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Objective: To investigate whether poverty and lack of insurance are associated with perceived racial and ethnic bias in health care.Data Source: 2001 Survey on Disparities in Quality of Health Care, a nationally representative telephone survey. We use data on black, Hispanic, and white adults who have a regular physician (N=4,556).Study Design: We estimate multivariate logistic regression models to examine the effects of poverty and lack of health insurance on perceived racial and ethnic bias in health care for all respondents and by racial, ethnic, and language groups.Principal Findings: Controlling for sociodemographic and other factors, uninsured blacks and Hispanics interviewed in English are more likely to report racial and ethnic bias in health care compared with their privately insured counterparts. Poor whites are more likely to report racial and ethnic bias in health care compared with other whites. Good physician-patient communication is negatively associated with perceived racial and ethnic bias.Conclusions: Compared with their more socioeconomically advantaged counterparts, poor whites, uninsured blacks, and some uninsured Hispanics are more likely to perceive that racial and ethnic bias operates in the health care they receive. Providing health insurance for the uninsured may help reduce this perceived bias among some minority groups. [ABSTRACT FROM AUTHOR]

Are competent actors still trusted when they promote themselves? The answer to this question could have far-reaching implications for understanding trust production in a variety of economic exchange settings in which ability and impression management play vital roles, from succeeding in one's job to excelling in the sales of goods and services. Much social science research assumes an unconditional positive impact of an actor's ability on the trust placed in that actor: in other words, competence breeds trust. In this report, however, we challenge this assumption. Across a series of experiments, we manipulated both the ability and the self-promotion of a trustee and measured the level of trust received. Employing both online laboratory studies ( n = 5,606) and a field experiment ( n = 101,520), we find that impression management tactics (i.e., self-promotion and intimidation) can substantially backfire, at least for those with high ability. An explanation for this effect is encapsuled in attribution theory, which argues that capable actors are held to higher standards in terms of how kind and honest they are expected to be. Consistent with our social attribution account, mediation analyses show that competence combined with self-promotion decreases the trustee's perceived benevolence and integrity and, in turn, the level of trust placed in that actor.

Background: Plasmid DNA has been widely used in vaccination as well as in cell and gene therapy. It exists in multiple isoforms, including supercoiled, nicked or open circular and linear forms. Regulatory agencies recommend having more than 80% of the supercoiled isoform for the bulk release of plasmid products; thus, it should be analyzed accordingly., Methods and Results: The traditional analysis method for plasmid DNA is agarose gel electrophoresis. However, due to time-consuming manual sample loading, visualization, and data analysis, it has limitations in obtaining consistently quantitative results. In this short communication, we introduced a fast, sensitive, and robust plasmid analysis method using capillary gel electrophoresis with laser-induced fluorescence detection (CGE-LIF). CGE-LIF analysis of the supercoiled isoform and its open circular counterpart was completed in 20 minutes with excellent sensitivity by using a common fluorescent DNA binding dye. The advantage of the method was demonstrated by the purity analysis of two large plasmids (7 kb and 10 kb). The fully automated sample loading, separation and data analysis featured enhanced assay repeatability and ease of quantitation over agarose gel electrophoresis., Conclusion: As a worked example, analysis of plasmid samples treated at elevated temperature during an accelerated stability test also demonstrated the applicability of CGE-LIF to monitor plasmid topology and possible degradation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: Little is known about how long-term cancer survivors adapt in the realm of work and finances, and whether there are differences in these adaptations based on overall health status. We hypothesize that survivors with better health-related quality of life (HQL) have better work and financial outcomes., Study Design: Cross-sectional study with 200 adult recipients of autologous hematopoietic cell transplantation (HCT) 3-26 years after transplant using self-administered questionnaires and medical records extraction., Main Outcome Measures: Questionnaires assessed work status, financial satisfaction, and perceived improvements in financial status since transplant., Results: Nearly half the survivors were employed (37.2% full-time, 8.7% part-time); 37.2% had retired. Higher scores on the functional HQL were linked to a lower relative risk of having retired (RRR 0.85, CI 0.75-0.98) and of being neither in the workforce nor retired (RRR 0.84, CI 0.72-0.99) compared with working full-time. Higher functional HQL also related to higher financial satisfaction (b 0.06, CI 0.01-0.10) and increased odds of perceived improvements in one's financial situation since transplant (OR 1.15, CI 1.04-1.17). Patients receiving HCT at age ≥60 were more likely than counterparts receiving HCT at age 18-39 to work part-time (RRR 18.24, 95% CI 1.19-280.24) and to have retired (Model 1 RRR 579.14, 95% CI 49.53-6771.54) than to be working full-time., Conclusions: Survivors with poorer HQL may be at risk for overall poorer work and financial adaptation. Interventions targeting this group and specifically focusing on re-integration into the world of paid work should be considered., (Copyright © 2017. Published by Elsevier B.V.)

