框架描述对医疗资源分配公平感的影响

目的:初步探讨医疗资源分配方案设置及框架描述对人们感知公平的影响。方法:以120名大学生为研究对象,自编情境问题,分别依据Miller定义的平等、需求、责任及付出原则制定医疗资源分配分配方案,采用正、负及平衡框架进行描述。被试被随机分为三组,每组被试需要评估同一框架下,四种分配方案的公平性。结果:结果显示,分配方案主效应显著(F=7.27,P0.01),按照需求原则分配医疗资源,被试感到不公平(t=-2.04,P0.01),而以付出原则分配,被试感到公平(t=2.87,P0.01),以按责与平等原则分配,被试没有显著的公平或不公平感(P.05)。框架描述主效应显著(F=6.08,P.05),以正框架描述,公平感评估显著高于平衡框架与负框架。框架描述与分配原则交互作用显著(F=3.93,P0.01),在正框架下,分配方案效应不显著(F=1.29,P0.05),在负框架与平衡框架下,分配方案效应显著(F平衡=9.23,P0.01;F负=4.69,P0.01)。依据按需与按责原则制定的分配方案受到框架描述影响(F按需=12.88,P0.01;F按责=4.12,P0.05),而依据平等原则、付出原则制定的分配方案不会受到框架描述的影响。结论:分配原则及框架描述均能显著影响人们对医疗资源分配的公平感知。     

Economic Profits Enhance Trust,Perceived Integrity and Memory of Fairness in Interpersonal Judgment

Does money lead to trust in personality and intention of others? Humans have a strong tendency to judge the intention of others from their sequent behaviors. In general, people trust others who behave fairly, but not always. Here we show that judgments of both intentional aspects and memory of intentional behavior are automatically influenced by unintentional benefits from the behaviors of others. We conducted a reward-manipulated and repeated trust game by using real participants interacting with moving image partners on a computer screen. The participants assessed likability, trustworthiness, and perceived integrity of the partners in pre- and post-game questionnaires. The results of judgments of all three dimensions and the memory of frequency of each partner''s fair behavior (sharing) were strongly influenced by profitability in the trust game, even though all partners shared 75% of the profit and participants were told that profitability was randomly assigned to each partner. Furthermore, these effects were moderated by the gender of the participants: males were more sensitive to monetary profits than were females. The results reveal that humans automatically trust, approve the integrity of, and recall well the fair behavior of others who provide affectively positive outcomes such as monetary profits. We call this phenomenon the “affect ripple effect”.     

Belief in a Just World Lowers Perceived Intention of Corruption: The Mediating Role of Perceived Punishment

Corruption can be unfair and detrimental to societies; however, little is known regarding how individuals perceive corruption. We aim to understand how psychological factors, such as lay belief of the world, influence perceived intention of corruptive behavior. As corruption undermines justice, we hypothesize that belief in a just world to others (BJW-others) reduces perceived intention of corruptive behaviors. We conducted two correlational studies and one experimental study in China. Using hypothetical scenarios, perception toward bribery taking and nepotistic practices were assessed. In Study 1 and Study 2, we consistently found that BJW-others negatively predicted perceived intention of corruption, and this pattern was mediated by perceived likelihood of punishment. We further replicate this result in Study 3 by priming BJW-others, demonstrating its causal effect. The results indicate that BJW as one lay belief can be important in influencing people’s attitudes toward corruption. Implications for future research and anti-corruption policies are also discussed.     

Nucleotide Binding to Na,K-ATPase: The Role of Electrostatic Interactions.

The contribution of electrostatic forces to the interaction of Na,K-ATPase with adenine nucleotides was investigated by studying the effect of ionic strength on nucleotide binding. At pH 7.0 and 20 degrees C, there was a qualitative correlation between the equilibrium dissociation constant (K(d)) values for ATP, ADP, and MgADP and their total charges. All K(d) values increased with increasing ionic strength. According to the Debye-Hückel theory, this suggests that the nucleotide binding site and its ligands have "effective" charges of opposite signs. However, quantitative analysis of the dependence on ionic strength shows that the product of the effective electrostatic charges on the ligand and the binding site is the same for all nucleotides, and is therefore independent of the total charge of the nucleotide. The data suggest that association of nucleotides with Na,K-ATPase is governed by a partial charge rather than the total charge of the nucleotide. This charge, interacting with positive charges on the protein, is probably the one corresponding to the alpha-phosphate of the nucleotide. Dissociation rate constants measured in complementary transient kinetic experiments were 13 s(-1) for ATP and 27 s(-1) for ADP, independent of the ionic strength in the range 0.1-0.5 M. This implies similar association rate constants for the two nucleotides (about 40 x 10(6) M(-1) s(-1) at I = 0.1 M). The results suggest that long-range Coulombic forces, affecting association rates, are not the main contributors to the observed differences in affinities, and that local interactions, affecting dissociation rates, may play an even greater role.     

