bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the Factor Structures of the 55- and 22-Item Versions of the Conformity to Masculine Norms Inventory
Authors: Owen Jesse
Published: May 2010

The current study examined the psychometric properties of the abbreviated versions, 55- and 22-items, of the Conformity to Masculine Norms Inventory (CMNI). The authors tested the factor structure for the 11 subscales of the CMNI-55 and the global masculinity factor for the CMNI-55 and the CMNI-22. In a clinical sample of men and women ( n = 522), the results supported the 11-factor model. Furthermore, the factor structure was invariant for men and women. The higher order model, which tested the utility of the global masculine score, demonstrated marginal fit. The factor structures for the global masculinity score for the CMNI-22 demonstrated poor fit. Collectively, the results suggest that the CMNI-55 is better represented in a multidimensional construct. The subscales’ alpha levels and factor loadings were, generally, within acceptable limits. Gender and ethnic mean level differences are also reported.
Men’s Preferences for Sexually Transmitted Infection Care Services in a Low-Income Community Clinic Setting in New York City
Authors: Holloway Ian W. , Jones Heidi E. , Bell David L. , Westhoff Carolyn L.
Published: May 2010

A self-administered anonymous waiting room survey was used to evaluate men’s preferences on testing, notification, and treatment for sexually transmitted infections (STIs) in a community clinic in Upper Manhattan in 2007. Sixty-seven percent of eligible men ( n = 199) participated. Most were willing to collect a urine sample at home (71%, n = 140) or at the clinic (87%, n = 171). Respondents preferred learning of a positive STI test result by phone (67%, n = 123). However, men were willing to receive results by text (65%, n = 127) or e-mail (61%, n = 121). Most (83%, n = 162) reported they would be (very) likely to take STI medication brought to them by a partner. Twenty-one percent reported previous gonorrhea or Chlamydia infection ( n = 41). Of these, 39% ( n = 16) had received medication to bring their partner, and almost all ( n = 14/16) reported their partner took the medicine. Multiple options for STI testing, notification, and treatment are recommended to maximize service use among men, including providing patient-delivered partner therapy.
Some practical problems in implementing randomization
Authors: Downs Matt , Tucker Kathryn , Christ-Schmidt Heidi , Wittes Janet
Published: May 2010

Background While often theoretically simple, implementing randomization to treatment in a masked, but confirmable, fashion can prove difficult in practice.

Purpose At least three categories of problems occur in randomization: (1) bad judgment in the choice of method, (2) design and programming errors in implementing the method, and (3) human error during the conduct of the trial. This article focuses on these latter two types of errors, dealing operationally with what can go wrong after trial designers have selected the allocation method.

Results We offer several case studies and corresponding recommendations for lessening the frequency of problems in allocating treatment or for mitigating the consequences of errors. Recommendations include: (1) reviewing the randomization schedule before starting a trial, (2) being especially cautious of systems that use on-demand random number generators, (3) drafting unambiguous randomization specifications, (4) performing thorough testing before entering a randomization system into production, (5) maintaining a dataset that captures the values investigators used to randomize participants, thereby allowing the process of treatment allocation to be reproduced and verified, (6) resisting the urge to correct errors that occur in individual treatment assignments, (7) preventing inadvertent unmasking to treatment assignments in kit allocations, and (8) checking a sample of study drug kits to allow detection of errors in drug packaging and labeling.

Limitations Although we performed a literature search of documented randomization errors, the examples that we provide and the resultant recommendations are based largely on our own experience in industry-sponsored clinical trials. We do not know how representative our experience is or how common errors of the type we have seen occur.

Conclusions Our experience underscores the importance of verifying the integrity of the treatment allocation process before and during a trial. Clinical Trials 2010; 7: 235—245. http://ctj.sagepub.com
Who Sees Human?
Authors: Waytz Adam , Cacioppo John , Epley Nicholas
Published: May 2010

Anthropomorphism is a far-reaching phenomenon that incorporates ideas from social psychology, cognitive psychology, developmental psychology, and the neurosciences. Although commonly considered to be a relatively universal phenomenon with only limited importance in modern industrialized societies—more cute than critical—our research suggests precisely the opposite. In particular, we provide a measure of stable individual differences in anthropomorphism that predicts three important consequences for everyday life. This research demonstrates that individual differences in anthropomorphism predict the degree of moral care and concern afforded to an agent, the amount of responsibility and trust placed on an agent, and the extent to which an agent serves as a source of social influence on the self. These consequences have implications for disciplines outside of psychology including human–computer interaction, business (marketing and finance), and law. Concluding discussion addresses how understanding anthropomorphism not only informs the burgeoning study of nonpersons, but how it informs classic issues underlying person perception as well.
Detecting and Correcting the Lies That Data Tell
Authors: Schmidt Frank
Published: May 2010

Because of the way in which data are typically analyzed and interpreted, they frequently lie to researchers, leading to conclusions that are not only false but more complex than the underlying reality. The several examples of this presented in this article illustrate the possibility that although data may appear to indicate complex phenomena at the surface structure level, the phenomena may be quite simple at the deep structure level, suggesting the possibility of applying Occam’s razor to achieve the scientific goal of parsimony. The approaches to data analysis described in this article may also lead to a solution to the serious problem of construct proliferation in psychology by demonstrating that many constructs are redundant with other existing constructs. The major obstacles to these outcomes are researchers' continued reliance on the use of statistical significance testing in data analysis and interpretation and the failure to correct for the distorting effects of sampling error, measurement error, and other artifacts. Some of these problems have been addressed by the now widespread use of meta-analysis, but examination of the meta-analyses appearing in Psychological Bulletin from 1978 to 2006 shows that most employ a statistically inappropriate model for meta-analysis (the fixed effects model) and that 90% do not correct for the biasing effects of measurement error. Hence, there is still a long way to go in the improvement of data analysis and interpretation methods.
Rethinking Social Desirability Scales
Authors: Uziel Liad
Published: May 2010

