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In criminal law jurisprudence, punishment of an offender is usually secured after conviction following a successful prosecution based on evidence. The conviction of an offender can be secured by evidence from a single witness with or without corroborated. In Nigeria, evidence on issues of carnal knowledge, capacity, consent, corroboration and limitation period remain challenging in securing conviction of an offender in sexual offences. This work examines the challenging issues on sexual offences in Nigerian criminal law jurisprudence. The work made use of the doctrinal methodology and found that: (i) having canal knowledge of the victim is sacrosanct in securing the conviction of an offender in sexual offence cases; (ii) there is absence of a provision on the age limits at which a female offender maybe held incapable of committing sexual offence; (iii) absent of consent before penetration is very germane in cases of sexual offence; (iv) the law requires evidence of corroboration in only specific named sexual offences for conviction of an offender; and (v) there is a time limit within which an offender can be prosecuted for committing sexual offence. Accordingly this work recommends that a provision on age limits at which a female offender maybe held incapable of committing sexual offence should be expressly provided in the law; the court should not insist on evidence of corroboration in sexual offences where such evidence is not required by law; and, the limitation of time for prosecution of offenders of sexual offences should be expunged from the Criminal Code Act and or any other law. Keywords: Corroboration, Contending Issues, Criminal Law, Sexual Offences, Jurisprudence. Title: An Examination of Challenging Issues on Sexual Offences in Nigerian Criminal Law Jurisprudence Author: Dr. Michael D. Hanson International Journal of Recent Research in Social Sciences and Humanities (IJRRSSH) ISSN 2349-7831 Vol. 10, Issue 2, April 2023 - June 2023 Page No: 140-149 Paper Publications Website: www.paperpublications.org Published Date: 29-June-2023 DOI: https://doi.org/10.5281/zenodo.8093975 Paper Download Link (Source) https://www.paperpublications.org/upload/book/An%20Examination%20of%20Challenging%20Issues-29062023-1.pdf, International Journal of Recent Research in Social Sciences and Humanities (IJRRSSH), ISSN 2349-7831, Paper Publications, Website: www.paperpublications.org

Acts of terrorism in Nigeria have been identified with different terrorist groups, particularly, Boko Haram. This group emerged, developed and carried out several attacks in Nigeria from 2009 till date. During the commencement of hostilities, their targets were mostly restricted to the security officials in addition to civilians, their communities and business establishments. Later, their targets were expanded and nothing was spared. Their activities resulted in huge destruction of lives and property as well as displacement of millions of people. This work appraises the impact of Boko Haram terrorism on national security and national development in Nigeria. Using the doctrinal methodology, this work finds that acts of terrorism perpetrated by Boko Haram have seriously weakened national security and crippled national development advancement in Nigeria. Accordingly, this work recommends strengthening of national security and addressing the ill indicators of development, particularly, education, poverty, unemployment and persistent injustice in the country.

The technique of cryogenic-electron microscopy (cryo-EM) has revolutionized the field of membrane protein structure and function with a focus on the dominantly observed molecular species. This report describes the structural characterization of a fully active human apelin receptor (APJR) complexed with heterotrimeric G protein observed in both 2:1 and 1:1 stoichiometric ratios. We use cryo-EM single-particle analysis to determine the structural details of both species from the same sample preparation. Protein preparations, in the presence of the endogenous peptide ligand ELA or a synthetic small molecule, both demonstrate these mixed stoichiometric states. Structural differences in G protein engagement between dimeric and monomeric APJR suggest a role for the stoichiometry of G protein-coupled receptor- (GPCR-)G protein coupling on downstream signaling and receptor pharmacology. Furthermore, a small, hydrophobic dimer interface provides a starting framework for additional class A GPCR dimerization studies. Together, these findings uncover a mechanism of versatile regulation through oligomerization by which GPCRs can modulate their signaling.

