Inducing social self‐sorting in organic cages to tune the shape of the internal cavity

Many interesting target guest molecules have low symmetry, yet most methods for synthesising hosts result in highly symmetrical capsules. Methods of generating lower symmetry pores are thus required to maximise the binding affinity in host–guest complexes. Herein, we use mixtures of tetraaldehyde building blocks with cyclohexanediamine to access low-symmetry imine cages. Whether a low-energy cage is isolated can be correctly predicted from the thermodynamic preference observed in computational models. The stability of the observed structures depends on the geometrical match of the aldehyde building blocks. One bent aldehyde stands out as unable to assemble into high-symmetry cages-and the same aldehyde generates low-symmetry socially self-sorted cages when combined with a linear aldehyde. We exploit this finding to synthesise a family of low-symmetry cages containing heteroatoms, illustrating that pores of varying geometries and surface chemistries may be reliably accessed through computational prediction and self-sorting

Biochemical aspects of nitric oxide synthase feedback regulation by nitric oxide

Nitric oxide (NO) is a small gas molecule derived from at least three isoforms of the enzyme termed nitric oxide synthase (NOS). More than 15 years ago, the question of feedback regulation of NOS activity and expression by its own product was raised. Since then, a number of trials have verified the existence of negative feedback loop both in vitro and in vivo. NO, whether released from exogenous donors or applied in authentic NO solution, is able to inhibit NOS activity and also intervenes in NOS expression processes by its effect on transcriptional nuclear factor NF-κB. The existence of negative feedback regulation of NOS may provide a powerful tool for experimental and clinical use, especially in inflammation, when massive NOS expression may be detrimental

Harnessing collective intelligence for the future of learning – a co-constructed research and development agenda

Learning, defined as the process of constructing meaning and developing competencies to act on it, is instrumental in helping individuals, communities, and organizations tackle challenges. When these challenges increase in complexity and require domain knowledge from diverse areas of expertise, it becomes difficult for single individuals to address them. In this context, collective intelligence, a capacity of groups of people to act together and solve problems using their collective knowledge, becomes of great importance. Technologies are instrumental both to support and understand learning and collective intelligence, hence the need for innovations in the area of technologies that can support user needs to learn and tackle collective challenges. Use-inspired research is a fitting paradigm that spans applied solutions and scientific explanations of the processes of learning and collective intelligence, and that can improve the technologies that may support them. Although some conceptual and theoretical work explaining and linking learning with collective intelligence is emerging, technological infrastructures as well as methodologies that employ and evidence that support them are nascent. We convened a group of experts to create a middleground and engage with the priorities for use-inspired research. Here we detail directions and methods they put forward as most promising for advancing a scientific agenda around learning and collective intelligence

Health Technology Assessment: a value-based tool for the evaluation of healthcare technologies. Reassessment of the cell-culture-derived quadrivalent influenza vaccine: Flucelvax Tetra® 2.0

1. Health Technology Assessment: strumento value‑based per la valutazione delle tecnologie sanitarie 2. Il burden dell'influenza stagionale in Italia 3. Epidemiologia dell’influenza stagionale in Italia 4. Vaccini antinfluenzali attualmente disponibili in Italia 5. Flucelvax Tetra®, il vaccino quadrivalente su coltura cellulare: una revisione sistematica e meta-analisi di immunogenicità, efficacia e sicurezza 6. Valutazione economica dell’introduzione del nuovo vaccino antinfluenzale quadrivalente da coltura cellulare nel contesto di cura italiano (update da nuova indicazione) 7. Aspetti organizzativi della vaccinazione antinfluenzale in Italia 8. Valutazione etica dell'introduzione del vaccino antinfluenzale quadrivalente da coltura cellulare 9. Il valore della vaccinazione antinfluenzale nel quadro più complesso della Value-Based Healthcare 10. Elelemnti chiave per il processo decisional

Ecosemiotics: A new field of competence for ecology to overcome the frontier between environmental complexity and human culture in the Mediterranean

The Mediterranean region shows unique environmental and ecological characteristics. The observed ecological complexity is the result of a long-lasting and intense co-evolutionary process between human and non-human organisms. Most of the valuable landscapes at the present time are under serious threat from agricultural intensification, land abandonment and forestation, urban sprawl, and mass tourism. The urgency of conservation clashes against these threats. Such complexity of human–nature interactions is best represented by the “full and empty” world ecological model. Cultural landscape and niche construction theories belong to this framework. In turn, perception and cognition are central themes in the definition of such paradigms. This leads ecological research into the field of eco-semiotics, a new scientific perspective that can provide powerful tools for the study of the Mediterranean ecological complexity, as it addresses the interpretation of signs that human and other evolutionary drivers leave in the environment. Such signs are the expression of mutual interactions that shaped patterns and processes in the region. The eco-field paradigm, derived from the eco-semiotic approach, is a theoretical tool that allows one to intercept a portion of such signals to model the relationship between any species and its environment

Targeting metabotropic glutamate receptors in the treatment of epilepsy: Rationale and current status

Introduction: Several drugs targeting the GABAergic system are used in the treatment of epilepsy, but only one drug targeting glutamate receptors is on the market. This is surprising because an imbalance between excitatory and inhibitory neurotransmission lies at the core of the pathophysiology of epilepsy. One possible explanation is that drug development has been directed towards the synthesis of molecules that inhibit the activity of ionotropic glutamate receptors. These receptors mediate fast excitatory synaptic transmission in the central nervous system (CNS) and their blockade may cause severe adverse effects such as sedation, cognitive impairment and psychotomimetic effects. Metabotropic glutamate (mGlu) receptors are more promising drug targets because these receptors modulate synaptic transmission rather than mediate it. Areas covered: We review the current evidence that links mGlu receptor subtypes to the pathophysiology and experimental treatment of convulsive and absence seizures. Expert Opinion: While mGlu5 receptor negative allosteric modulators have the potential to be protective against convulsive seizures and hyperactivity-induced neurodegeneration, drugs that enhance mGlu5 and mGlu7 receptor function may have beneficial effects in the treatment of absence epilepsy. Evidence related to the other mGlu receptor subtypes is more fragmentary; further investigations are required for an improved understanding of their role in the generation and propagation of seizures

Metabotropic glutamate receptors in the thalamocortical network: Strategic targets for the treatment of absence epilepsy

Metabotropic glutamate (mGlu) receptors are positioned at synapses of the thalamocortical network that underlie the development of spike-and-wave discharges (SWDs) associated with absence epilepsy. The modulatory role of individual mGlu receptor subtypes on excitatory and inhibitory synaptic transmission in the cortico-thalamo-cortical circuitry makes subtype-selective mGlu receptor ligands potential candidates as novel antiabsence drugs. Some of these compounds are under clinical development for the treatment of numerous neurologic and psychiatric disorders, and might be soon available for clinical studies in patients with absence seizures refractory to conventional medications. Herein we review the growing evidence that links mGlu receptors to the pathophysiology of pathologic SWDs moving from the anatomic localization and function of distinct mGlu receptor subtypes in the cortico-thalamo-cortical network to in vivo studies in mouse and rat models of absence epilepsy. © 2011 International League Against Epilepsy