Social desirability (specifically, impression management) scales are widely used by researchers and practitioners to screen individuals who bias self-reports in a self-favoring manner. These scales also serve to identify individuals at risk for psychological and health problems. The present review explores the evidence with regard to the ability of these scales to achieve these objectives. In the first part of the review, I present six criteria to evaluate impression management scales and conclude that they are unsatisfactory as measures of response style. Next, I explore what individual differences in impression management scores actually do measure. I compare two approaches: a defensiveness approach, which argues that these scales measure defensiveness that stems from vulnerable self-esteem, and an adjustment approach, which suggests that impression management is associated with personal well-being and interpersonal adjustment. Data from a wide variety of fields including social behavior, affect and well-being, health, and job performance tend to favor the adjustment approach. Finally, I argue that scales measuring impression management should be redefined as measures of interpersonally oriented self-control that identify individuals who demonstrate high levels of self-control, especially in social contexts.
A New Social-Cognitive Developmental Perspective on Prejudice
Authors: Rutland Adam , Killen Melanie , Abrams Dominic
Published: May 2010

We argue that prejudice should be investigated in the context of social-cognitive development and the interplay between morality and group identity. Our new perspective examines how children consider group identity (and group norms) along with their developing moral beliefs about fairness and justice. This is achieved by developing an integrated framework drawing on developmental and social psychological theories of prejudice. This synthesis results in a perspective that provides a more contextualized analysis of prejudice development than that previously offered by developmental theories. We describe research that supports our view that social norms, intergroup contact, and perceived outgroup threat affect the relative weight children place on moral and group-based criteria during the development of prejudice.
Renovating the Pyramid of Needs
Authors: Kenrick Douglas T. , Griskevicius Vladas , Neuberg Steven L. , Schaller Mark
Published: May 2010

Maslow’s pyramid of human needs, proposed in 1943, has been one of the most cognitively contagious ideas in the behavioral sciences. Anticipating later evolutionary views of human motivation and cognition, Maslow viewed human motives as based in innate and universal predispositions. We revisit the idea of a motivational hierarchy in light of theoretical developments at the interface of evolutionary biology, anthropology, and psychology. After considering motives at three different levels of analysis, we argue that the basic foundational structure of the pyramid is worth preserving, but that it should be buttressed with a few architectural extensions. By adding a contemporary design feature, connections between fundamental motives and immediate situational threats and opportunities should be highlighted. By incorporating a classical element, these connections can be strengthened by anchoring the hierarchy of human motives more firmly in the bedrock of modern evolutionary theory. We propose a renovated hierarchy of fundamental motives that serves as both an integrative framework and a generative foundation for future empirical research.
A Theory of Human Needs Should Be Human-Centered, Not Animal-Centered
Authors: Kesebir Selin , Graham Jesse , Oishi Shigehiro
Published: May 2010

Kenrick et al. (2010 , this issue) make an important contribution by presenting a theory of human needs within an evolutionary framework. In our opinion, however, this framework bypasses the human uniqueness that Maslow intended to capture in his theory. We comment on the unique power of culture in shaping human motivation at the phylogenetic, ontogenetic, and proximate levels. We note that culture–gene coevolution may be a more promising lead to a theory of human motivation than a mammalcentric evolutionary perspective.
The Purpose-Driven Life
Authors: Ackerman Joshua M. , Bargh John A.
Published: May 2010

The resurgence of motivation in social psychology has been a welcome addition to the cognitive revolution, though a theory-based approach to motivational content has remained conspicuously absent. Kenrick, Griskevicius, Neuberg, and Schaller (2010 , this issue) dust off Maslow’s hierarchy of needs and find this content in the form of evolutionarily inspired, fundamental motives. Their new framework unites functional, developmental, and proximal levels of analysis by showing how these levels complement rather than compete with each other. We highlight what we see as the especially valuable features of this framework and discuss its relevance for research on goal conflict, multigoal priming, and recent studies of goal scaffolding. We also suggest one main tweak to the theoretical foundation presented here that may bear greater empirical fruit. In sum, Kenrick and colleagues have reinvigorated a classic theory by integrating it with a modern understanding of human behavior’s evolutionary roots.
Human Motives, Happiness, and the Puzzle of Parenthood
Authors: Lyubomirsky Sonja , Boehm Julia K.
Published: May 2010

