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Many scientists, academic and clinical psychiatrists have contributed to the search for the biological basis of mental illness, leading to many notable discoveries and advances in understanding schizophrenia. Randomised controlled trials (RCTs) have established beyond reasonable doubt the efficacy of antidepressants, electroconvulsive therapy (ECT), antipsychotics and mood stabilisers. The most striking diagnostic advances have been made in identifying the genetics of learning disability and in developing neuroimaging and blood-based biomarkers of dementia. Polygenic risk scores and machine learning of neuroimaging and other data have real potential to impact upon clinical practice and improve patient care. Psychiatrists and indeed all those affected by mental illness should call for increased funding to identify biomarkers, develop new treatments and improve services.
In this essay, I first discuss the necessity of examining the history of peacebuilding from an evolutionary standpoint. In so doing, I compare my model to other paradigms and demonstrate that there are insights to be garnered from the peacebuilding behavior of nonhuman species, particularly when it comes to avoidance of conflict and reconciliation. However, I suggest that, at its base, the struggle for power between nonhuman species drives the pursuit of cooperation, the dominance hierarchy (in the case of the primates), a reflection of power as a means to an end, which in this case is group survival. I conclude with some thoughts about the implications my theory has for understanding other schools of thought in IR theory as well as peacebuilding policy and practice.
Tumors, trauma, and congenital defects require volume restoration of soft tissues. Tissue engineering provides an alternative source for substituting these defects. Cell encapsulation into hydrogels provides a three-dimensional microenvironment. Spheroids of cells provide close packing and increase cell-to-cell contacts resulting in differentiation. Gelatin is a natural polymer with low immunogenicity and preserved amino acid motifs for cell adhesion and proliferation. In the present study, a soft photo-crosslinked gelatin methacrylate (GelMA) hydrogel with long in vitro lifetime was synthesized. Stem cells (dental pulp derived, DPSC) and endothelial cells (umbilical cord derived, HUVEC) were formed into spheroids to induce prevascular network formation and encapsulated into GelMA (10% weight/volume). Results showed high cell viability, better gel mechanical properties, and longer HUVEC sprouting with spheroids compared to the same combination of cells. Altogether, the photo-crosslinked GelMA hydrogels with DPSC and HUVEC spheroids provided a promising tissue engineering and vascularization strategy in vitro.
America’s entrepreneurial culture is important because it promotes the search for new opportunities for innovation. Here, the author traces that culture through two industrial revolutions and focuses on the growing tension between entrepreneurship and bureaucracy inside and outside of the nation’s twentieth-century firms. Business histories are explored using categories adapted from behavioral economics. Particular attention is devoted to some of the important exceptions that throw light upon the stereotypes of the static government agency and the slow-moving industrial firm. Still, the author concludes, following World War II the economy had to be pulled out of its bureaucratic doldrums by new science- and social science-based industries that invigorated the nation’s entrepreneurial culture and promoted a wave of significant biological and digital innovations. The article concludes with a glance at the future of the bureaucratic and entrepreneurial cultures.
Chemical, biological, and radiological (CBR) terrorism continues to be a global threat. Studies examining global and historical toxicological characteristics of CBR terrorism are lacking.
Global Terrorism Database (GTD) and RAND Database of Worldwide Terrorism Incidents (RDWTI) were searched for CBR terrorist attacks from 1970 through 2017. Events fulfilling terrorism and poisoning definitions were included. Variables of event date and location, event realization, poisonous agent type, poisoning agent, exposure route, targets, connected events, additional means of harm, disguise methods, poisonings, and casualties were analyzed along with time trends and data gaps.
A total of 446 events of CBR terrorism were included from all world regions. A trend for increased number of events over time was observed (R2 = 0.727; coefficient = 0.511). In these attacks, 4,093 people lost their lives and 31,903 were injured. Chemicals were the most commonly used type of poison (63.5%). The most commonly used poisonous agents were acids (12.3%), chlorine or chlorine compounds (11.2%), riot control agents (10.8%), cyanides (5.8%), and Bacillus anthracis (4.9%). Occurrence of poisoning was confirmed in 208 events (46.6%). Most common exposure routes were skin, mucosa, or eye (57.2%) and inhalation (47.5%). Poison was delivered with additional means of harm in 151 events (33.9%) and in a disguised way in 214 events (48.0%), respectively.
This study showed that CBR terrorism is an on-going and increasingly recorded global threat involving diverse groups of poisons with additional harmful mechanisms and disguise. Industrial chemicals were used in chemical attacks. Vigilance and preparedness are needed for future CBR threats.