To provide social exchange on a global level, sharing-economy companies leverage interpersonal trust between their members on a scale unimaginable even a few years ago. A challenge to this mission is the presence of social biases among a large heterogeneous and independent population of users, a factor that hinders the growth of these services. We investigate whether and to what extent a sharing-economy platform can design artificially engineered features, such as reputation systems, to override people's natural tendency to base judgments of trustworthiness on social biases. We focus on the common tendency to trust others who are similar (i.e., homophily) as a source of bias. We test this argument through an online experiment with 8,906 users of Airbnb, a leading hospitality company in the sharing economy. The experiment is based on an interpersonal investment game, in which we vary the characteristics of recipients to study trust through the interplay between homophily and reputation. Our findings show that reputation systems can significantly increase the trust between dissimilar users and that risk aversion has an inverse relationship with trust given high reputation. We also present evidence that our experimental findings are confirmed by analyses of 1 million actual hospitality interactions among users of Airbnb., Competing Interests: Conflict of interest statement: A.G. is a data scientist at Airbnb who performed the experiments that rely on the company’s private data. Paolo Parigi began working at Uber after the research design, experiment execution, data analysis, and writing of the study were completed.

Why do people distrust others in social exchange? To what degree, if at all, is distrust subject to genetic influences, and thus possibly heritable, and to what degree is it nurtured by families and immediate peers who encourage young people to be vigilant and suspicious of others? Answering these questions could provide fundamental clues about the sources of individual differences in the disposition to distrust, including how they may differ from the sources of individual differences in the disposition to trust. In this article, we report the results of a study of monozygotic and dizygotic female twins who were asked to decide either how much of a counterpart player's monetary endowment they wanted to take from their counterpart (i.e., distrust) or how much of their own monetary endowment they wanted to send to their counterpart (i.e., trust). Our results demonstrate that although the disposition to trust is explained to some extent by heritability but not by shared socialization, the disposition to distrust is explained by shared socialization but not by heritability. The sources of distrust are therefore distinct from the sources of trust in many ways., Competing Interests: The authors declare no conflict of interest.

Despite the popularity of the notion that social cohesion in the form of dense social networks promotes cooperation in Prisoner's Dilemmas through reputation, very little experimental evidence for this claim exists. We address this issue by testing hypotheses from one of the few rigorous game-theoretic models on this topic, the Raub & Weesie model, in two incentivized lab experiments. In the experiments, 156 subjects played repeated two-person PDs in groups of six. In the "atomized interactions" condition, subjects were only informed about the outcomes of their own interactions, while in the "embedded" condition, subjects were informed about the outcomes of all interactions in their group, allowing for reputation effects. The design of the experiments followed the specification of the RW model as closely as possible. For those aspects of the model that had to be modified to allow practical implementation in an experiment, we present additional analyses that show that these modifications do not affect the predictions. Contrary to expectations, we do not find that cooperation is higher in the embedded condition than in the atomized interaction. Instead, our results are consistent with an interpretation of the RW model that includes random noise, or with learning models of cooperation in networks.

Using semi-structured interviews with 50 hematopoietic stem cell transplantation (HSCT) recipients who were 2 to 22 years post-transplant, this study investigates cancer survivors' interpretations of their economic and work-related experiences during and after treatment. Survivors described a variety of challenges in these areas, including job insecurity, discrimination, career derailment, the lack of career direction, delayed goals, financial losses, insurance difficulties, constraints on job mobility, and physical/mental limitations. Survivors described the ways these challenges were offset by external factors that helped them to navigate these difficulties and buffered the negative financial and career-related impacts. Good health insurance, favorable job characteristics, job accommodations, and financial buffers were prominent offsetting factors. Most survivors, however, were also forced to rely on individual behavioral and interpretative strategies to cope with challenges. Behavioral strategies included purposeful job moves, retraining, striving harder, and retiring. Some strategies were potentially problematic, such as acquiring large debt. Interpretive strategies included reprioritizing and value shifts, downplaying the magnitude of cancer impact on one's life, denying the causal role of cancer in negative events, making favorable social comparisons, and benefit finding. Post-treatment counseling and support services may assist survivors in identifying available resources and useful strategies to improve long-term adaptation in the career and financial realms.

How does lacking vs. possessing power in a social exchange affect people's trust in their exchange partner? An answer to this question has broad implications for a number of exchange settings in which dependence plays an important role. Here, we report on a series of experiments in which we manipulated participants' power position in terms of structural dependence and observed their trust perceptions and behaviors. Over a variety of different experimental paradigms and measures, we find that more powerful actors place less trust in others than less powerful actors do. Our results contradict predictions by rational actor models, which assume that low-power individuals are able to anticipate that a more powerful exchange partner will place little value on the relationship with them, thus tends to behave opportunistically, and consequently cannot be trusted. Conversely, our results support predictions by motivated cognition theory, which posits that low-power individuals want their exchange partner to be trustworthy and then act according to that desire. Mediation analyses show that, consistent with the motivated cognition account, having low power increases individuals' hope and, in turn, their perceptions of their exchange partners' benevolence, which ultimately leads them to trust.