It is presumed that happiness, and its associated positive emotions, signal to the individual that an adaptive problem has been solved, thus allowing her to shift attention to other concerns, perhaps those “higher” on the revised motivational hierarchy proposed by Kenrick et al (2010 , this issue). In this commentary, we present a sampling of longitudinal and experimental evidence supporting two predictions: (a) that people will feel happy after realizing fundamental human motives, and (b) that in turn, the experience of happiness will galvanize people to fulfill these very motives. However, one conspicuous exception to our argument that happiness is both a consequence and a stimulus of human motives is parenthood, which paradoxically is associated with decrements in well-being. Two broad sets of explanations to account for this puzzle are discussed. The first involves evolutionary accounts: that children interfere with lower level needs, that short-term costs of having children are outweighed by long-term benefits, and that the modern-day context of raising children is at odds with our ancestors’ environments. The second possibility involves measurement: namely, problems with study designs and the difficulty of capturing on paper or computer screen what is precisely so wonderful and elusive that children grant their parents.
Pyramid Power
Authors: Schaller Mark , Neuberg Steven L. , Griskevicius Vladas , Kenrick Douglas T.
Published: May 2010

Four thoughtful commentaries identify important issues and insights pertaining to the pyramid of needs presented by Kenrick, Griskevicius, Neuberg, and Schaller (2010 , this issue). Here, we offer additional thoughts on some of these issues and insights, with an emphasis on the logical implications that result from an evolutionary analysis of fundamental human needs.
Ann Saunders: Costume and Maney Publishing
Authors: Rosindale Liz
Published: May 2010

In 1976 the Costume Society commenced its association with W. S. Maney & Son Ltd of Leeds as printer and distributor of Costume. Nearly four decades later this relationship continues, with Maney now taking the role of the Society's publishing partner. This paper gives some details of the production of the journal over this time, drawn together from the virtually complete archive of production and costing records held by Maney; it also provides a brief insight into the relationship between the publisher and journal editor. The paper is adapted and extended from a speech originally given at Ann Saunder's retirement party held at the London office of Maney Publishing, Carlton House Terrace, London, on 11 September 2008.
The 'Empresse of Flowers': The Significance of Floral Imagery in Two Portraits of Elizabeth I at Jesus College, Oxford
Authors: Hayward Maria
Published: May 2010

This paper will consider the significance of flowers in Elizabeth I's portraiture and dress, and it will do so by focusing on two portraits of the queen at Jesus College, Oxford.
The Story of a Shirt: A Cautionary Tale with an Unexpected Ending
Authors: Levey Santina M.
Published: May 2010

This article demonstrates how tracing the history of an altered garment can be as complex and unexpected as the plot of a good detective story.
The Origins of Dress History and Cesare Vecellio's 'pourtraits of attire'
Authors: Bridgeman Jane
Published: May 2010

This article discusses possible reasons for the creation of Degli Habiti Antichi, et Moderni. It is suggested that Vecellio's achievement in describing dress with a combination of illustrative woodcuts and descriptive prose may be celebrated as the first modern history of dress.
Arnold Bennett, Edith Wharton and the 'Minotaur of Time'
Authors: Ribeiro Aileen
Published: May 2010

One of the most potent ways in which the past resonates in the present is via clothing; it is both so distant and yet so familiar to us, and so effective at recalling both a vanished period, and the intimacy of personal emotions. A comparison of the ways dress is used in Arnold Bennett's The Old Wives' Tale and Edith Wharton's The Age of Innocence is the focus of this essay.
Aagot Noss and Her Lifetime Research
Authors: Finch Karen
Published: May 2010

The work of the distinguished Norwegian folk dress historian, Aagot Noss, is considered, and her eleven books on folk dress and its customs, based on fieldwork for the Norwegian Folk Museum, are described and discussed.
Th17/Treg ratio in human graft-versus-host disease
Authors: Ratajczak Philippe , Janin Anne , Peffault de Latour Regis , Leboeuf Christophe , Desveaux Allison , Keyvanfar Keyvan , Robin Marie , Clave Emmanuel , Douay Corine , Quinquenel Anne , Pichereau Claire , Bertheau Philippe , Mary Jean Yves , Socié Gérard
Published: May 2010

Th17 cells have never been explored in human graft-versus-host disease (GVHD). We studied the correlation between the presence of Th17 cells with histologic and clinical parameters. We first analyzed a cohort of 40 patients with GVHD of the gastrointestinal tract. Tumor necrosis factor (TNF), TNF receptors, and Fas expression, and apoptotic cells, CD4+IL-17+ cells (Th17), and CD4+Foxp3+ cells (Treg) were quantified. A Th17/Treg ratio less than 1 correlated both with the clinical diagnosis (P < .001) and more than 2 pathologic grades (P < .001). A Th17/Treg ratio less than 1 also correlated with the intensity of apoptosis of epithelial cells (P = .03), Fas expression in the cellular infiltrate (P = .003), TNF, and TNF receptor expression (P < .001). We then assessed Th17/Treg ratio in 2 other independent cohorts; a second cohort of 30 patients and confirmed that Th17/Treg ratio less than 1 correlated with the pathologic grade of GI GVHD. Finally, 15 patients with skin GVHD and 11 patients with skin rash but without pathologic GVHD were studied. Results in this third cohort of patients with skin disease confirmed those found in patients with GI GVHD. These analyses in 96 patients suggest that Th17/Treg ratio could be a sensitive and specific pathologic in situ biomarker of GVHD.
Thermal stability, pH dependence and inhibition of four murine kynurenine aminotransferases
Authors: Han Qian , Cai Tao , Tagle Danilo A , Li Jianyong
Published: May 2010

Background

Kynurenine aminotransferase (KAT) catalyzes the transamination of kynunrenine to kynurenic acid (KYNA). KYNA is a neuroactive compound and functions as an antagonist of alpha7-nicotinic acetylcholine receptors and is the only known endogenous antagonist of N-methyl-D-aspartate receptors. Four KAT enzymes, KAT I/glutamine transaminase K/cysteine conjugate beta-lyase 1, KAT II/aminoadipate aminotransferase, KAT III/cysteine conjugate beta-lyase 2, and KAT IV/glutamic-oxaloacetic transaminase 2/mitochondrial aspartate aminotransferase, have been reported in mammalian brains. Because of the substrate overlap of the four KAT enzymes, it is difficult to assay the specific activity of each KAT in animal brains.