What can science and science fiction tell us about the intertwining of the actual and the possible, the relations of imagination and reality? What are some of the ways those relationships can work? Should we be foregrounding possibilities that come primarily from our imaginations or the realities that push our imaginations? Contrary to common assumptions, this essay argues that imagination itself tends to be quite limited, but in some situations can become dangerously ungrounded. In contrast, the challenges of reality are more likely to push us to imagine previously inconceivable and transformative possibilities.

We present the design of ATJ graphite [1] rods developed for ablation experiments under high heat flux (up to 50 MW/m2) in the lower divertor of the DIII-D tokamak [2], a magnetic plasma confinement device. This work is motivated by the need to test ablation models relevant to carbon-based thermal shields used in high-speed spacecraft atmospheric entries, where the heat fluxes encountered can be comparable to those achieved in the DIII-D divertor plasma. Several different designs for the flow-facing side of the rod are analyzed, including “sharp nose,” “blunt,” and “concave”. The last shape is studied for its potential to lower heat fluxes at the rod surface by increased radiation from trapped neutrals and reduced parallel plasma pressure. We also analyze the possibility of applying a thin (approximately 30 microns) layer of silicon carbide (SiC) to the exposed part of several carbon ablation rods to benchmark its erosion calculations and lifetime predictions. Such calculations are of interest as SiC represents a promising material for both thermal protection systems (TPS) and a fusion plasma-facing material (PFM). [3,4] Preliminary results from the DIII-D rod ablation experiments are also discussed.

Este manifiesto, discutido por 20 académicos y académicas que representan diversas líneas de investigación sobre la creatividad, marca un cambio conceptual dentro de los estudios de este campo. Los enfoques socioculturales han hecho contribuciones sustanciales al concepto de creatividad en las últimas décadas y hoy pueden proporcionar un conjunto de propuestas para guiar nuestra comprensión de la investigación anterior y generar nuevas direcciones en investigación y práctica. Estas proposiciones son urgentemente necesarias en respuesta a la transición de una Sociedad de la Información a una Sociedad Post-Información. A través de las proposiciones descritas aquí, nuestro objetivo es construir un terreno común e invitar a la comunidad de investigadores y profesionales de la creatividad a reflexionar, estudiar y cultivar la creatividad como un fenómeno sociocultural.

This manifesto, discussed by 20 scholars, representing diverse lines of creativity research, marks a conceptual shift within the field. Socio-cultural approaches have made substantial contributions to the concept of creativity over recent decades and today can provide a set of propositions to guide our understanding of past research and to generate new directions of inquiry and practice. These propositions are urgently needed in response to the transition from the Information Society to the Post-Information Society. Through the propositions outlined here, we aim to build common ground and invite the community of creativity researchers and practitioners to reflect up, study, and cultivate creativity as a socio-cultural phenomenon.

Howard Gruber was an activist, developmental psychologist, and educator. His life left a rich legacy, especially his view of creativity, a systems perspective on the individual as a force of change. Gruber was inspired by two conflicting views of social change. The first: historical materialism with its analysis of complex and powerful social, economic, and historical forces. The second: individual agency as necessary for human morality. His work with Piaget and his own extensive research on Charles Darwin were part of a quest to understand how individuals can have social impact, given the constraints of social forces and historical context. The purpose of this paper is to consider the educational implications of Gruber’s understanding of creative agency. The first part of the paper analyzes the development of Gruber’s own point of view through scholarship and activism. The second part analyzes Gruber’s evolving systems approach to the creative development of the individual within socio-historical contexts, including current elaborations of Gruber’s work—distributed and participatory views of creativity. The third discusses implications of these views for education. Lifespan developmental, holistic, and distributed views of creativity differ markedly from older ideation-focused approaches in how they support the education of students as active participants in their worlds.