This paper describes the use of an anionic ion-pair reagent (IPR) to impove the ultraviolet (UV) detection and hydrophobic retention of polar and UV transparent cations. Anionic IPR added to the mobile phase forms an ion-pair with cations. Formation of the ion-pair causes a redshift in the absorption wavength, making it possible for direct UV detection of UV-inactive cations. The ion-pairs with increased hydrophobicity were separated by reversed phase liquid chromatography (RPLC). Different perfluorinated caboxylic acids (trifluoroacetic acid, heptafluorobutyric acid, nonafluoropentanoic acid) were evaluted as IPR in the separation and detection of the common cations sodium, ammonium and Tris(hydroxymethyl)aminomethane (Tris). The effects of the IPR type and concentration on separation and detection have been investigated to understand the separation and detection mechanisms. The optimal separation and detection condtions were attained with mobile phase containing 0.1% nonafluoropentanoic acid and with the UV detection at 210nm. UV detection and charged aerosol detection (CAD) were compared in the quantitation of the cations. The limit of quantitation (LOQ) of sodium and Tris with UV detection is comparable to that by CAD. The LOQ of ammonium with UV detection (1ppm or 3ng) is about 20-fold lower than that (20ppm or 60ng) by CAD. The RPLC-UV method was used to monitor ammonium clearance during ultrafiltration and diafiltration in the manfucaturing of biopharmceutical drug substance., (Copyright © 2015 Elsevier B.V. All rights reserved.)

A violation of trust can have quite different consequences, depending on the nature of the relationship in which the trust breach occurs. In this article, we identify a key relationship characteristic that affects trust recovery: the extent of relationship experience before the trust breach. Across two experiments, this investigation establishes the behavioral effect that greater relationship experience before a trust breach fosters trust recovery. A neuroimaging experiment provides initial evidence that this behavioral effect is possible because of differential activation of two brain systems: while decision making after early trust breaches engages structures of a controlled social cognition system (C-system), specifically the anterior cingulate cortex and lateral frontal cortex, decision making after later trust breaches engages structures of an automatic social cognition system (X-system), specifically the lateral temporal cortex. The present findings make contributions to both social psychological theory and the neurophysiology of trust.

N-linked glycosylation can influence the biological activity and safety of an antibody as well as be a measure of the consistency of the production process. The released N-glycans is an important part of the development of a therapeutic antibody. The traditional method for N-glycan analysis requires complex and laborious sample preparation and lengthy analysis time. Two preparation steps with limited control are removal of the antibody backbone by ice-cold ethanol precipitation and water removal before 2-AB fluorescent dye labeling. Simplification of the sample preparation and better control of key steps that allows for the characterization/quantitation of glycans during all stages of development of a therapeutic antibody is desired. Recently Prozyme introduced a rapid deglycosylation kit and a rapid tagging kit that address some of these issues. The deglycosylation kit immobilizes the antibody on a membrane, thereby eliminating the precipitation step. An instant fluorescent tag kit eliminates the water removal before the 2-AB labeling step. In addition use of a new chromatography column can improve the glycan resolution and shorten the analysis time. The evaluation and qualification of the Rapid Deglycosylation Kit (RDK) and instant 2-AB tagging with the improved chromatography are highlighted., (Copyright © 2012 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.)

Objective: The aim of this preliminary study was to examine the impact of participation in an illness self-management recovery program (Wellness Recovery Action Planning-WRAP) on the ability of individuals with severe mental illnesses to achieve key recovery related outcomes., Methods: A total of 30 participants from three mental health centers were followed immediately before and after engaging in a 12-week WRAP program., Results: Three paired sample t-tests were conducted to determine the effectiveness of WRAP on hope, recovery orientation, and level of symptoms. A significant positive time effect was found for hope and recovery orientation. Participants showed improvement in symptoms, but the change was slightly below statistical significance., Conclusions: These preliminary results offer promising evidence that the use of WRAP has a positive effect on self-reported hope and recovery-related attitudes, thereby providing an effective complement to current mental health treatment.

In a series of experiments, we demonstrate that certain players of an economic game reject unfair offers even when this behavior increases rather than decreases inequity. A substantial proportion (30-40%, compared with 60-70% in the standard ultimatum game) of those who responded rejected unfair offers even when rejection reduced only their own earnings to 0, while not affecting the earnings of the person who proposed the unfair split (in an impunity game). Furthermore, even when the responders were not able to communicate their anger to the proposers by rejecting unfair offers in a private impunity game, a similar rate of rejection was observed. The rejection of unfair offers that increases inequity cannot be explained by the social preference for inequity aversion or reciprocity; however, it does provide support for the model of emotion as a commitment device. In this view, emotions such as anger or moral disgust lead people to disregard the immediate consequences of their behavior, committing them to behave consistently to preserve integrity and maintain a reputation over time as someone who is reliably committed to this behavior.