Results

This study concerns the functional expression and comparative characterization of KAT I, II, III, and IV from mice. At the applied test conditions, equimolar tryptophan with kynurenine significantly inhibited only mouse KAT I and IV, equimolar methionine inhibited only mouse KAT III and equimolar aspartate inhibited only mouse KAT IV. The activity of mouse KAT II was not significantly inhibited by any proteinogenic amino acids at equimolar concentrations. pH optima, temperature preferences of four KATs were also tested in this study. Midpoint temperatures of the protein melting, half life values at 65°C, and pKa values of mouse KAT I, II, III, and IV were 69.8, 65.9, 64.8 and 66.5°C; 69.7, 27.4, 3.9 and 6.5 min; pH 7.6, 5.7, 8.7 and 6.9, respectively.

Conclusion

The characteristics reported here could be used to develop specific assay methods for each of the four murine KATs. These specific assays could be used to identify which KAT is affected in mouse models for research and to develop small molecule drugs for prevention and treatment of KAT-involved human diseases.
High amino acid diversity and positive selection at a putative coral immunity gene (tachylectin-2)
Authors: Hayes Marshall L , Eytan Ron I , Hellberg Michael E
Published: May 2010

Background

Genes involved in immune functions, including pathogen recognition and the activation of innate defense pathways, are among the most genetically variable known, and the proteins that they encode are often characterized by high rates of amino acid substitutions, a hallmark of positive selection. The high levels of variation characteristic of immunity genes make them useful tools for conservation genetics. To date, highly variable immunity genes have yet to be found in corals, keystone organisms of the world's most diverse marine ecosystem, the coral reef. Here, we examine variation in and selection on a putative innate immunity gene from Oculina, a coral genus previously used as a model for studies of coral disease and bleaching.

Results

In a survey of 244 Oculina alleles, we find high nonsynonymous variation and a signature of positive selection, consistent with a putative role in immunity. Using computational protein structure prediction, we generate a structural model of the Oculina protein that closely matches the known structure of tachylectin-2 from the Japanese horseshoe crab (Tachypleus tridentatus), a protein with demonstrated function in microbial recognition and agglutination. We also demonstrate that at least three other genera of anthozoan cnidarians (Acropora, Montastrea and Nematostella) possess proteins structurally similar to tachylectin-2.

Conclusions

Taken together, the evidence of high amino acid diversity, positive selection and structural correspondence to the horseshoe crab tachylectin-2 suggests that this protein is 1) part of Oculina's innate immunity repertoire, and 2) evolving adaptively, possibly under selective pressure from coral-associated microorganisms. Tachylectin-2 may serve as a candidate locus to screen coral populations for their capacity to respond adaptively to future environmental change.
Griseofulvin stabilizes microtubule dynamics, activates p53 and inhibits the proliferation of MCF-7 cells synergistically with vinblastine
Authors: Rathinasamy Krishnan , Jindal Bhavya , Asthana Jayant , Singh Parminder , Balaji Petety V , Panda Dulal
Published: May 2010

Background

Griseofulvin, an antifungal drug, has recently been shown to inhibit proliferation of various types of cancer cells and to inhibit tumor growth in athymic mice. Due to its low toxicity, griseofulvin has drawn considerable attention for its potential use in cancer chemotherapy. This work aims to understand how griseofulvin suppresses microtubule dynamics in living cells and sought to elucidate the antimitotic and antiproliferative action of the drug.

Methods

The effects of griseofulvin on the dynamics of individual microtubules in live MCF-7 cells were measured by confocal microscopy. Immunofluorescence microscopy, western blotting and flow cytometry were used to analyze the effects of griseofulvin on spindle microtubule organization, cell cycle progression and apoptosis. Further, interactions of purified tubulin with griseofulvin were studied in vitro by spectrophotometry and spectrofluorimetry. Docking analysis was performed using autodock4 and LigandFit module of Discovery Studio 2.1.

Results

Griseofulvin strongly suppressed the dynamic instability of individual microtubules in live MCF-7 cells by reducing the rate and extent of the growing and shortening phases. At or near half-maximal proliferation inhibitory concentration, griseofulvin dampened the dynamicity of microtubules in MCF-7 cells without significantly disrupting the microtubule network. Griseofulvin-induced mitotic arrest was associated with several mitotic abnormalities like misaligned chromosomes, multipolar spindles, misegregated chromosomes resulting in cells containing fragmented nuclei. These fragmented nuclei were found to contain increased concentration of p53. Using both computational and experimental approaches, we provided evidence suggesting that griseofulvin binds to tubulin in two different sites; one site overlaps with the paclitaxel binding site while the second site is located at the αβ intra-dimer interface. In combination studies, griseofulvin and vinblastine were found to exert synergistic effects against MCF-7 cell proliferation.

