can assist in developing a new generation of bioinspired structures with practical real-world applications.

Factors impacting community living outcomes among former long-term nursing home residents using the interdependence-Human Activity Assistive Technology (i-HAAT) model.

Despite an increased application of social theory in assistive technology (AT) outcomes research, there continues to be a gap in integrating AT conceptual models in research design, data analysis, and results interpretation. This paper merged two preexisting AT models, the Human Activity Assistive Technology model (HAAT) and the interdependence frame for AT into a novel framework, the interdependence-HAAT model (i-HAAT). This model was used to examine the outcomes of former long-term nursing home residents using AT. The model was also used as a framework to facilitate quantitative variable identification and categorization, emphasize the interconnectivity between domain variables, and explore the infrastructural supports necessary for the successful community reintegration of deinstitutionalized AT users. Meaningful integration of theory into practice is the essential next step in generating socially responsive research that addresses AT consumer needs and moves the field forward.

Estrogen-dependent association of HDAC4 with fear in female mice and women with PTSD.

Women are at increased risk of developing post-traumatic stress disorder (PTSD) following a traumatic event. Recent studies suggest that this may be mediated, in part, by circulating estrogen levels. This study evaluated the hypothesis that individual variation in response to estrogen levels contributes to fear regulation and PTSD risk in women. We evaluated DNA methylation from blood of female participants in the Grady Trauma Project and found that serum estradiol levels associates with DNA methylation across the genome. For genes expressed in blood, we examined the association between each CpG site and PTSD diagnosis using linear models that adjusted for cell proportions and age. After multiple test correction, PTSD associated with methylation of CpG sites in the HDAC4 gene, which encodes histone deacetylase 4, and is involved in long-term memory formation and behavior. DNA methylation of HDAC4 CpG sites were tagged by a nearby single-nucleotide polymorphism (rs7570903), which also associated with HDAC4 expression, fear-potentiated startle and resting-state functional connectivity of the amygdala in traumatized humans. Using auditory Pavlovian fear conditioning in a rodent model, we examined the regulation of Hdac4 in the amygdala of ovariectomized (OVX) female mice. Hdac4 messenger RNA levels were higher in the amygdala 2 h after tone-shock presentations, compared with OVX-homecage control females. In naturally cycling females, tone-shock presentations increased Hdac4 expression relative to homecage controls for metestrous (low estrogen) but not the proestrous (high estrogen) group. Together, these results support an estrogenic influence of HDAC4 regulation and expression that may contribute to PTSD in women.

Histologic tissue response to furcation perforation repair using mineral trioxide aggregate or dental pulp stem cells loaded onto treated dentin matrix or tricalcium phosphate.

OBJECTIVES: The aim of this study is to compare the effect of treated dentine matrix (TDM) and tricalcium phosphate (TCP) scaffolds on odontogenic differentiation and mineralization of dental pulp stem cells (DPSCs) in furcation perforations created in the pulp chamber floor of premolar teeth in dogs. MATERIAL AND METHODS: DPSCs were isolated and cultured from the dental pulp of the maxillary left second and third premolars of dogs. The DPSCs were loaded on TCP (SC+TCP) and TDM (SC+TDM) scaffolds and inserted into intentionally perforated pulp chamber floors of premolars in dogs; six teeth were used for each group. Three more groups of six specimens were created, and mineral trioxide aggregate (MTA), TDM, and TCP were inserted into the perforations to act as controls. An intact premolar and no treatment in the perforation site were used as positive and negative controls respectively. After 3 months, the animals were sacrificed and the type of inflammation, presence of dentine, continuation and type of cementum, type of connective tissue, and presence of foreign body reaction were evaluated, and significant differences were between groups determined using the Fisher's exact test. The evaluation of the amount of inflammation and the percentage of new bone formation was evaluated using the Mann-Whitney U test. RESULTS: The negative control group was associated with severe inflammation and granulation tissue formation. In the positive control group, intact periodontal tissues and no inflammation were observed. Dentine bridge formation was not seen in specimens of any group. The specimens in the SC+TDM group were associated with significantly more bone formation than other groups (P < 0.001). The amount of inflammation was less than 10 % in specimens of all groups with the exception of three specimens in the TCP group that were categorized as 10-30 %. Chronic inflammation without foreign body reactions was the major pattern of inflammation in groups. Formation of cementum with a cellular and continuous appearance was seen in all specimens. CONCLUSIONS: SC+TDM was associated with significantly more bone formation when used to repair uninfected furcation perforations in the premolar teeth of dogs. CLINICAL RELEVANCE: Application of TDM as a biological scaffold in combination with DPSCs may offer an advantage during the repair of root perforation defects.

Binding assessment of two arachidonic-based synthetic derivatives of adrenalin with ß-lactoglobulin: Molecular modeling and chemometrics approach.