We examine whether racial/ethnic/language-based variation in measured levels of patients' trust in a physician depends on the survey items used to measure that trust. Survey items include: (1) a direct measure of patients' trust that the doctor will put the patient's medical needs above all other considerations, and (2) three indirect measures of trust asking about expectations for specific physician behaviors, including referring to a specialist, being influenced by insurance rules, and performing unnecessary tests. Using a national survey, we find lower scores on indirect measures of trust in a physician among minority users of health care services than among non-Hispanic white users. In contrast, the direct measure of trust does not differ among non-Hispanic whites and nonwhites once we control for potential confounding factors. The results indicate that racial/ethnic/language-based differences exist primarily in those aspects of patients' trust in a physician that reflect specific physician behaviors.

Objectives: To examine whether fiduciary trust in a physician is related to unmet health care needs and delayed care among patients who have a regular physician, and to investigate whether the relationships between trust and unmet health care needs and delays in care are attenuated for disadvantaged patients who face structural obstacles to obtaining health care., Data Sources/study Setting: The 1998-1999 Community Tracking Study (CTS) Household Survey, a cross-sectional sample representative of the U.S. noninstitutionalized population. This study analyzes adults who usually see the same physician for their health care (n = 29,994)., Study Design: We estimated logistic regression models of the association of trust with unmet health care needs and delayed care. We tested interactions between trust and barriers to obtaining care, including minority race/ethnicity, poverty, and the absence of health insurance. Control variables included patients' sociodemographic characteristics, health status, satisfaction with the available choice of primary physicians, and the number of physician visits during the last year., Principal Findings: Patients' fiduciary trust in a physician is negatively associated with the likelihood of reporting delayed care and unmet health care needs among most patients. Among African Americans, Hispanics, the poor, and the uninsured, however, fiduciary trust is not significantly associated with the likelihood of delayed care. For unmet needs, only the uninsured have no significant association with trust., Conclusions: Results show that trust is associated with improved chances of getting needed care across most subgroups of the population, although this relationship varies by subpopulation.

A series of studies have been conducted by experimental and theoretical methods on the synthesis, structures, and reactions of CpRh boryl complexes that are likely intermediates in the rhodium-catalyzed regioselective, terminal functionalization of alkanes. The photochemical reaction of CpRh(eta(6)-C(6)Me(6)) with pinacolborane (HBpin) generates the bisboryl complex CpRh(H)(2)(Bpin)(2) (2), which reacts with neat HBpin to generate CpRh(H)(Bpin)(3) (3). X-ray diffraction, density functional theory (DFT) calculations, and NMR spectroscopy suggest a weak, but measurable, B-H bonding interaction. Both 2 and 3 dissociate HBpin and coordinate PEt(3) or P(p-Tol)(3) to generate the conventional rhodium(III) species CpRh(PEt(3))(H)(Bpin) (4) and CpRh[P(p-tol)(3)](Bpin)(2) (5). Compounds 2 and 3 also react with alkanes and arenes to form alkyl- and arylboronate esters at temperatures similar to or below those of the catalytic borylation of alkanes and arenes. Further, these compounds were observed directly in catalytic reactions. The enthalpies and free energies for generation of the 16-electron intermediate and for the C-H bond cleavage and B-C bond formation have been calculated with DFT. These results strongly suggest that the C-H bond cleavage process occurs by a metal-assisted sigma-bond metathesis mechanism to generate a borane complex that isomerizes if necessary to place the alkyl group cis to the boryl group. This complex with cis boryl and alkyl groups then undergoes B-C bond formation by a second sigma-bond metathesis to generate the final functionalized product.

Context: Little is known about whether some features of managed care widen disparities in patients' evaluations of primary care., Objectives: We investigated whether the magnitudes of racial and ethnic/language-based differences in patients' evaluations of the quality of primary care vary by capitation and gatekeeping., Design: We used a telephone survey of a representative sample of the US noninstitutionalized population, Community Tracking Study Household Survey 1998-1999, and Followback Survey of respondents' insurance administrators., Setting and Participants: Our sample was privately insured adults who saw a physician at least once during the year preceding the interview and whose last visit was to a primary care physician., Main Outcome Measures: We measured patients' evaluations of (1) how well the physician listened, (2) how well the physician explained, and (3) how thorough and careful the physician was during the last visit., Results: Significant white-minority differences emerge more often in plans using capitation or gatekeeping than in other plans. The gaps in patients' evaluations of their primary care providers' (PCP) explanations and thoroughness between whites and Hispanics interviewed in English are larger when the PCP is capitated than when the PCP is not capitated. The gap in the evaluations of their PCP's explanations by whites and Hispanics interviewed in English is larger in plans that require referrals for specialist visits than in other plans. The magnitude of racial and ethnic/language-based gaps for Hispanics interviewed in Spanish, blacks, and Native American/Asian/Pacific Islanders do not differ by capitation and gatekeeping., Conclusion: English-speaking Hispanics' perceptions of the quality of primary care may be more dissimilar from whites' when capitation or gatekeeping are used than when these policies are not used.

