Our ability to acknowledge and recognize our own identity — our “self” — is a characteristic doubtless unique to humans. Where does this feeling come from? How does the combination of ...neurophysiological processes coupled with our interaction with the outside world construct this coherent identity? We know that our social interactions contribute via the eyes, ears, etc. However, our self is not only influenced by our senses. It is also influenced by the actions we perform and those we see others perform. Our brain anticipates the effects of our own actions and simulates the actions of others. In this way, we become able to understand ourselves and to understand the actions and emotions of others. This book describes the new field of “Motor Cognition”. Though motor actions have long been studied by neuroscientists and physiologists, it is only recently that scientists have considered the role of actions in building the self. How consciousness of action is part of self-consciousness, how one's own actions determine the sense of being an agent, how actions performed by others impact on ourselves for understanding others, differentiating ourselves from them and learning from them: these questions are raised and discussed throughout the book, drawing on experimental, clinical, and theoretical bases. The advent of new neuroscience techniques, such as neuroimaging and direct electrical brain stimulation, together with a renewal of behavioral methods in cognitive psychology, provide new insights into this area. Mental imagery of action, self-recognition, consciousness of actions, imitation can be objectively studied using these new tools. The results of these investigations shed light on clinical disorders in neurology, psychiatry, and in neuro-development.
Metallodrugs in cancer nanomedicine Peña, Quim; Wang, Alec; Zaremba, Orysia ...
Chemical Society reviews,
04/2022, Volume:
51, Issue:
7
Journal Article
Peer reviewed
Metal complexes are extensively used for cancer therapy. The multiple variables available for tuning (metal, ligand, and metal-ligand interaction) offer unique opportunities for drug design, and have ...led to a vast portfolio of metallodrugs that can display a higher diversity of functions and mechanisms of action with respect to pure organic structures. Clinically approved metallodrugs, such as cisplatin, carboplatin and oxaliplatin, are used to treat many types of cancer and play prominent roles in combination regimens, including with immunotherapy. However, metallodrugs generally suffer from poor pharmacokinetics, low levels of target site accumulation, metal-mediated off-target reactivity and development of drug resistance, which can all limit their efficacy and clinical translation. Nanomedicine has arisen as a powerful tool to help overcome these shortcomings. Several nanoformulations have already significantly improved the efficacy and reduced the toxicity of (chemo-)therapeutic drugs, including some promising metallodrug-containing nanomedicines currently in clinical trials. In this critical review, we analyse the opportunities and clinical challenges of metallodrugs, and we assess the advantages and limitations of metallodrug delivery, both from a nanocarrier and from a metal-nano interaction perspective. We describe the latest and most relevant nanomedicine formulations developed for metal complexes, and we discuss how the rational combination of coordination chemistry with nanomedicine technology can assist in promoting the clinical translation of metallodrugs.
Heme-copper oxidases (HCOs) are terminal enzymes on the mitochondrial or bacterial respiratory electron transport chain, which utilize a unique heterobinuclear active site to catalyze the 4H+/4e– ...reduction of dioxygen to water. This process involves a proton-coupled electron transfer (PCET) from a tyrosine (phenolic) residue and additional redox events coupled to transmembrane proton pumping and ATP synthesis. Given that HCOs are large, complex, membrane-bound enzymes, bioinspired synthetic model chemistry is a promising approach to better understand heme–Cu-mediated dioxygen reduction, including the details of proton and electron movements. This review encompasses important aspects of heme–O2 and copper–O2 (bio)chemistries as they relate to the design and interpretation of small molecule model systems and provides perspectives from fundamental coordination chemistry, which can be applied to the understanding of HCO activity. We focus on recent advancements from studies of heme–Cu models, evaluating experimental and computational results, which highlight important fundamental structure–function relationships. Finally, we provide an outlook for future potential contributions from synthetic inorganic chemistry and discuss their implications with relevance to biological O2-reduction.
Whether the goal is building a local park or developing disaster response models, collaborative governance is changing the way public agencies at the local, regional, and national levels are working ...with each other and with key partners in the nonprofit and private sectors. While the academic literature has spawned numerous case studies and context- or policy-specific models for collaboration, the growth of these innovative collaborative governance systems has outpaced the scholarship needed to define it.Collaborative Governance Regimesbreaks new conceptual and practical ground by presenting an integrative framework for working across boundaries to solve shared problems, a typology for understanding variations among collaborative governance regimes, and an approach for assessing both process and productivity performance. This book draws on diverse literatures and uses rich case illustrations to inform scholars and practitioners about collaborative governance regimes and to provide guidance for designing, managing, and studying such endeavors in the future.Collaborative Governance Regimeswill be of special interest to scholars and researchers in public administration, public policy, and political science who want a framework for theory building, yet the book is also accessible enough for students and practitioners.
Metallodrugs offer potential for unique mechanism of drug action based on the choice of the metal, its oxidation state, the types and number of coordinated ligands and the coordination geometry. This ...review illustrates notable recent progress in the field of medicinal bioinorganic chemistry as many new approaches to the design of innovative metal-based anticancer drugs are emerging. Current research addressing the problems associated with platinum drugs has focused on other metal-based therapeutics that have different modes of action and on prodrug and targeting strategies in an effort to diminish the side-effects of cisplatin chemotherapy. Examples of metal compounds and chelating agents currently in clinical use, clinical trials or preclinical development are highlighted.
This review gives an overview of the relevant medicinal chemistry of platinum, palladium, gold and ruthenium complexes, which could be used for anticancer or biomedical applications. Display omitted
•Pt complexes that intercalate with DNA typically exhibit anticancer activity.•Pd complexes showed good binding affinity to DNA and proteins.•The thiol–enzymes are considered key molecular targets of anticancer Au complexes.•Ru complexes has been considered to be an attractive alternative to Pt complexes.