A computational approach to predict the main binding modes of two adrenalin derivatives, arachidonoyl adrenalin (AA-AD) and arachidonoyl noradrenalin (AA-NOR) with the ß-lactoglubuline (BLG) as a nano-milk protein carrier is presented and assessed by comparison to the UV-Vis absorption spectroscopic data using chemometric analysis. Analysis of the spectral data matrices by using the multivariate curve resolution-alternating least squares (MCR-ALS) algorithm led to the pure concentration calculation and spectral profiles resolution of the chemical constituents and the apparent equilibrium constants computation. The negative values of entropy and enthalpy changes for both compound indicated the essential role of hydrogen bonding and van der Waals interactions as main driving forces in stabilizing protein-ligand complex. Computational studies predicted that both derivatives are situated in the calyx pose and remained in that pose during the whole time of simulation with no any significant protein structural changes which pointed that the BLG could be considered as a suitable carrier for these catecholamine compounds.

Computational design of Tryprostatin-A derivatives as novel αß-tubulin inhibitors.

In the first part of this work, binding energies, inhibition constants and binding modes for a group of previously synthesized Tryprostatin-A (TPS-A) derivatives at the binding site of αß-tubulin have been comprehensively investigated by molecular docking study. The results represent relatively suitable binding energies for these inhibitors in the αß-tubulin binding site. In the second part, docking tools were utilized in order to design a group of novel analogues of TPS-A. The results of molecular docking reveal that these newly designed molecules have relatively lower binding energies in the pocket of αß-tubulin. Compound 26 resulted as the best docked molecule with the highest binding affinity (binding energy of -10.74 kcal/mol and calculated inhibition constant of 13.44 nM). In the last part of this study, three representative complexes were subjected to a 25 ns molecular dynamics simulation to further validate the proposed binding modes and interactions. Analysis of the simulation trajectories showed that the root mean square deviation (RMSD) profile of compound 26 was fairly stable during the whole simulation time, indicating that the orientation generated from the docking study is fairly well preserved during the entire length of the simulation. Moreover, the RMSD profiles of compounds 4 and 31 were probably stable in relation to αß-tubulin after 7 and 14 ns, and these molecular systems were well behaved thereafter. The results of the current study shed some light on the binding mode of TPS-A analogues for further experimental studies.

A combined spectroscopic, docking and molecular dynamics simulation approach to probing binding of a Schiff base complex to human serum albumin.

The molecular mechanism of a Schiff base complex ((E)-((E)-2-(3-((E)-((E)-3(mercapto (methylthio) methylene)cyclopentylidene) amino) propylimino) cyclopentylidene) (methylthio) methanethiol) binding to Human Serum Albumin (HSA) was investigated by fluorescence quenching, absorption spectroscopy, molecular docking and molecular dynamics (MD) simulation procedures. The fluorescence emission of HSA was quenched by this Schiff base complex that has been analyzed for estimation of binding parameters. The titration of Schiff base solution by various amount of HSA was also followed by UV-Vis absorption spectroscopy and the corresponding data were analyzed by suitable models. The results revealed that this Schiff base has an ability to bind strongly to HSA and formed 1:1 complex. Energy transfer mechanism of quenching was discussed and the value of 5.45 ± 0.06 nm was calculated as the mean distance between the bound complex and the Trp residue. This is implying the high possibility of energy transfer from HSA to this Schiff base complex. Molecular docking results indicated that the main active binding site for this Schiff base complex is site III in subdomain IB. Moreover, MD simulation results suggested that this Schiff base complex can interact with HSA, without affecting the secondary structure of HSA but probably with a slight modification of its tertiary structure. MD simulations, molecular docking and experimental data reciprocally supported each other.

Attention bias toward threat is associated with exaggerated fear expression and impaired extinction in PTSD.

BACKGROUND: Post-traumatic stress disorder (PTSD) develops in a minority of traumatized individuals. Attention biases to threat and abnormalities in fear learning and extinction are processes likely to play a critical role in the creation and/or maintenance of PTSD symptomatology. However, the relationship between these processes has not been established, particularly in highly traumatized populations; understanding their interaction can help inform neural network models and treatments for PTSD. METHOD: Attention biases were measured using a dot probe task modified for use with our population; task stimuli included photographs of angry facial expressions, which are emotionally salient threat signals. A fear-potentiated startle paradigm was employed to measure atypical physiological response during acquisition and extinction phases of fear learning. These measures were administered to a sample of 64 minority (largely African American), highly traumatized individuals with and without PTSD. RESULTS: Participants with PTSD demonstrated attention biases toward threat; this attentional style was associated with exaggerated startle response during fear learning and early and middle phases of extinction, even after accounting for the effects of trauma exposure. CONCLUSIONS: Our findings indicate that an attentional bias toward threat is associated with abnormalities in 'fear load' in PTSD, providing seminal evidence for an interaction between these two processes. Future research combining these behavioral and psychophysiological techniques with neuroimaging will be useful toward addressing how one process may modulate the other and understanding whether these phenomena are manifestations of dysfunction within a shared neural network. Ultimately, this may serve to inform PTSD treatments specifically designed to correct these atypical processes.