Chalcopyrite quantum dots (QDs) have emerged as a safe alternative to cadmium-based QDs for bio-applications. However, the research on AgInS2 chalcopyrite QDs has not been widely explored in terms of their toxicity. Herein, we report a synthesis of biocompatible AgInS2/ZnS QDs via a greener approach. The emission intensity of the as-synthesized AgInS2 core QDs was enhanced 2-fold after the ZnS shell growth. X-ray diffraction revealed the tetragonal crystal structure of QDs, and high-resolution transmission electron microscope images show that the QDs are spherical in shape and crystalline in nature. Cell viability assays conducted on different cell lines, such as HeLa, A549, and BHK-21 cells, indicated that AgInS2/ZnS QDs are least toxic at a QD concentration range of 100 µg/mL. The fluorescent microscope analysis of A549 cells incubated with AgInS2/ZnS QDs shows that the QDs were accumulated in the cell membranes. The as-synthesized AgInS2/ZnS QDs are less toxic and eco-friendly, and can be used for biolabeling.
The deliberate use of chemical, biological, radiological, and nuclear (CBRN) materials in war or terrorist attacks is perceived as a great threat globally. In the event of a release of CBRN agents, protection by means of medical countermeasures (MedCMs) could reduce health vulnerability. Nonetheless, for some diseases caused by these agents, innovative MedCMs do not exist and many of those that do might not be readily available. Inappropriate research and development funding and government procurement efforts can result in adverse economic consequences (eg, lost income, cost per loss of life, medical expenses) far exceeding the costs of strong and comprehensive preparedness initiatives. By illustrating factors of demand-side rationale for CBRN MedCMs, this article aims to strengthen integrity of policy-making associated with current demand requirements. Namely, an approach to inspire broader assessment is outlined by compiling and adapting existing economic models and concepts to characterize both soft and hard factors that influence demand-side rationale. First, the soft factor context is set by describing the impact of behavioral and political economics. Then, lessons learned from past public health funding models and associated collaborative access infrastructure are depicted to represent hard factors that can enhance the viability of MedCM preparedness evaluations.
The dynamic mechanical force transmitted through microenvironments during tissue formation and regeneration continuously impacts the mechanics of cells and thereby regulates gene and protein expression. The mechanical properties are altered during the process of stem cells differentiating into different lineages. At different stages of differentiation, stem cells display different mechanical properties in response to surrounding microenvironments, which depend on the subcellular structures, especially the cytoskeleton and nucleus. The mechanical properties of the cell nucleus affect protein folding and transport as well as the condensation of chromatin, through which the cell fate is regulated. These findings raise the question as to how cell mechanics change during differentiation. In this study, the mechanical properties of human bone marrow mesenchymal stem cells (hBMSCs) were determined during adipogenic and osteogenic differentiation by atomic force microscopy (AFM). The cytoskeletal structure and the modification of histone were investigated using laser confocal microscope and flow cytometry. The mechanical properties of cell nuclei at different stages of cell differentiation were compared. The stiffness of nuclei increased with time as osteogenesis was induced in hBMSCs. The H3K27me3 level increased during osteogenesis and adipogenesis according to flow cytometry analysis. Our results show conclusively that AFM is a facile and effective method to monitor stem cell differentiation. The measurement of cell mechanical properties by AFM improves our understanding on the connection between mechanics and stem cell fate.
With their abilities of self-renewal and pluripotency to differentiate into all three germ layers, human induced pluripotent stem cells (hiPSCs) are a promising cell source for cell-based drug and implant testing. However, the large-scale expansion and maintenance of hiPSCs requires following strict protocols. There is high demand for advanced cell culture systems capable of generating high-quality hiPSCs to meet application requirements. In this study, we probe the possibility of modifying polymeric substrates for maintaining the self-renewal and pluripotency of hiPSCs. Here, polydopamine (PDA) was employed to immobilize the Laminin 521 (LN521) onto the surface of polyethylene terephthalate (PET). An aqueous solution of dopamine with concentrations ranging from 0 to 2.0 mg/mL was applied on PET surfaces. These PDA-modified surfaces were further functionalized with LN521. Surface wettability was evaluated by measuring the water contact angle (WCA) and surface properties of the modified substrate were analyzed using an atomic force microscope (AFM). Initial hiPSC attachment (1h after seeding) and cell proliferation were evaluated by counting the total cell number. The maintenance of pluripotency was evaluated at designed time points. WCA of the PDA-LN521 surfaces gradually decreased from 62.1°±6.3° to 8.1°±2.9°. The maximum peak-to-valley height roughness (Rt) of those surfaces determined by AFM increased in a dopamine-concentration-dependent manner, ranging from 43.9±1.6 nm to 126.7±7.6 nm. The Young’s modulus of these surfaces was substantially increased from 0.98±0.36 GPa to 4.81±2.41 GPa. There was a significant enhancement (13.0±7.2% and 24.2±8.1%) of hiPSC adhesion on PDA-LN521 (dopamine concentration at 0.125 and 0.25 mg/mL). When increasing the dopamine concentration to 0.5 and 1.0 mg/mL, there was no further increase in hiPSC adhesion on PDA-LN521 surfaces. Moreover, hiPSC proliferation was remarkably enhanced on PDA-LN521 surface (dopamine solution at concentration from 0.125 to 1.0 mg/mL). Pluripotency of hiPSCs was not affected by PDA treatment. In conclusion, PDA-mediated surface modification is an effective approach for the robust expansion and maintenance of hiPSCs on polymer substrates.