Glucagon-like peptide-1 receptor (GLP-1R) is a class B G protein-coupled receptor that plays an important role in glucose homeostasis and treatment of type 2 diabetes. Structures of full-length class B receptors were determined in complex with their orthosteric agonist peptides, however, little is known about their extracellular domain (ECD) conformations in the absence of orthosteric ligands, which has limited our understanding of their activation mechanism. Here, we report the 3.2 Å resolution, peptide-free crystal structure of the full-length human GLP-1R in an inactive state, which reveals a unique closed conformation of the ECD. Disulfide cross-linking validates the physiological relevance of the closed conformation, while electron microscopy (EM) and molecular dynamic (MD) simulations suggest a large degree of conformational dynamics of ECD that is necessary for binding GLP-1. Our inactive structure represents a snapshot of the peptide-free GLP-1R and provides insights into the activation pathway of this receptor family., Glucagon-like peptide-1 receptor (GLP-1R) plays an important role in glucose homeostasis and treatment of type 2 diabetes. Here authors report the peptide-free crystal structure of human GLP-1R in an inactive state which reveals a unique closed conformation of the extracellular domain.

G protein-coupled receptors (GPCRs) represent the largest class of cell surface proteins and thus constitute an important family of therapeutic targets. Therefore, significant effort has been put towards the identification of novel ligands that can modulate the activity of a GPCR target with high efficacy and selectivity. However, due to limitations inherent to the most common techniques for GPCR ligand discovery, there is a pressing need for more efficient and effective ligand screening methods especially for the identification of potential allosteric modulators. Here we present a high-throughput, label-free and unbiased screening approach for the identification of small molecule ligands towards GPCR targets based on affinity mass spectrometry. This new approach features the usage of target-expressing cell membranes rather than purified proteins for ligand screening and allows the detection of both orthosteric and allosteric ligands targeting specific GPCRs. Screening a small compound library with this approach led to the rapid discovery of an antagonist for the 5-HT receptor and four positive allosteric modulators for GLP-1 receptor that were not previously reported.

Crystal structures of the human cannabinoid receptor 1 (CB1) bound to the agonists AM11542 and AM841 reveal notable structural rearrangements upon receptor activation, and this flexibility may be a common feature among other G-protein-coupled receptors. The human cannabinoid receptor 1 (CB1) is the main target of the plant cannabinoid Δ9-tetrahydrocannbinol (Δ9-THC), the key psychoactive compound in Cannabis sativa. CB1 is activated by endocannabinoids and is a therapeutic target for pain management, epilepsy and obesity, among others, although an active receptor structure is still lacking. Here, Zhi-Jie Liu and colleagues report the crystal structure of CB1 activated by two potent Δ9-THC derivatives, AM11542 and AM841. Both of these agonists have a gem-dimethyl group on their alkyl chain which leads to significant enhancement in their potency and efficacy. Receptor activation involves large-scale structural rearrangements on both extracellular and cytoplasmic sides and a significant reduction in the size of the binding pocket. These conformational changes involve a novel molecular 'twin toggle switch', the synergistic movement of two key residues during activation, which the authors suggest may be common to other G-protein-coupled receptors. The cannabinoid receptor 1 (CB1) is the principal target of the psychoactive constituent of marijuana, the partial agonist Δ9-tetrahydrocannabinol (Δ9-THC)1. Here we report two agonist-bound crystal structures of human CB1 in complex with a tetrahydrocannabinol (AM11542) and a hexahydrocannabinol (AM841) at 2.80 A and 2.95 A resolution, respectively. The two CB1–agonist complexes reveal important conformational changes in the overall structure, relative to the antagonist-bound state2, including a 53% reduction in the volume of the ligand-binding pocket and an increase in the surface area of the G-protein-binding region. In addition, a ‘twin toggle switch’ of Phe2003.36 and Trp3566.48 (superscripts denote Ballesteros–Weinstein numbering3) is experimentally observed and appears to be essential for receptor activation. The structures reveal important insights into the activation mechanism of CB1 and provide a molecular basis for predicting the binding modes of Δ9-THC, and endogenous and synthetic cannabinoids. The plasticity of the binding pocket of CB1 seems to be a common feature among certain class A G-protein-coupled receptors. These findings should inspire the design of chemically diverse ligands with distinct pharmacological properties.