The compounds, where Cp' = C(5)H(5), a series, and C(5)H(4)Me, b series, are generated via treatment of with HB(C(6)F(5))(2). When allowed to undergo irreversible methane loss in the presence of an excess of the sterically modest alkynes 2-butyne or phenylacetylene, the putative intermediates 1a and 1b are trapped as the tantala-3-boratacyclopentene compounds 2 and 3, respectively. In these complexes, the alkyne and borataalkene ligands have reductively coupled at the d(2) tantalum center. For the unsymmetrical alkyne, a kinetic product resulting from coupling in the opposite regiochemical sense is observed; the thermodynamic products 3-t incorporate the phenyl group in the alpha position of the tantalaboratacyclic ring. Two of these compounds (2b and 3b-t) were characterized crystallographically. For bulkier alkynes (diphenylacetylene, 1-phenyl-1-propyne, and 3-hexyne), intermediates with similar spectroscopic properties to the tantala-3-boratacyclopentenes were observed, but the ultimate products were the vinylalkylidene compounds 5-(R,R'). Compound 5-(Ph,Me) was characterized crystallographically, and it was found that the vinylalkylidene binds to the metal in an eta(1)-bonding mode, with the tantalum center receiving further ligation through a hydridoborate moiety. Mechanistic studies suggest that these products arise via retrocyclization of the tantala-3-boratacyclopentenes formed kinetically. These studies represent the first studies concerning the reactivity of a borataalkene ligand at a transition metal center and show that it can behave in an "olefin-like" manner, despite having a more flexible array of bonding modes available to it than an olefin.

Many countries are importing managed care and price competition from the US to improve the performance of their health care systems. However, relatively little is known about how power is organized and exercised in the US health care system to control costs, improve quality and achieve other objectives. To close this knowledge gap, we applied social exchange theory to examine the power relations between purchasers, managed care organizations, providers and patients in the US health care system at three interrelated levels: (1) exchanges between purchasers and managed care organizations (MCOs); (2) exchanges between MCOs and physicians; and (3) exchanges between physicians and patients. The theory and evidence indicated that imbalanced exchange, or dependence, at all levels prompts behavior to move the exchange toward power balance. Collective action is a common strategy at all levels for reducing dependence and therefore, increasing power in exchange relations. The theoretical and research implications of exchange theory for the comparative study of health care systems are discussed.

The HIV-1 REV protein binds to the stem II region of the REV-responsive element (RNA). Studies to further define the RNA sequence and structure specifically bound by REV protein identify a minimal RNA element of 40 nucleotides. Analysis of RNA fragments by gel retardation and filter binding suggest that a core element composed of one particular stem with flanking sequences capable of forming a second double stranded region is essential for specific recognition by REV protein. Stable REV-RNA complexes are formed in a stoichiometry of 1 REV: 1 RNA. The minimal RNA element binds 1 REV molecule while the stem II saturates at 3 REV molecules per RNA. These results establish that REV recognizes a primary binding site within the RRE and support the notion that the initial viral transcript binding event involves a monomeric REV protein.

Adipsin, a serine protease homolog, is synthesized and secreted by adipose cells and is found in the bloodstream. The expression of adipsin messenger RNA (mRNA) and protein was analyzed in rodents during metabolic perturbations and in several experimental models of obesity. Adipsin mRNA abundance is increased in adipose tissue during fasting in normal rats and in diabetes due to streptozotocin-induced insulin deficiency. Adipsin mRNA abundance decreased during the continuous infusion of glucose, which induces a hyperglycemic, hyperinsulinemic state that is accompanied by an increased adipose mass; it is suppressed (greater than 100-fold) in two strains of genetically obese mice (db/db and ob/ob), compared to their congenic counterparts, and is also reduced when obesity is induced chemically by injection of monosodium glutamate into newborn mice. Circulating adipsin protein is decreased in these animal models of obesity, as determined by immunoblotting with antisera to adipsin. Little change in adipsin expression is observed in a model of obesity obtained by pure overfeeding of normal rats (cafeteria model). These data suggest a possible role for adipsin in the above-mentioned disordered metabolic states, and raise the possibility that adipsin expression may be used to distinguish obesities that arise from certain genetic or metabolic defects from those that result from pure overfeeding.