The Role of Solvent Interactions in Protein Conformatio

Abstract

For many years, the ease with which the pH of enzyme reactions could be varied has led to innumerable reports of the pH-dependence of the kinetic parameters of such reactions. These studies have been provided with a veneer of respectability by suggestions that they allow deductions to be made about the nature of the ionizing groups upon which the catalytic activity of the enzyme depends. It is the purpose of this article to summarize some of the reasons why a large proportion of pH-dependence studies yields little information about the real pK_a-values of ionizing groups in enzymes, and still less about the identity of these groups.     

The Role of FilGAP-Filamin A Interactions in Mechanoprotection

Cells in mechanically active environments are subjected to high-amplitude exogenous forces that can lead to cell death. Filamin A (FLNa) may protect cells from mechanically induced death by mechanisms that are not yet defined. We found that mechanical forces applied through integrins enhanced Rac-mediated lamellae formation in FLNa-null but not FLNa-expressing cells. Suppression of force-induced lamella formation was mediated by repeat 23 of FLNa, which also binds FilGAP, a recently discovered Rac GTPase-activating protein (GAP). We found that FilGAP is targeted to sites of force transfer by FLNa. This force-induced redistribution of FilGAP was essential for the suppression of Rac activity and lamellae formation in cells treated with tensile forces. Depletion of FilGAP by small interfering RNA, inhibition of FilGAP activity by dominant-negative mutation or deletion of its FLNa-binding domain, all resulted in a dramatic force-induced increase of the percentage of annexin-V–positive cells. FilGAP therefore plays a role in protecting cells against force-induced apoptosis, and this function is mediated by FLNa.     

The Paradoxical Role of Perceived Control in Late Life Health Behavior

Research has established the health benefits of psychological factors, including the way individuals appraise outcomes. Although many studies confirm that appraising outcomes as controllable is adaptive for health, a paradoxical possibility is largely ignored: Perceived control may be detrimental under some conditions. Our premise was that appraising health as controllable but at the same time ascribing little value to it might signal a dysfunctional psychological mindset that fosters a mistaken sense of invincibility. During face-to-face interviews with a representative sample of older adults (age range = 72–99), we identified individuals with such a potentially maladaptive “invincible” mindset (high perceived control and low health value) and compared them to their counterparts on several outcomes. The findings were consistent with our hypotheses. The invincibles denied future risks, they lacked the activating emotion of fear, and they visited their physicians less often over a subsequent five-year period. Moreover, in contrast to their counterparts, the invincibles did not appear strategic in their approach to seeking care: Even poor health did not prompt them to seek the counsel of a physician. The recognition that psychological appraisals are modifiable highlights the promise of remedial methods to alter maladaptive mindsets, potentially improving quality of life.     

Cooperative Interactions of the Gene 5 Protein

Abstract

Using the refined molecular structure of the Gene 5 DNA Binding Protein (G5BP) and the mechanism of DNA binding deduced from a variety of experimental techniques (G. D. Brayer and A. McPherson, J. Mol. Biol. 169, 565, 1983; G. D. Brayer and A. McPherson, Biochemistry 23, 340, 1984), we have modeled the contiguous, linear aggregation of G5BP dimers along two opposing single strands of DNA. Using both automated graphics systems and systematic calculations of intermolecular contacts between adjacent units, we have optimized the fit of complementary protein surfaces in the presence of DNA. We propose that a minor conformational change involving residues 38–43, triggered by the binding of nucleic acid, relieves several critical steric contacts and permits otherwise extensively complementary surfaces to form an interface. The bonding between surfaces on adjacent G5BP units is the primary source of the cooperativity of binding observed for G5BP. The interacting amino acid residues at the interface are described.     

Protein-Protein Interactions: Principles,Techniques, and their Potential Role in New Drug Development

Abstract

A vast network of genes is inter-linked through protein-protein interactions and is critical component of almost every biological process under physiological conditions. Any disruption of the biologically essential network leads to pathological conditions resulting into related diseases. Therefore, proper understanding of biological functions warrants a comprehensive knowledge of protein-protein interactions and the molecular mechanisms that govern such processes. The importance of protein-protein interaction process is highlighted by the fact that a number of powerful techniques/methods have been developed to understand how such interactions take place under various physiological and pathological conditions. Many of the key protein-protein interactions are known to participate in disease-associated signaling pathways, and represent novel targets for therapeutic intervention. Thus, controlling protein-protein interactions offers a rich dividend for the discovery of new drug targets. Availability of various tools to study and the knowledge of human genome have put us in a unique position to understand highly complex biological network, and the mechanisms involved therein. In this review article, we have summarized protein-protein interaction networks, techniques/methods of their binding/kinetic parameters, and the role of these interactions in the development of potential tools for drug designing.     