The human glucagon receptor, GCGR, belongs to the class B G-protein-coupled receptor family and plays a key role in glucose homeostasis and the pathophysiology of type 2 diabetes. Here we report the 3.0 Å crystal structure of full-length GCGR containing both the extracellular domain and transmembrane domain in an inactive conformation. The two domains are connected by a 12-residue segment termed the stalk, which adopts a β-strand conformation, instead of forming an α-helix as observed in the previously solved structure of the GCGR transmembrane domain. The first extracellular loop exhibits a β-hairpin conformation and interacts with the stalk to form a compact β-sheet structure. Hydrogen-deuterium exchange, disulfide crosslinking and molecular dynamics studies suggest that the stalk and the first extracellular loop have critical roles in modulating peptide ligand binding and receptor activation. These insights into the full-length GCGR structure deepen our understanding of the signalling mechanisms of class B G-protein-coupled receptors.

Crystal structures provide first atomic-level insights into δ-opioid receptor activation by two structurally diverse agonists., Selective activation of the δ-opioid receptor (DOP) has great potential for the treatment of chronic pain, benefitting from ancillary anxiolytic and antidepressant-like effects. Moreover, DOP agonists show reduced adverse effects as compared to μ-opioid receptor (MOP) agonists that are in the spotlight of the current “opioid crisis.” Here, we report the first crystal structures of the DOP in an activated state, in complex with two relevant and structurally diverse agonists: the potent opioid agonist peptide KGCHM07 and the small-molecule agonist DPI-287 at 2.8 and 3.3 Å resolution, respectively. Our study identifies key determinants for agonist recognition, receptor activation, and DOP selectivity, revealing crucial differences between both agonist scaffolds. Our findings provide the first investigation into atomic-scale agonist binding at the DOP, supported by site-directed mutagenesis and pharmacological characterization. These structures will underpin the future structure-based development of DOP agonists for an improved pain treatment with fewer adverse effects.

A growing number of scholars have come to see creativity, not as a trait or force or process, but as ideology – a set of seldom questioned values and assumptions about individuals and change that characterizes our time while unifying and reinforcing other ideological concepts, such as individualism and neophilia. What does this ideology look like in education? Can educators manage its impact, and even influence its meaning? In other words, inevitably working from within our ideology of creativity, what moves are available once we are aware of the stakes?

This chapter introduces the concept of participatory creativity as a dynamic approach to invention and innovation that is particularly relevant to the field of education. Here, the focus of creativity studies shifts from individual ideation to interactions within complex sociohistorical systems. While acknowledging the roles played by those who successfully commit exceptional energy and resources to creative projects and new points of view, the participatory approach reframes those previously deemed as creative individuals as participants in larger narratives. These complex processes of change are described as the biographies of ideas. People play various roles as they contribute to these biographies over time. Such roles are social positions that are neither fixed nor uni-dimensional, but dynamic. After framing this position from a theoretical perspective, the authors offer two examples of participatory creativity in action. These examples show how moving the locus of creativity from individual ideation to social participation makes visible the many ways that young people can participate in the development of creative ideas, while also establishing their own unique “profile of participation” and encouraging creative agency—all while honoring students’ diverse knowledge, expertise, background experiences, and sociocultural perspectives. After discussing some of the limitations of this reframing of creativity as a participatory process, the authors conclude by suggesting implications for practice and future research.