Bacteriophage T4 infection is known to induce the formation of a complex of enzymes effecting the de novo synthesis of deoxyribonucleoside triphosphates, which in turn are channeled into T4 DNA replication. The first step in this pathway is catalyzed by a ribonucleoside diphosphate reductase, comprised of subunits coded by T4 genes nrdA and nrdB. Maximum rates of synthesis of the pyrimidine deoxyribonucleotides and of DNA replication in vivo also require a type II DNA topoisomerase encoded by T4 genes 39, 52, and 60. We report the identification of a unique mutant, nrdB93, and the suppression of its defective deoxyribonucleotide synthesis by a gene 39 mutation, 39-01. After infection by 39-01, DNA synthesis and plaque formation were temperature-sensitive, but nearly wild type rates of deoxyribonucleotide synthesis were retained at all temperatures. The nrdB93 mutation had a profound effect on deoxyribonucleotide synthesis at 41 degrees C; even at the permissive temperature of 30 degrees C, synthesis was reduced to 30% of that of wild type or 39-01. However, on infection at 30 degrees C by the double mutant, 39-01 nrdB93, the level of deoxyribonucleotide synthesis again reached that of wild type phage infections; involvement of the comparable host enzyme in the suppression process has been excluded. Suppression of the effect of nrdB93 by 39-01 implicates the gene 39 product in the regulation of nrdB expression. The accompanying paper (Cook, K. S., Wirak, D. O., Seasholtz, A. F., and Greenberg, G. R. (1988) J. Biol. Chem. 263, 6202-6208) examines the nature of the suppression process at the molecular level.

Adipsin expression at the protein and mRNA levels is greatly reduced in several distinct syndromes of obesity in the mouse: genetic obesity due to the db/db and ob/ob genes, and a chemically induced model secondary to neonatal exposure to monosodium glutamate. We considered first the possibility that the adipsin gene might be identical to the db or ob locus and the lowered expression of this protein might result from a mutation in this gene. We show here that the adipsin structural gene is located on chromosome 10 and hence is physically distinct from any obesity genes so far identified in the mouse. A major role for the adrenal gland and adrenal glucocorticoids in the aberrant regulation of adipsin in these models of obesity is indicated by several experiments. Adrenalectomy of the ob/ob mouse raises the circulating levels of adipsin protein and the amount of this mRNA in epididymal fat pads (5-fold), although neither is increased to the levels seen in lean controls. Exogenous administration of corticosterone completely blocks the effects of adrenalectomy on adipsin, suggesting that the effect of this endocrine ablation is through reduction of adrenal glucocorticoids. Corticosterone administration also causes suppression in the levels of adipsin mRNA and protein in lean mice, although this decrease is never as severe as that seen in obese mice. The effect of exogenous corticosterone in lean mice occurs within 2 days and hence is not secondary to the obesity which these hormones eventually elicit. These results indicate that glucocorticoids can regulate adipsin expression in vivo and strongly suggest that the hyperglucocorticoid state seen in certain obese models plays a significant role in lowering adipsin mRNA and protein levels. Quantitative analysis of these experiments suggests that other as yet unknown neuroendocrine factors also function to suppress adipsin in obesity.

We previously have isolated cDNA clones for several mRNAs that increase in abundance during the differentiation of 3T3 adipocytes but whose physiological role is unknown. We show here that a mRNA that is complementary to one of these clones and encodes a protein of 28 kDa is expressed abundantly in mouse fat pads but not in several other mouse tissues. Sequence analysis of the corresponding cDNA clone indicated that the encoded protein shows 30% overall amino acid homology to several serine proteases including trypsin, chymotrypsin, and elastase. Homology is much higher (64%) between the 28-kDa protein and regions that are strongly conserved among the members of the serine protease family. The derived protein also has key features characteristic of active serine proteases, including the histidine, aspartic acid, and serine residues, which comprise the charge relay system, and a potential cleavage site for activation of the zymogen. Primer extension analysis performed to obtain the sequence of the 5' end of mRNA that encodes the 28-kDa protein indicates that two forms of this mRNA exist and probably arise through alternative splicing. The two mRNAs encode signal sequences that differ by the deletion of one amino acid near the predicted cleavage site of the signal peptide. These results demonstrate that adipocyte differentiation is accompanied by the expression of mRNA encoding a serine protease homologue that can be synthesized with two different signal peptides.

This paper presents a theory of the effects of rate review on hospital operations and organization. Its purpose is to explain the way in which hospitals have responded to regulation. In the development of this theory, the hospital product was viewed as a bundle of services, rate review was looked upon as a ceiling on the value of the bundle. The ceiling creates an incentive to remove elements from the bundle, i.e., to reduce 'quality'. When quality is variable, the effect on utilization becomes indeterminate. The model argues, among other things, that the hospital will change its service complement and its contractural arrangements with physicians and other hospitals. An extension of the organizational theory literature leads to implications concerning the ordering of hospital responses to regulation. The growing body of empirical literature on the effects of hospital rate review is used as an initial test of the major thrusts of the theory. A suggested agenda for further empirical work also is presented.