Cooperative Aspects of Small Ion, Small Molecule Interactions with Nucleic Acids: Potassium-Polyriboadenylic Acid, Polyribouridylic Acid

Ionic conductivity measurements vs. temperature were made on KCl solutions of K-polyriboadenylic acid + K-polyribouridylic acid (K-poly-A + K-poly-U) in regions of temperature and composition where the helix-coil transition occurred. It was possible to relate the measurements to a differential helix-to-coil binding of K⁺ to nucleotide. The results were, within experimental error, the same as those obtained from a limited number of differential KCl activity coefficient measurements and from a theoretical interpretation of polymer free-boundary electrophoretic mobilities. It was concluded that the alkali ion-phosphate interaction in polynucleotides must be regarded as cooperative in nature and several criteria for recognition of such phenomena were given. A brief outline for a proposed statistical mechanical model for binding was presented.     

Mutational Analysis of Preamyloid Intermediates: The Role of His-Tyr Interactions in Islet Amyloid Formation

Islet amyloid polypeptide (IAPP or Amylin) is a 37-residue, C-terminally amidated pancreatic hormone, cosecreted with insulin that forms islet amyloid in type 2 diabetes. Islet amyloid formation is complex and characterizing preamyloid oligomers is an important topic because oligomeric intermediates are postulated to be the most toxic species produced during fibril formation. A range of competing models for early oligomers have been proposed. The role of the amidated C-terminus in amyloid formation by IAPP and in stabilizing oligomers is not known. Studies with unamidated IAPP have provided evidence for formation of an antiparallel dimer at pH 5.5, stabilized by stacking of His-18 and Tyr-37, but it is not known if this interaction is formed in the physiological form of the peptide. Analysis of a set of variants with a free and with an amidated C-terminus shows that disrupting the putative His-Tyr interaction accelerates amyloid formation, indicating that it is not essential. Amidation to generate the physiologically relevant form of IAPP accelerates amyloid formation, demonstrating that the advantages conferred by C-terminal amidation outweigh increased amyloidogenicity. The analysis of this variant argues that IAPP is not under strong evolutionary pressure to reduce amyloidogenicity. Analysis of an H18Q mutant of IAPP shows that the charge state of the N-terminus is an important factor controlling the rate of amyloid formation, even though the N-terminal region of IAPP is believed to be flexible in the amyloid fibers.     

The Role of Protein Interactions in Mediating Essentiality and Synthetic Lethality

Genes are characterized as essential if their knockout is associated with a lethal phenotype, and these “essential genes” play a central role in biological function. In addition, some genes are only essential when deleted in pairs, a phenomenon known as synthetic lethality. Here we consider genes displaying synthetic lethality as “essential pairs” of genes, and analyze the properties of yeast essential genes and synthetic lethal pairs together. As gene duplication initially produces an identical pair or sets of genes, it is often invoked as an explanation for synthetic lethality. However, we find that duplication explains only a minority of cases of synthetic lethality. Similarly, disruption of metabolic pathways leads to relatively few examples of synthetic lethality. By contrast, the vast majority of synthetic lethal gene pairs code for proteins with related functions that share interaction partners. We also find that essential genes and synthetic lethal pairs cluster in the protein-protein interaction network. These results suggest that synthetic lethality is strongly dependent on the formation of protein-protein interactions. Compensation by duplicates does not usually occur mainly because the genes involved are recent duplicates, but is more commonly due to functional similarity that permits preservation of essential protein complexes. This unified view, combining genes that are individually essential with those that form essential pairs, suggests that essentiality is a feature of physical interactions between proteins protein-protein interactions, rather than being inherent in gene and protein products themselves.     

Mutational Analysis of Preamyloid Intermediates: The Role of His-Tyr Interactions in Islet Amyloid Formation

Islet amyloid polypeptide (IAPP or Amylin) is a 37-residue, C-terminally amidated pancreatic hormone, cosecreted with insulin that forms islet amyloid in type 2 diabetes. Islet amyloid formation is complex and characterizing preamyloid oligomers is an important topic because oligomeric intermediates are postulated to be the most toxic species produced during fibril formation. A range of competing models for early oligomers have been proposed. The role of the amidated C-terminus in amyloid formation by IAPP and in stabilizing oligomers is not known. Studies with unamidated IAPP have provided evidence for formation of an antiparallel dimer at pH 5.5, stabilized by stacking of His-18 and Tyr-37, but it is not known if this interaction is formed in the physiological form of the peptide. Analysis of a set of variants with a free and with an amidated C-terminus shows that disrupting the putative His-Tyr interaction accelerates amyloid formation, indicating that it is not essential. Amidation to generate the physiologically relevant form of IAPP accelerates amyloid formation, demonstrating that the advantages conferred by C-terminal amidation outweigh increased amyloidogenicity. The analysis of this variant argues that IAPP is not under strong evolutionary pressure to reduce amyloidogenicity. Analysis of an H18Q mutant of IAPP shows that the charge state of the N-terminus is an important factor controlling the rate of amyloid formation, even though the N-terminal region of IAPP is believed to be flexible in the amyloid fibers.     