The glucagon-like peptide-1 receptor (GLP-1R) belongs to the secretin-like (class B) family of G protein-coupled receptors. Members of the class B family are distinguished by their large extracellular domain, which works cooperatively with the canonical seven-transmembrane (7TM) helical domain to signal in response to binding of various peptide hormones. We have combined structure-based site-specific mutational studies with molecular dynamics simulations of a full-length model of GLP-1R bound to multiple peptide ligand variants. Despite the high sequence similarity between GLP-1R and its closest structural homologue, the glucagon receptor (GCGR), nearly half of the 62 stably expressed mutants affected GLP-1R in a different manner than the corresponding mutants in GCGR. The molecular dynamics simulations of wild-type and mutant GLP-1R·ligand complexes provided molecular insights into GLP-1R-specific recognition mechanisms for the N terminus of GLP-1 by residues in the 7TM pocket and explained how glucagon-mimicking GLP-1 mutants restored binding affinity for (GCGR-mimicking) GLP-1R mutants. Structural analysis of the simulations suggested that peptide ligand binding mode variations in the 7TM binding pocket are facilitated by movement of the extracellular domain relative to the 7TM bundle. These differences in binding modes may account for the pharmacological differences between GLP-1 peptide variants.

Misoprostol is a life-saving drug in many developing countries for women at risk of post-partum hemorrhaging owing to its affordability, stability, ease of administration and clinical efficacy. However, misoprostol lacks receptor and tissue selectivities, and thus its use is accompanied by a number of serious side effects. The development of pharmacological agents combining the advantages of misoprostol with improved selectivity is hindered by the absence of atomic details of misoprostol action in labor induction. Here, we present the 2.5 A resolution crystal structure of misoprostol free-acid form bound to the myometrium labor-inducing prostaglandin E2 receptor 3 (EP3). The active state structure reveals a completely enclosed binding pocket containing a structured water molecule that coordinates misoprostol's ring structure. Modeling of selective agonists in the EP3 structure reveals rationales for selectivity. These findings will provide the basis for the next generation of uterotonic drugs that will be suitable for administration in low resource settings. A structure of the prostaglandin E2 receptor 3 (EP3) bound to the agonist misoprostol shows a completely enclosed binding pocket with a structured water molecule that coordinates misoprostol's ring structure and explains the receptor's selectivity.

SummaryLipid biology continues to emerge as an area of significant therapeutic interest, particularly as the result of an enhanced understanding of the wealth of signaling molecules with diverse physiological properties. This growth in knowledge is epitomized by lysophosphatidic acid (LPA), which functions through interactions with at least six cognate G protein-coupled receptors. Herein, we present three crystal structures of LPA1 in complex with antagonist tool compounds selected and designed through structural and stability analyses. Structural analysis combined with molecular dynamics identified a basis for ligand access to the LPA1 binding pocket from the extracellular space contrasting with the proposed access for the sphingosine 1-phosphate receptor. Characteristics of the LPA1 binding pocket raise the possibility of promiscuous ligand recognition of phosphorylated endocannabinoids. Cell-based assays confirmed this hypothesis, linking the distinct receptor systems through metabolically related ligands with potential functional and therapeutic implications for treatment of disease.