Adipsin is a serine protease that is secreted by adipocytes into the bloodstream; it is deficient in several animal models of obesity, representing a striking example of defective gene expression in this disorder. Recombinant mouse adipsin was purified and its biochemical and enzymatic properties were studied in order to elucidate the function of this protein. Activated adipsin has little or no proteolytic activity toward most substrates but has the same activity as human complement factor D, cleaving complement factor B when it is complexed with activated complement component C3. Like authentic factor D, adipsin can activate the alternative pathway of complement, resulting in red blood cell lysis. Decreased (58 to 80 percent) complement factor D activity, relative to lean controls, was observed as a common feature of several experimental models of obesity, including the ob/ob, db/db, and monosodium glutamate (MSG)-injected mouse and the fa/fa rat. These results suggest that adipsin and the alternative pathway of complement may play an unexpected but important role in the regulation of systemic energy balance in vivo.

Profiles of bacteriophage T4 early proteins resolved by a two-dimensional nonequilibrium pH gradient electrophoresis system (P. Z. O'Farrell, H. M. Goodman, and P. H. O'Farrell, Cell 12:1133--1142, 1977) are presented. Over 65 phage-induced proteins were resolved. Amber or deletion mutants were used to identify 17 proteins in the gel patterns as the products of specific genes.

A preparation of bacteriophage T4-induced deoxyribonucleotide synthetase complex is described. This very large complex of enzymes can be separated by centrifugation at 100,000 X g, by sucrose step gradient centrifugation, or with molecular exclusion columns. By direct assay and by unidimensional and two-dimensional acrylamide electrophoretic separations the following T4-coded enzymes were shown to be associated with the complex: ribonucleoside diphosphate reductase, dCMP deaminase, dCTP/dUTPase, dCMP hydroxymethylase, dTMP synthetase, and DNA polymerase. Other phage-coded prereplicative proteins related to DNA replication and other phage functions such as the proteins coded by genes 32, 46, rIIA, and rIIB as well as many unidentified proteins were also consistently associated with the isolated fractions. T4 DNA topoisomerase, a membrane-bound enzyme, was found in quantity in all purified fractions of the complex, even in preparations apparently free of membrane and of T4 DNA. The functional integrity of a segment of the complex was followed by measuring the conversion of [5-3H]CDP to the level of 5-hydroxymethyl dCMP. This series of reactions requires the actions of T4-coded ribonucleoside diphosphate reductase and its associated reducing system, dCTP/dUTPase and dCMP hydroxymethylase, 3H being lost to water at the last step. In this reaction sequence an intermediate, [5-3H]dCMP, is maintained at low steady state concentrations, and argument is presented that the synthesis of deoxyribonucleotides is channeled and normally tightly coupled to DNA replication. One of the primary characteristics of this complex is its ready dissociation of dilution into smaller complexes of proteins and to the free forms of the proteins. That the complex is held together by weak electrostatic forces was supported by its sensitivity to dissociation at moderate salt concentrations. Not only the enzymes required in deoxyribonucleotide synthesis but T4 DNA polymerase, T4 DNA topoisomerase, and a number of other proteins dissociate to varying degrees from the larger complexes under these conditions.

We have investigated the regulation of mRNA synthesis during 3T3-adipocyte differentiation by measuring the transcription of specific genes in isolated preadipocyte and adipocyte nuclei. Transcription was assayed by hybridization of newly synthesized RNA to cDNA clones coding for glycerophosphate dehydrogenase (GPD), the induced protein of 13K which is shown here to be related to myelin protein P-2, the induced protein of 28K, actin, and two RNAs that are not developmentally regulated. Transcription of GPD and 13K was observed in adipocyte but not preadipocyte nuclei. Actin was transcribed in both types of nuclei but at a lower level in adipocytes. For most of the RNAs examined, there was a consistent relationship between amounts of nuclear transcription and the abundance of the corresponding cytoplasmic mRNA in adipocytes. However, 13K and 28K mRNAs are 10-100 times more abundant than would be predicted by their nuclear transcription alone. Preliminary mRNA turnover experiments in which 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole was used to inhibit mRNA synthesis suggest that these mRNAs are much more stable in the adipocyte cytoplasm than the other mRNAs examined. These results indicate that the transcription of specific genes is increased during adipocyte differentiation and suggest that other levels of control, particularly mRNA stability, may contribute to the relative abundance of certain developmentally-regulated mRNAs in adipocytes.