A fundamental design rule that nature has developed for biological machines is the intimate correlation between motion and function. One class of biological machines is molecular motors in living cells, which directly convert chemical energy into mechanical work. They coexist in every eukaryotic cell, but differ in their types of motion, the filaments they bind to, the cargos they carry, as well as the work they perform. Such natural structures offer inspiration and blueprints for constructing DNA-assembled artificial systems, which mimic their functionality. In this article, we describe two groups of cytoskeletal motors, linear and rotary motors. We discuss how their artificial analogues can be built using DNA nanotechnology. Finally, we summarize ongoing research directions and conclude that DNA origami has a bright future ahead.
In this work, flavonoids in Polygonum cuspidatum Sieb. et Zucc. were extracted by ultrasound-assisted methodology and determined by ultraviolet–visible spectrophotometry. After that, extraction conditions were optimized by the single fact investigation, the central composite design, and response surface methodology (RSM) in turn. The results showed the optimal values of ethanol concentration, solid–liquid ratio, extraction temperature, extraction time, ultrasonic power, and number of extraction times were 60%, 1:20 (g/mL), 45 °C, 34 min; 80 W, and 5, respectively. The extraction ratio of flavonoids could be as high as 94.50%. The influence order of each factor was ultrasonic power > extraction time > extraction temperature > ethanol concentration. The results also showed that the experimental value was close to the predicted value (94.49%) of the established model by RSM, which proved that the established model was reasonable. The thermodynamic results showed that the extraction process was endothermic and could proceed spontaneously.
Nature’s optical nanomaterials are poised to form the platform for future optical devices with unprecedented functionality. The brilliant colors of many animals arise from the physical interaction of light with nanostructured, multifunctional materials. While their length scale is typically in the 100-nm range, the morphology of these structures can vary strongly. These biological nanostructures are obtained in a controlled manner, using biomaterials under ambient conditions. The formation processes nature employs use elements of both equilibrium self-assembly and far-from-equilibrium and growth processes. This renders not only the colors themselves, but also the formation processes technologically and ecologically highly relevant. Yet, for many biological nanostructured materials, little is known about the formation mechanisms—partially due to a lack of in vivo imaging methods. Here, we present the toolbox of natural multifunctional nanostructures and the current knowledge about the understanding of their far-from-equilibrium assembly processes.
Periodontitis, or conventionally “Gum Disease,” is the infection and inflammation of gingival tissue, and is currently the leading cause of tooth loss in the United States. One of the most effective treatments of periodontitis is guided bone regeneration (GBR); however, current GBR barrier membranes lack high biocompatibility and cell impermeability. The authors of this study evaluated the in vitro viability of previously synthesized Gelatin-Pluronic® F127 hybrid hydrogels as potential GBR barrier membranes through a novel three-partition test involving migration of fluorescent-dyed human dermal fibroblasts. Results showed that cells were unable to migrate across the Gelatin-Pluronic® F127 hybrid hydrogel barrier, whereas control setups with gelatin hydrogel barriers showed cell permeability. In addition, cytotoxicity tests were conducted with fibroblasts plated in both cell mediums that had been incubated while in contact hybrid gels and cell mediums suspended on the surface of hybrid gels during swelling procedures. Fluorescence cell plate readings showed similar cell viability across data from both tests, indicating that Gelatin-Pluronic® F127 hybrid hydrogels are not toxic to cells, and thus biocompatible.
To research the impact of the shape on the assembly of the natural objects (protein, virus, bacteria, living cells) the polymer microcapsules with similar surface chemistry and different by shape (spherical, cubical and tetrahedral) had been synthesized. It was found that the energetically favourable face-to-face attachment of anisotropic microcapsules drives the formation of stable and compacted assembly while isotropic microcapsules assembly is mobile and chain-like structures with a point like a contact area. The difference in assembling behaviour of anisotropic (cubic, tetrahedral) and isotropic (spherical) microparticles is related to the fact that the interfacial hydrophobic energies between the anisotropic microparticles are 6-4 orders of magnitude higher than that for the isotropic microparticles due to the significantly higher contact area of anisotropic microparticles. Such mimicking of the natural objects by polymer microcapsules and research their interaction driven by shape explains the arrangements of isotropic and anisotropic cells in bacteria and its mobility.