The crystal structure of the full-length glucagon receptor in complex with a glucagon analogue NNC1702 reveals how the peptide ligand interacts with its target and shows the conformational changes required for receptor activation. The glucagon receptor is a class B G-protein-coupled receptor with an important role in glucose homeostasis. Activation of this receptor triggers the release of glucose, making it an important target for the treatment of type 2 diabetes. Beili Wu and colleagues now report the crystal structure of the full-length glucagon receptor bound to a glucagon analogue and a partial agonist, NNC1702. The 3.0 A resolution of the structure provides key insights into how the peptide ligand interacts with its target and the conformational changes involved in the initial stages of activation. The structural data is reinforced by using double electron–electron resonance (DEER) spectroscopy, which demonstrates the extent of rearrangement that is involved in accommodating the glucagon analogue. Class B G-protein-coupled receptors (GPCRs), which consist of an extracellular domain (ECD) and a transmembrane domain (TMD), respond to secretin peptides to play a key part in hormonal homeostasis, and are important therapeutic targets for a variety of diseases1,2,3,4,5,6,7,8. Previous work9,10,11 has suggested that peptide ligands bind to class B GPCRs according to a two-domain binding model, in which the C-terminal region of the peptide targets the ECD and the N-terminal region of the peptide binds to the TMD binding pocket. Recently, three structures of class B GPCRs in complex with peptide ligands have been solved12,13,14. These structures provide essential insights into peptide ligand recognition by class B GPCRs. However, owing to resolution limitations, the specific molecular interactions for peptide binding to class B GPCRs remain ambiguous. Moreover, these previously solved structures have different ECD conformations relative to the TMD, which introduces questions regarding inter-domain conformational flexibility and the changes required for receptor activation. Here we report the 3.0 A-resolution crystal structure of the full-length human glucagon receptor (GCGR) in complex with a glucagon analogue and partial agonist, NNC1702. This structure provides molecular details of the interactions between GCGR and the peptide ligand. It reveals a marked change in the relative orientation between the ECD and TMD of GCGR compared to the previously solved structure of the inactive GCGR–NNC0640–mAb1 complex. Notably, the stalk region and the first extracellular loop undergo major conformational changes in secondary structure during peptide binding, forming key interactions with the peptide. We further propose a dual-binding-site trigger model for GCGR activation—which requires conformational changes of the stalk, first extracellular loop and TMD—that extends our understanding of the previously established two-domain peptide-binding model of class B GPCRs.

The glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCGR) are members of the secretin-like class B family of G-protein-coupled receptors (GPCRs) and have opposing physiological roles in insulin release and glucose homeostasis. The treatment of type 2 diabetes requires positive modulation of GLP-1R to inhibit glucagon secretion and stimulate insulin secretion in a glucose-dependent manner. Here we report crystal structures of the human GLP-1R transmembrane domain in complex with two different negative allosteric modulators, PF-06372222 and NNC0640, at 2.7 and 3.0 Å resolution, respectively. The structures reveal a common binding pocket for negative allosteric modulators, present in both GLP-1R and GCGR and located outside helices V-VII near the intracellular half of the receptor. The receptor is in an inactive conformation with compounds that restrict movement of the intracellular tip of helix VI, a movement that is generally associated with activation mechanisms in class A GPCRs. Molecular modelling and mutagenesis studies indicate that agonist positive allosteric modulators target the same general region, but in a distinct sub-pocket at the interface between helices V and VI, which may facilitate the formation of an intracellular binding site that enhances G-protein coupling.

The Smoothened receptor (SMO) belongs to the Class Frizzled of the G protein-coupled receptor (GPCR) superfamily, constituting a key component of the Hedgehog signalling pathway. Here we report the crystal structure of the multi-domain human SMO, bound and stabilized by a designed tool ligand TC114, using an X-ray free-electron laser source at 2.9 Å. The structure reveals a precise arrangement of three distinct domains: a seven-transmembrane helices domain (TMD), a hinge domain (HD) and an intact extracellular cysteine-rich domain (CRD). This architecture enables allosteric interactions between the domains that are important for ligand recognition and receptor activation. By combining the structural data, molecular dynamics simulation, and hydrogen-deuterium-exchange analysis, we demonstrate that transmembrane helix VI, extracellular loop 3 and the HD play a central role in transmitting the signal employing a unique GPCR activation mechanism, distinct from other multi-domain GPCRs., Smoothened receptors (SMO) play a key role in the Hedgehog signalling pathway. Here the authors present the structure of a multi-domain human SMO with a rationally designed stabilizing ligand bound in the transmembrane domain of the receptor, and propose a model for SMO activation.