Conclusions

The study provided evidence suggesting that griseofulvin shares its binding site in tubulin with paclitaxel and kinetically suppresses microtubule dynamics in a similar manner. The results revealed the antimitotic mechanism of action of griseofulvin and provided evidence suggesting that griseofulvin alone and/or in combination with vinblastine may have promising role in breast cancer chemotherapy.
A systematic review and meta-analysis of bone metabolism in prostate adenocarcinoma
Authors: Serpa Neto Ary , Tobias-Machado Marcos , Esteves Marcos AP , Senra Marília D , Wroclawski Marcelo L , Fonseca Fernando LA , dos Reis Rodolfo B , Pompeo Antônio CL , Del Giglio Auro
Published: May 2010

Background

Osteoporosis could be associated with the hormone therapy for metastatic prostate carcinoma (PCa) and with PCa per se. The objective of this review is to determine the incidence of bone loss and osteoporosis in patients with PCa who are or are not treated with hormone therapy (ADT).

Methods

The Medline, Embase, Cancerlit, and American Society of Clinical Oncology Abstract databases were searched for published studies on prostate cancer and bone metabolism. The outcomes assessed were: fracture, osteoporosis and osteopenia.

Results

Thirty-two articles (116,911 participants) were included in the meta-analysis. PCa patients under ADT had a higher risk of osteoporosis (RR, 1.30; p < 0.00001) and a higher risk of fractures (RR, 1.17; p < 0.00001) as compared to patients not under ADT. The total bone mineral density was lower in patients under ADT when compared with patients not under ADT (p = 0.031) but it was similar to bone mineral density found in healthy controls (p = 0.895). The time of androgen deprivation therapy correlated negatively with lumbar spine and total hip bone mineral density (Spearman's rho = -0.490 and -0.773; p = 0.028 and 0.001, respectively) and with total hip t score (Spearman's rho = -0.900; p = 0.037).

Conclusion

We found consistent evidence that the use of androgen deprivation therapy in patients with PCa reduces bone mineral density, increasing the risk of fractures in these patients.
MyD88-dependent and independent pathways of Toll-Like Receptors are engaged in biological activity of Triptolide in ligand-stimulated macrophages
Authors: Premkumar Vummidigiridhar , Dey Moul , Dorn Ruth , Raskin Ilya
Published: May 2010

Background

Triptolide is a diterpene triepoxide from the Chinese medicinal plant Tripterygium wilfordii Hook F., with known anti-inflammatory, immunosuppressive and anti-cancer properties.

Results

Here we report the expression profile of immune signaling genes modulated by triptolide in LPS induced mouse macrophages. In an array study triptolide treatment modulated expression of 22.5% of one hundred and ninety five immune signaling genes that included Toll-like receptors (TLRs). TLRs elicit immune responses through their coupling with intracellular adaptor molecules, MyD88 and TRIF. Although it is known that triptolide inhibits NFκB activation and other signaling pathways downstream of TLRs, involvement of TLR cascade in triptolide activity was not reported. In this study, we show that triptolide suppresses expression of proinflammatory downstream effectors induced specifically by different TLR agonists. Also, the suppressive effect of triptolide on TLR-induced NFκB activation was observed when either MyD88 or TRIF was knocked out, confirming that both MyD88 and TRIF mediated NFκB activation may be inhibited by triptolide. Within the TLR cascade triptolide downregulates TLR4 and TRIF proteins.

Conclusions

This study reveals involvement of TLR signaling in triptolide activity and further increases understanding of how triptolide activity may downregulate NFκB activation during inflammatory conditions.
Pristimerin induces apoptosis in imatinib-resistant chronic myelogenous leukemia cells harboring T315I mutation by blocking NF-κB signaling and depleting Bcr-Abl
Authors: Lu Zhongzheng , Jin Yanli , Chen Chun , Li Juan , Cao Qi , Pan Jingxuan
Published: May 2010

Background

Chronic myelogenous leukemia (CML) is characterized by the chimeric tyrosine kinase Bcr-Abl. Bcr-Abl-T315I is the notorious point mutation that causes resistance to imatinib and the second generation tyrosine kinase inhibitors, leading to poor prognosis. CML blasts have constitutive p65 (RelA NF-κB) transcriptional activity, and NF-κB may be a potential target for molecular therapies in CML that may also be effective against CML cells with Bcr-Abl-T315I.

Results

In this report, we discovered that pristimerin, a quinonemethide triterpenoid isolated from Celastraceae and Hippocrateaceae, inhibited growth and induced apoptosis in CML cells, including the cells harboring Bcr-Abl-T315I mutation. Additionally, pristimerin inhibited the growth of imatinib-resistant Bcr-Abl-T315I xenografts in nude mice. Pristimerin blocked the TNFα-induced IκBα phosphorylation, translocation of p65, and expression of NF-κB-regulated genes. Pristimerin inhibited two steps in NF-κB signaling: TAK1→IKK and IKK→IκBα. Pristimerin potently inhibited two pairs of CML cell lines (KBM5 versus KBM5-T315I, 32D-Bcr-Abl versus 32D-Bcr-Abl-T315I) and primary cells from a CML patient with acquired resistance to imatinib. The mRNA and protein levels of Bcr-Abl in imatinib-sensitive (KBM5) or imatinib-resistant (KBM5-T315I) CML cells were reduced after pristimerin treatment. Further, inactivation of Bcr-Abl by imatinib pretreatment did not abrogate the TNFα-induced NF-κB activation while silencing p65 by siRNA did not affect the levels of Bcr-Abl, both results together indicating that NF-κB inactivation and Bcr-Abl inhibition may be parallel independent pathways.