The Unique Kinetics of Iron Release from Transferrin: The Role of Receptor, Lobe-Lobe Interactions, and Salt at Endosomal pH

Transferrins are a family of bilobal iron-binding proteins that play the crucial role of binding ferric iron and keeping it in solution, thereby controlling the levels of this important metal. Human serum transferrin (hTF) carries one iron in each of two similar lobes. Understanding the detailed mechanism of iron release from each lobe of hTF during receptor-mediated endocytosis has been extremely challenging because of the active participation of the transferrin receptor (TFR), salt, a chelator, lobe-lobe interactions, and the low pH within the endosome. Our use of authentic monoferric hTF (unable to bind iron in one lobe) or diferric hTF (with iron locked in one lobe) provided distinct kinetic end points, allowing us to bypass many of the previous difficulties. The capture and unambiguous assignment of all kinetic events associated with iron release by stopped-flow spectrofluorimetry, in the presence and in the absence of the TFR, unequivocally establish the decisive role of the TFR in promoting efficient and balanced iron release from both lobes of hTF during one endocytic cycle. For the first time, the four microscopic rate constants required to accurately describe the kinetics of iron removal are reported for hTF with and without the TFR. Specifically, at pH 5.6, the TFR enhances the rate of iron release from the C-lobe (7-fold to 11-fold) and slows the rate of iron release from the N-lobe (6-fold to 15-fold), making them more equivalent and producing an increase in the net rate of iron removal from Fe₂hTF. Calculated cooperativity factors, in addition to plots of time-dependent species distributions in the absence and in the presence of the TFR, clearly illustrate the differences. Accurate rate constants for the pH and salt-induced conformational changes in each lobe precisely delineate how delivery of iron within the physiologically relevant time frame of 2 min might be accomplished.     

The Role of Cognitive and Affective Empathy in Spouses' Support Interactions: An Observational Study

The present study examined how support providers’ empathic dispositions (dispositional perspective taking, empathic concern, and personal distress) as well as their situational empathic reactions (interaction-based perspective taking, empathic concern, and personal distress) relate to the provision of spousal support during observed support interactions. Forty-five committed couples provided questionnaire data and participated in two ten-minute social support interactions designed to assess behaviors when partners are offering and soliciting social support. A video-review task was used to assess situational forms of perspective taking (e.g., empathic accuracy), empathic concern and personal distress. Data were analyzed by means of the multi-level Actor-Partner Interdependence Model. Results revealed that providers scoring higher on affective empathy (i.e., dispositional empathic concern), provided lower levels of negative support. In addition, for male partners, scoring higher on cognitive empathy (i.e., situational perspective taking) was related to lower levels of negative support provision. For both partners, higher scores on cognitive empathy (i.e., situational perspective taking) correlated with more instrumental support provision. Male providers scoring higher on affective empathy (i.e., situational personal distress) provided higher levels of instrumental support. Dispositional perspective taking was related to higher scores on emotional support provision for male providers. The current study furthers our insight into the empathy-support link, by revealing differential effects (a) for men and women, (b) of both cognitive and affective empathy, and (c) of dispositional as well as situational empathy, on different types of support provision.     

A Cooperative System of Two Species with Bidirectional Interactions

Cooperation between species is often regarded to mean that the increase of each species promotes the growth of the other. The well-known cooperative model is the Lotka–Volterra equations (LVEs). In the LVEs, population densities of species increase infinitely as the cooperation is strong, which is called the divergence problem. Moreover, LVEs never exhibit an Allee effect in the case of obligate cooperation. In order to avoid these problems, several models have been established although most of them are rather complex. In this paper, we consider a cooperative system of two species with bidirectional interactions, in which each species also has negative feedback on the other. Population densities of the species will not increase infinitely because of the limited resource and negative feedback. Then, we focus on an extended lattice model of cooperation, which is deduced from reactions on lattice and has the same form as that of LVEs. In the case of obligate cooperation, the model predicts an Allee effect. Global dynamics of the system exhibit essential features of cooperation and basic mechanisms by which the cooperation can lead to coexistence/extinction of species. Intermediate cooperation is shown to be beneficial in cooperation under certain conditions, while extremely strong cooperation is demonstrated to lead to extinction of one/both species. Numerical simulations confirm and extend our results.