Bacteriophage T4 ribonucleoside diphosphate reductase consists of alpha 2 and beta 2 subunits encoded by genes nrdA and nrdB, respectively, and plays a central role in the T4-induced deoxyribonucleotide synthetase complex. The accompanying paper describes the decreased rate of synthesis of deoxyribonucleotides after infection by the T4 mutant, nrdB93, and the suppression of this defect by a second mutation in gene 39, coding for one of the three protein chains of T4 DNA topoisomerase. In this study we examined these effects at the protein level. On infection by nrdB93 not only was the beta 93 protein chain altered, as shown by its migration relative to the wild type protein in electrophoretic gels and by its temperature sensitivity, but the infected cells showed very low levels of the protein. However, on infection with the double mutant of nrdB93 and 39-01 (gene 39) the concentration of beta 93 chain returned to the values of beta protein found with wild type phage. A double mutant bearing nrdB93 and an amber mutation of gene 39 also suppressed the nrdB93 defect. By contrast, a temperature-sensitive mutant of gene 39, A41, did not show suppression at either 30 or 41 degrees C. Amber mutations in the two other genes coding for T4 DNA topoisomerase, 52 and 60, did not suppress the defect. We propose that the deficiency in the quantity of beta 93 chain and the suppression of this defect occur at the transcriptional or translational expression of the nrdB93 gene and that a specific domain of the gene 39 protein, not acting in the capacity of T4 DNA topoisomerase, inhibits the expression.

Smith and Mick identify four basic problems with the theory the present writers developed to explain organizational responses (in this case the behavior of hospitals) to regulation. They challenge the basic assumption regarding autonomy, disagree with the implied cause and effect relations between organizational response and regulation, criticize the omission of goals, and claim that the theory has only limited generality. In so doing they state that their primary concern is with "improving our understanding of the limitations and benefits of the theory." Each of the four topics they raise for consideration will receive comment.

The human immunodeficiency virus type 1 (HIV-1) genome encodes the regulatory protein Rev, of relative molecular mass 13,000, which is synthesized from fully processed viral transcripts before synthesis of HIV-1 structural proteins. Rev has been postulated to exert control within the nucleus at the level of messenger RNA processing. The availability of Rev in the nucleus serves to increase the proportion of unspliced and singly spliced mRNA species relative to fully spliced mRNA molecules, resulting in an increased synthesis of viral structural proteins. A highly conserved cis-acting sequence termed the Rev-responsive element (RRE) has been identified in the envelope gene (env) of the viral transcript that seems to control mRNA processing in a Rev-dependent manner. Genetic studies have identified rev gene mutants with dominant phenotypes, supporting the hypothesis that Rev interacts directly with the RRE. Here we demonstrate that Rev protein, purified from Escherichia coli, binds in a sequence-specific manner to the RRE element in vitro.

Adipsin is a serine protease homolog whose primary structure was predicted from the nucleotide sequence of a differentiation-dependent adipocyte messenger RNA. Immunoblots probed with antisera to synthetic peptides identify two forms of adipsin that are synthesized and secreted by 3T3 adipocytes. These proteins of 44 and 37 kilodaltons are converted to 25.5 kilodaltons by enzymatic deglycosylation. Although adipsin is principally synthesized in adipose tissue, it is also produced by sciatic nerve and is found in the bloodstream. Because of the apparent restriction of adipsin synthesis to tissues highly active in lipid metabolism, its presence in serum, and its modulation in altered metabolic states, this molecule may play a previously unrecognized role in systemic lipid metabolism or energy balance.

As a part of the study of the bacteriophage T4-induced deoxyribonucleotide synthetase complex, an investigation has been made of the T4 ribonucleoside diphosphate reductases formed by a series of mutants of nrdA and B, the genes coding, respectively, for the alpha 2 and beta 2 subunits of the enzyme. dATP affinity columns were used to isolate the enzyme by a single-step procedure. The molecular weights of the alpha and beta chains have been found to be 84,000 and 43,500, respectively, by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Since alpha 2 beta 2 is bound to dATP affinity columns through allosteric effector sites on alpha 2, it is possible to monitor the binding of beta 2 to alpha 2. dTTP- and ATP-Sepharose columns did not bind T4 alpha 2 beta 2, although the corresponding nucleoside triphosphates are effectors of the enzyme and although the alpha 2 subunit of the host enzyme binds to these columns. Missense mutants of nrdA and B forming alpha 2 and beta 2 subunits that lacked catalytic activity but retained the ability to form the alpha 2 beta 2 complex have been described. The 50,000-dalton fragment formed by an amber mutant of nrdA did not bind to the dATP affinity column, providing evidence that a region of the carboxyl-terminal segment of the alpha chain is required for retention. The beta 2 subunit appears to protect the alpha 2 protein. On infection by nrdB mutants not forming beta 2, the alpha protein chain was cleaved specifically to form 3 protein chains of 61,000, 57,000, and 24,500 daltons, which retain the ability to bind to dATP-Sepharose. Some effects of mutation on the interaction of the alpha and beta chains of the enzyme with the deoxyribonucleotide synthetase complex have been examined.