Conclusion

To our knowledge, this is the first report to show that pristimerin is effective in vitro and in vivo against CML cells, including those with the T315I mutation. The mechanisms may involve inhibition of NF-κB and Bcr-Abl. We concluded that pristimerin could be a lead compound for further drug development to overcome imatinib resistance in CML patients.
Aldosterone-producing adenoma and other surgically correctable forms of primary aldosteronism
Authors: Amar Laurence , Plouin Pierre-François , Steichen Olivier
Published: May 2010

Surgically correctable forms of primary aldosteronism are characterized by unilateral aldosterone hypersecretion and renin suppression, associated with varying degrees of hypertension and hypokalemia. Unilateral aldosterone hypersecretion is caused by an aldosterone-producing adenoma (also known as Conn's adenoma and aldosteronoma), primary unilateral adrenal hyperplasia and rare cases of aldosterone-producing adrenocortical carcinoma. In these forms, unilateral adrenalectomy can cure aldosterone excess and hypokalemia, but not necessarily hypertension. The prevalence of primary aldosteronism in the general population is not known. Its prevalence in referred hypertensive populations is estimated to be between 6 and 13%, of which 1.5 to 5% have an aldosterone-producing adenoma or primary unilateral adrenal hyperplasia. Taking into account referral biases, the prevalence of surgically correctable primary aldosteronism is probably less than 1.5% in the hypertensive population and less than 0.3% in the general adult population. Surgically correctable primary aldosteronism is sought in patients with hypokalemic, severe or resistant forms of hypertension. Recent recommendations suggest screening for primary aldosteronism using the aldosterone to renin ratio. Patients with a raised ratio then undergo confirmatory suppression tests. The differential diagnosis of hypokalemic hypertension with low renin includes mineralocorticoid excess, with the mineralocorticoid being cortisol or 11-deoxycorticosterone, apparent mineralocorticoid excess, pseudo-hypermineralocorticoidism in Liddle syndrome or exposure to glycyrrhizic acid. Once the diagnosis is confirmed, adrenal computed tomography is performed for all patients. If surgery is considered, taking into consideration the clinical context and the desire of the patient, adrenal vein sampling is performed to detect whether or not aldosterone hypersecretion is unilateral. Laparoscopic surgery for unilateral aldosterone hypersecretion is associated with a morbidity of about 8%, with most complications being minor. It generally results in the normalization of aldosterone secretion and kalemia, and in a large decrease in blood pressure, but normotension without treatment is only achieved in half of all cases. Normotension following adrenalectomy is more frequent in young patients with recent hypertension than in patients with long-standing hypertension or a family history of hypertension.
Kidney function of HIV‐infected children in Lagos, Nigeria: using Filler's serum cystatin C‐based formula
Authors: Esezobor Christopher I , Iroha Edna , Oladipo Olajumoke , Onifade Elizabeth , Soriyan Oyetunji O , Akinsulie Adebola O , Temiye Edamisan O , Ezeaka Chinyere
Published: May 2010

Background

Limited data is available on kidney function in HIV‐infected children in sub‐Saharan Africa. In addition, malnutrition in these children further reduces the utility of diagnostic methods such as creatinine‐based estimates of glomerular filtration rate. We determined the serum cystatin C level and estimated glomerular filtration rate of 60 antiretroviral‐naïve, HIV‐infected children and 60 apparently healthy age and sex matched children.

Methods

Serum cystatin C level was measured using enzyme‐linked immunosorbent assay technique, while glomerular filtration rate was estimated using Filler's serum cystatin C formula. Student t test, Mann Whitney U test, Pearson chi square and Fisher's exact test were used, where appropriate, to test difference between groups.

Results

Compared to the controls, the HIV‐infected group had significantly higher median (interquartile range) serum cystatin C levels {0.77 (0.29) mg/l versus 0.66 (0.20) mg/l; p = 0.025} and a higher proportion of children with serum cystatin C level >1 mg/l {10 (16.7%) versus one (1.7%); p = 0.004}. The HIV‐infected children had a mean (± SD) eGFR of 96.8 (± 36.1) ml/min/1.73 m2 compared with 110.5 (± 27.8) ml/min/1.73 m2 in the controls (p = 0.021). After controlling for age, sex and body mass index, only the study group (HIV infected versus control) remained a significant predictor of serum cystatin C level (β = ‐0.216, p = 0.021). The proportion of HIV‐infected children with eGFR <60 ml/min/1.73 m2 was eight (13.3%) versus none (0%) in the control group (p = 0.006). However, the serum cystatin C level, eGFR and proportions of children with serum cystatin C level >1 mg/l and eGFR <60 ml/min/1.73 m2 were not significantly different between the HIV‐infected children with advanced disease and those with milder disease.