Transition metal complexes are of increasing interest as photosensitizers in photodynamic therapy (PDT) and, more recently, for photochemotherapy (PCT). In recent years, Ru(II) polypyridyl complexes ...have emerged as promising systems for both PDT and PCT. Their rich photochemical and photophysical properties derive from a variety of excited-state electronic configurations accessible with visible and near-infrared light, and these properties can be exploited for both energy- and electron-transfer processes that can yield highly potent oxygen-dependent and/or oxygen-independent photobiological activity. Selected examples highlight the use of rational design in coordination chemistry to control the lowest-energy triplet excited-state configurations for eliciting a particular type of photoreactivity for PDT and/or PCT effects. These principles are also discussed in the context of the development of TLD1433, the first Ru(II)-based photosensitizer for PDT to enter a human clinical trial. The design of TLD1433 arose from a tumor-centered approach, as part of a complete PDT package that includes the light component and the protocol for treating non-muscle invasive bladder cancer. Briefly, this review summarizes the challenges to bringing PDT into mainstream cancer therapy. It considers the chemical and photophysical solutions that transition metal complexes offer, and it puts into context the multidisciplinary effort needed to bring a new drug to clinical trial.
Light-emitting supramolecular coordination complexes (SCCs) have been widely studied for applications in the chemical and biological sciences. Herein, we report the coordination-driven self-assembly ...of two highly emissive platinum(II) supramolecular triangles (1 and 2) containing BODIPY-based bridging ligands. The metallacycles exhibit favorable anticancer activities against HeLa cells (IC50 of 6.41 and 2.11 μM). The characteristic ∼570 nm fluorescence of the boron dipyrromethene (BODIPY) moieties in the metallacycles permits their intracellular visualization using confocal microscopy. Additionally, the BODIPY fluorophore is an excellent photodynamic agent, making the metallacycles as ideal therapeutics for photodynamic therapy (PDT) and chemotherapy. In vitro studies demonstrate that the combination indexes against HeLa cells are 0.56 and 0.48 for 1 and 2, respectively, confirming their synergistic anticancer effect. More importantly, these SCCs also exhibit superior anticancer efficacy toward cisplatin-resistant A2780cis cell line by combining PDT and chemotherapy, showing promise in overcoming drug resistance. This study exploits a multicomponent approach to self-assembled metallacages that enables design of effective theranostic agents wherein the platinum acceptors are toxic chemotherapeutics and the BODIPY donors are imaging probes and photosensitizers. Since each piece may be independently tuned, i.e., Pt(II) polypyridyl fragment swapped for Pt(II) phosphine, the activity may be optimized without a total redesign of the system.
The discovery of cisplatin's antitumor activity in 1969 prompted the search for novel metal-containing complexes as potential anticancer drugs. Among these novel complexes, metal N-heterocyclic ...carbene (NHC) complexes have recently gained considerable attention because they perfectly fit prerequisites for efficient drug design and fast optimization. Moreover, most of them have shown higher cytotoxicity than cisplatin. This review describes the advances that have been achieved in using transition metal (Ag, Au, Pt, Pd, Cu, Ni, and Ru) complexes containing NHC ligands as antitumor agents. Their modes of action at the cellular lever are further discussed. All these initial achievements clearly demonstrate the great potential of metal-NHC complexes as antitumor agents.
A different interlimb coordination and higher variability in movement patterns is evident in children with Developmental Coordination Disorder (DCD). The impact of DCD on interlimb coordination ...during walking and running is unknown.
To assess interlimb coordination and spatiotemporal variability during overground walking and running in children with and without DCD.
Children with DCD and typically developing children (TDC), from 8 to 12 years participated. Children were equipped with portable sensors. Participants walked and ran for 3 min in an oval-path at their comfortable pace. Interlimb coordination, expressed by the phase coordination index (PCI), and spatiotemporal variability (coefficient of variance (CoV)) were collected.
Twenty-one children with DCD and 23 TDC participated. During walking, PCI showed similar values in both groups, but a higher spatiotemporal variability was observed in children with DCD. During running, PCI was higher (reduced coordination) in children with DCD than TDC and a higher spatiotemporal variability was shown.
Only during running, interlimb coordination of children with DCD was lower than TDC. During both walking and running tasks, spatiotemporal variability was higher in DCD. Current results implicate that difficulties in children with DCD is more prominent when motor coordination is more challenged.
This paper adds to the literature on coordination and gait pattern in children with Developmental Coordination Disorder (DCD) through a cross-sectional analysis of interlimb coordination and variability of spatiotemporal measures of overground walking and running. Overground walking and running were performed in a large oval-path allowing the assessment of coordination and gait patterns in an ecological valid set-up. Our results indicate that during a more demanding task, namely running, children with DCD display a less coordinated running pattern, expressed by a significantly higher phase coordination index, than typically developing peers. During walking, the interlimb coordination was similar between both groups. The current result is in accordance with the hybrid model of DCD that states that motor coordination difficulties in DCD are dpendent on the interaction of the task, individual and environment. This highlights the importance of implementing running assessments in children with DCD and the need for task-oriented running training in clinical practice The study also supports previous findings that children with DCD show a higher variability in their gait pattern of both walking and running, expressed by higher coefficient of variance of spatiotemporal measures, than typically developing peers. Further understanding in the normal development of interlimb coordination during walking and running from childhood into adulthood will enhance interpretations of the phase coordination index in children with and without DCD.
•Children with DCD have a lower interlimb coordination than TDC during running.•During walking, interlimb coordination does not significantly differ between groups.•During walking and running: spatiotemporal variability is higher in DCD than TDC.•Spatiotemporal measures differ between groups during running but not during walking.
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