The cannabinoid receptor 1 (CB1) is the principal target of the psychoactive constituent of marijuana, the partial agonist Δ9-tetrahydrocannabinol (Δ9-THC)1. Here we report two agonist-bound crystal structures of human CB1 in complex with a tetrahydrocannabinol (AM11542) and a hexahydrocannabinol (AM841) at 2.80 Å and 2.95 Å resolution, respectively. The two CB1–agonist complexes reveal important conformational changes in the overall structure, relative to the antagonist-bound state2, including a 53% reduction in the volume of the ligand-binding pocket and an increase in the surface area of the G-protein-binding region. In addition, a ‘twin toggle switch’ of Phe2003.36 and Trp3566.48 (superscripts denote Ballesteros–Weinstein numbering3) is experimentally observed and appears to be essential for receptor activation. The structures reveal important insights into the activation mechanism of CB1 and provide a molecular basis for predicting the binding modes of Δ9-THC, and endogenous and synthetic cannabinoids. The plasticity of the binding pocket of CB1 seems to be a common feature among certain class A G-protein-coupled receptors. These findings should inspire the design of chemically diverse ligands with distinct pharmacological properties.

The sphingosine-1-phosphate (S1P) receptor signaling system has biological and medical importance and is the first lipid G protein–coupled receptor (GPCR) structure to be solved to 2.8-Å resolution. S1P binds to five high-affinity GPCRs generating multiple downstream signals that play essential roles in vascular development and endothelial integrity, control of cardiac rhythm, and routine oral treatment of multiple sclerosis. Genetics, chemistry, and now structural biology have advanced this integrated biochemical system. The S1P receptors have a novel N-terminal fold that occludes access to the binding pocket from the extracellular environment as well as orthosteric and bitopic ligands with very different physicochemical properties. S1P receptors and metabolizing enzymes have been deleted, inducibly deleted, and knocked in as tagged or altered receptors in mice. An array of genetic models allows analysis of integrated receptor function in vivo. We can now directly understand causal relationships among protein expression, signal, and control points in physiology and pathology.

The relationship of individuals to groups has been central, and problematic, to the construct of creativity since it emerged in the 19th and early 20th centuries. Psychological research has often used the idea of creativity to differentiate and/or advocate constructs of the individual as creator, but has used a sociocultural criterion— eminence—to assure validity. Researchers and creative practitioners are then caught in a contradiction in psychology’s own terms: using extrinsic outcomes at the level of culture as the starting point to conceptualize individual activities characterized by intrinsic motivation. Even research that focuses on everyday creativity often identifies creativity only through judgment of products. Sociocultural approaches go further, defining creativity as social judgment of individuals’ works. But what does the eminence of relatively few individuals indicate about social questions (changes in discourse and power relations) or about psychological questions (the people in the system)? This article explores an alternative approach, using Foucault’s analysis of the author function, technologies of self and the related technology typology (production, signs, power and self). Comparing Foucault’s analyses to the psychological discourse demonstrates advantages of integrating Foucault’s ideas into the study of creativity. Analyzing the functions of creativity, rather than its ontology or location, provides a unifying framework for the wide array of approaches psychologists have developed. Within that framework individual experiences can be examined in relation to the distorting nature of the author function, needs for production and shifts in power relations, rather than conflated with them.

Summary Structural studies of human G protein-coupled receptors (GPCRs) have recently been accelerated through the use of a fusion partner that was inserted into the third intracellular loop. Using chimeras of the human β 2 -adrenergic and human A 2A adenosine receptors, we present the methodology and data for the initial selection of an expanded set of fusion partners for crystallizing GPCRs. In particular, use of the thermostabilized apocytochrome b 562 RIL as a fusion partner displays certain advantages over previously utilized fusion proteins, resulting in a significant improvement in stability and structure of GPCR-fusion constructs.

A Lipid-Sensing GPCR Sphingosine 1-phosphate (S1P) is a sphingolipid that binds to the G protein–coupled receptor subtype 1 (S1P 1 ) to activate signaling pathways involved in regulation of the vascular and immune systems. Hanson et al. (p. 851 ) determined the crystal structure of S1PR in complex with an antagonist sphingolipid mimic. Ligand access to the receptor from the extracellular milieu is occluded, and a gap between helices I and VII may provide ligand access from within the membrane. The structural information, together with mutagenesis and structure activity relationship data, provides insight into the molecular recognition events that modulate signaling.