Conclusions

HIV‐infected children in Nigeria have higher serum cystatin C level and lower eGFR compared to age and sex matched controls.
Hepatic failure, neonatal hemochromatosis and porto-pulmonary hypertension in a newborn with trisomy 21 - a case report
Authors: Neil Erin , Cortez Josef , Joshi Aparna , Bawle Erawati V , Poulik Janet , Zilberman Mark , El-Baba Mohammad F , Sood Beena G
Published: May 2010

Liver failure in neonates is a rare but often fatal disease. Trisomy 21 is not usually associated with significant infantile liver disease. If present, hepatic dysfunction in an infant with Trisomy 21 is likely to be attributed to transient myeloproliferative disorder with hepatic infiltration by hematopoietic elements and may be associated with secondary hemosiderosis. A less commonly recognized cause of liver failure in neonates with Trisomy 21 is neonatal hemochromatosis (NH); this association has been reported in nine cases of Trisomy 21 in literature. NH is a rare, severe liver disease of intra-uterine onset that is characterized by neonatal liver failure and hepatic and extrahepatic iron accumulation that spares the reticuloendothelial system. NH is the most frequently recognized cause of liver failure in neonates and the commonest indication for neonatal liver transplantation. Although porto-pulmonary hypertension (PPH) has been reported as a complication of liver failure in adults and older children, this has not been reported in neonates with liver failure of any etiology. This is probably due to the rarity of liver failure in newborns, delayed diagnosis and high mortality. The importance of recognizing PPH is that it is reversible with liver transplantation but at the same time increases the risk of post-operative mortality. Therefore, early diagnosis of PPH is critical so that early intervention can improve the chances of successful liver transplantation. We report for the first time the association of liver failure with porto-pulmonary hypertension secondary to NH in an infant with Trisomy 21.
Increased inflammation and impaired resistance to Chlamydophila pneumoniae infection in Dusp1-/- mice: critical role of IL-6
Authors: Rodriguez Nuria , Dietrich Harald , Mossbrugger Ilona , Weintz Gabriele , Scheller Jürgen , Hammer Michael , Quintanilla-Martinez Leticia , Rose-John Stefan , Miethke Thomas , Lang Roland
Published: May 2010

Dendritic cells interact with T cells in intestinal mucosa in an MHCII-dependent manner, suggesting presentation outside organized lymphoid tissue may be important in determining T cell phenotype.

The MAPK phosphatase DUSP1 is an essential negative regulator of TLR-triggered innate immune activation. Here, we have investigated the impact of DUSP1 on inflammatory and antimicrobial host responses to the intracellular pathogen Chlamydophila pneumoniae. Following nasal infection, DUSP1-deficient mice mounted an enhanced pulmonary cytokine (IL-1β, IL-6) and chemokine response (CCL3, CCL4, CXCL1, CXCL2), leading to increased leukocyte infiltration. Of interest, the increased inflammatory response, in the absence of DUSP1, was associated with higher bacterial numbers in the lungs, although the expression of IFN-γ and critical antichlamydial effector molecules, such as iNOS, was intact. Blockade of IL-6 trans-signaling by injection of a soluble gp130-Fc fusion protein corrected the overshooting chemokine production as well as the increased chlamydial load in Dusp1−/− mice. Furthermore, IL-6 enhanced the replication of C. pneumoniae in embryonic fibroblasts in vitro. These data show that DUSP1 is required to achieve a balanced response to chlamydial infection and identify IL-6 as critical for amplifying inflammation and benefiting chlamydial growth through direct effects on infected cells.
The bone marrow: a site of neutrophil clearance
Authors: Rankin Sara M
Published: May 2010

Review discusses evidence that the bone marrow is an important site of neutrophil clearance under homeostatic conditions.

Abstract

Neutrophils, an essential component of the innate immune system, are produced at a rate 1011 cells/day and are consequently the most abundant leukocyte in the blood. These granulocytes have a relatively short half-life (6–8 h) in the blood, and as a result of the cytotoxic nature of their contents, it is critical that there are mechanisms in place for the efficient clearance of these effete cells from the circulation. Although macrophages of the reticuloendothelial system are positioned ideally to recognize and phagocytose apoptotic neutrophils in the circulation, this review challenges the current dogma that neutrophils are cleared primarily in the liver and spleen, presenting the evidence that the bone marrow is also an important site of neutrophil clearance under homeostatic conditions. Furthermore, a role for the CXCL12/CXCR4 chemokine axis in the trafficking of senescent neutrophils back to the bone marrow for clearance is described.
CCR1- and CCR5-mediated inactivation of leukocytes by a nonglycosaminoglycan (non-GAG)-binding variant of n-Nonanoyl-CCL14 (NNY-CCL14)
Authors: Gupta Shipra , Rieder Sebastian , Richter Rudolf , Schulz-Maronde Sandra , Manns Johanna , Escher Sylvia E , Heitland Aleksandra , Mack Matthias , Forssmann Wolf-Georg , Elsner Jörn , Forssmann Ulf
Published: May 2010

The non-glycosaminoglycan binding NNY-CCL14(G,A) is a potential lead for an anti-inflammatory therapy exerting its effects via multiple chemokine receptors.