A hallmark of life is plasticity, which enables reproduction, evolution, and environmental adaptivity. It is natural to wonder if these remarkable features in nature and biology can be realized in the materials world and implemented in the emerging fields of autonomous systems, artificial intelligence, and animal–machine interfaces. First, we describe fundamental features of neurons and synapses in the brain that are responsible for information processing. Then we discuss mechanisms governing electronic plasticity in correlated electronic quantum materials that mimic organismic behavior. We give examples of learning networks and circuits designed using quantum materials that can be implemented for machine intelligence. We conclude with suggestions for future interdisciplinary research wherein synergistic interactions between orbital filling, defects, and strain could give rise to new functionality of relevance to sensory interfaces (e.g., haptics), neural information processing, and neuroscience.
The polysaccharide alginate has received most extensive attention as bioink in bioprinting applications due to its ability to undergo gelation under cell-friendly conditions. However, absence of cell-binding motifs and the erratic degradation of alginate hydrogels have remained their persistent limitations. Honey is a conveniently available natural material, known for its role in wound healing and skin tissue regeneration. However, honey blending to improve biological response of alginate-based bioprinted scaffolds has not been yet reported. In the present work, honey-alginate bioinks were evaluated for their printability property (shape fidelity). It was found that honey blending reduced alginate viscosity, which gradually affected bioprinting fidelity. Therefore, the concentration that provides for acceptable bioprinting along with improvement in cell proliferations is determined. It is concluded that honey blending improves cell response of alginate bioinks and can be a facile approach to obtain bioinks especially for in situ skin tissue engineering applications.
Mechanical properties of neurons represent a key factor that determines the functionality of neuronal cells and the formation of neural networks. The main source of mechanical stability for the cell is a biopolymer network of microtubules and actin filaments that form the main components of the cellular cytoskeleton. This biopolymer network is responsible for the growth of neuronal cells as they extend neurites to connect with other neurons, forming the nervous system. Here we present experimental results that combine atomic force microscopy (AFM) and fluorescence microscopy to produce systematic, high-resolution elasticity and fluorescence maps of cortical neurons. This approach allows us to apply external forces to neurons, and to monitor the dynamics of the cell cytoskeleton. We measure how the elastic modulus of neurons changes upon changing the ambient temperature, and identify the cytoskeletal components responsible for these changes. These results demonstrate the importance of taking into account the effect of ambient temperature when measuring the mechanical properties of cells.
Graphene and graphene oxide are being investigated for use in drug delivery systems, bioimaging, and antimicrobial applications. However, their effects, if any, on healthy cells need to be established before they can be deemed safe for therapeutic use. This research tested whether graphene oxide (GO) and/or partially reduced graphene oxide (pRGO) exhibit antimicrobial properties on Staphylococcus aureus; and also examined the growth and proliferation of dermal fibroblasts and keratinocytes in media modified with graphene oxide or partially reduced graphene oxide. Staphylococcus aureus was able to proliferate in both GO and pRGO- modified growth media as well as on gelatin made with GO and pRGO solutions. Both GO and pRGO increased dermal fibroblast doubling time and displayed lower cell counts compared to the control, with pRGO exerting a more pronounced effect than GO. After 4 days of keratinocyte incubation, GO and pRGO showed cell counts 75-80% less than the control. Cell counts of test samples dropped even lower by day 5 while the control cell count increased, suggesting that more investigation into the properties as well as the safety of graphene and its derivatives needs to be done before it is implemented for medical applications.
We define Regenerative Engineering as a Convergence of Advanced Materials Science, Stem Cell Science, Physics, Developmental Biology, and Clinical Translation. We believe that an “un-siloed’ technology approach will be important in the future to realize grand challenges such as limb and organ regeneration. We also believe that biomaterials will play a key role in achieving overall translational goals. Through convergence of a number of technologies, with advanced materials science playing an important role, we believe the prospect of engaging future grand challenges is possible. Regenerative Engineering as a field is particularly suited for solving clinical problems that are relevant today. The paradigms utilized can be applied to the regeneration of tissue in the shoulder where tendon and muscle currently have low levels of regenerative capability, and the consequences, especially in alternative surgical solutions for massive tendon and muscle loss at the shoulder have demonstrated significant morbidity. Polymer, polymer-cell, and polymer biological factor, and polymer-physical systems can be utilized to propose a range of solutions to shoulder tissue regeneration. The approaches, possibilities, limitations and future strategies, allow for a variety of clinical solutions in musculoskeletal disease treatment.