Intervention on chemokine receptors to prevent directional leukocyte migration is a potential therapeutic strategy. NNY-CCL14 is a CD26-resistant lead molecule, which exerts its effects on multiple chemokine receptors (CCR1, CCR2, CCR3, and CCR5). The inhibitory effects of NNY-CCL14 in murine models of allergic airway inflammation have been assigned to its interaction with CCR1 and CCR5. In this study, a non-GAG-binding variant of NNY-CCL14 was generated by mutating basic amino acids within the identified GAG-binding 49BBXB52 motif. This CD26-resistant, non-GAG binding variant, NNY-CCL14(G,A), does not promote CCR1-dependent cell arrest on modeled endothelium. Its biological activity tested on human and murine chemokine receptors revealed distinguishing properties to NNY-CCL14. As suggested by EC50 values for intracellular calcium mobilization, NNY-CCL14(G,A) demonstrated a reduced ability to activate hCCR1, but internalization and desensitization of hCCR1 were unperturbed. Surprisingly, its activity on hCCR3 was strongly reduced, and it did not internalize mCCR3. A significantly reduced chemotactic activity of eosinophils and monocytes was observed. All biological effects mediated by NNY-CCL14(G,A) via hCCR5 and mCCR5 showed no difference to NNY-CCL14. In mice treated i.v. with NNY-CCL14(G,A), a sustained in vivo down-modulation of CCR5 was achieved over 3 h. Therefore, NNY-CCL14(G,A) inactivates leukocytes by desensitizing and internalizing multiple chemokine receptors, thus rendering them unresponsive to further stimulation by natural ligands. When administered systemically, NNY-CCL14(G,A) may modulate leukocyte functions prior to their interaction with other endothelium-bound chemokines expressed under pathophysiological conditions, such as allergic inflammation.
The mitochondrial import gene tomm22 is specifically required for hepatocyte survival and provides a liver regeneration model
Authors: Curado Silvia , Ober Elke A. , Walsh Susan , Cortes-Hernandez Paulina , Verkade Heather , Koehler Carla M. , Stainier Didier Y. R.
Published: May 2010

Understanding liver development should lead to greater insights into liver diseases and improve therapeutic strategies. In a forward genetic screen for genes regulating liver development in zebrafish, we identified a mutant – oliver – that exhibits liver-specific defects. In oliver mutants, the liver is specified, bile ducts form and hepatocytes differentiate. However, the hepatocytes die shortly after their differentiation, and thus the resulting mutant liver consists mainly of biliary tissue. We identified a mutation in the gene encoding translocase of the outer mitochondrial membrane 22 (Tomm22) as responsible for this phenotype. Mutations in tomm genes have been associated with mitochondrial dysfunction, but most studies on the effect of defective mitochondrial protein translocation have been carried out in cultured cells or unicellular organisms. Therefore, the tomm22 mutant represents an important vertebrate genetic model to study mitochondrial biology and hepatic mitochondrial diseases. We further found that the temporary knockdown of Tomm22 levels by morpholino antisense oligonucleotides causes a specific hepatocyte degeneration phenotype that is reversible: new hepatocytes repopulate the liver as Tomm22 recovers to wild-type levels. The specificity and reversibility of hepatocyte ablation after temporary knockdown of Tomm22 provides an additional model to study liver regeneration, under conditions where most hepatocytes have died. We used this regeneration model to analyze the signaling commonalities between hepatocyte development and regeneration.
Ras controls melanocyte expansion during zebrafish fin stripe regeneration
Authors: Lee Yoonsung , Nachtrab Gregory , Klinsawat Pai W. , Hami Danyal , Poss Kenneth D.
Published: May 2010

Regenerative medicine for complex tissues like limbs will require the provision or activation of precursors for different cell types, in the correct number, and with the appropriate instructions. These strategies can be guided by what is learned from spectacular events of natural limb or fin regeneration in urodele amphibians and teleost fish. Following zebrafish fin amputation, melanocyte stripes faithfully regenerate in tandem with complex fin structures. Distinct populations of melanocyte precursors emerge and differentiate to pigment regenerating fins, yet the regulation of their proliferation and patterning is incompletely understood. Here, we found that transgenic increases in active Ras dose-dependently hyperpigmented regenerating zebrafish fins. Lineage tracing and marker analysis indicated that increases in active Ras stimulated the in situ amplification of undifferentiated melanocyte precursors expressing mitfa and kita. Active Ras also hyperpigmented early fin regenerates of kita mutants, which are normally devoid of primary regeneration melanocytes, suppressing defects in precursor function and survival. By contrast, this protocol had no noticeable impact on pigmentation by secondary regulatory melanocyte precursors in late-stage kita regenerates. Our results provide evidence that Ras activity levels control the repopulation and expansion of adult melanocyte precursors after tissue loss, enabling the recovery of patterned melanocyte stripes during zebrafish appendage regeneration.
J-Aggregation of Zinc 31,131-Dihydroxychlorins by Exclusive Coordination Bonding between 31-Hydroxy Group and Central Zinc Atom
Authors: Kunieda Michio , Tamiaki Hitoshi
Published: May 2010

Zinc 31,131-dihydroxychlorin lacking an exo-five-membered E-ring was prepared as a model of natural bacteriochlorophyll-d possessing 31-OH and 13-C=O groups. The synthetic zinc complex has the 13-CH2OH instead of the 13-C=O and self-aggregated in a nonpolar organic solvent, giving slipped and π-overlapped molecular stackings (J-aggregates) with red-shifted and broadened electronic absorption bands. For the intermolecular interactions among the J-aggregates, coordination bonding of the 31-OH (not 131-OH) with the central Zn was utilized.
Optical Resolution of Chiral Buckybowls by Chiral HPLC
Authors: Tsuruoka Ryoji , Higashibayashi Shuhei , Ishikawa Takeharu , Toyota Shinji , Sakurai Hidehiro
Published: May 2010

Optical resolution of chiral buckybowls, C3 symmetric trimethylsumanene derivatives, was achieved by chiral HPLC. Enantiomeric excess (ee) of enatioselectively prepared trimethyltris(trimethylsilyl)sumanene was determined by the chiral HPLC analysis. The enantiomers of racemic trimethylsumanenetrione were separated, and the bowl inversion energy barrier was determined by the CD spectra.