bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene–environment Interaction between MBL2 Genotype and Smoking, and the Risk of Gram‐positive Bacteraemia
Authors: Huttunen R. , Aittoniemi J. , Laine J. , Vuento R. , Karjalainen J. , Rovio A. T. , Eklund C. , Hurme M. , Huhtala H. , Syrjänen J.
Published: September 2008

Mannose‐binding lectin (MBL) insufficiency caused by point mutations in the MBL2 gene has been associated with increased susceptibility to bacteraemic infections. We here investigated the effect of MBL2 polymorphisms on the susceptibility and clinical course of bacteraemia. The study cohort comprised 145 patients with bacteraemia and 400 controls. In the case of patients with bacteraemia, laboratory findings and clinical data were registered on admission and during six consecutive days. MBL2 structural polymorphisms at codons 52 (CGT→TGT; designated D or O), 54 (GGC→GAC; B or O) and 57 (GGA→GAA; C or O) in exon 1 of the MBL2 gene and promoter region polymorphisms at position −221 (G→C, designated Y or X alleles) were determined. No difference in MBL2 genotype frequencies between the bacteraemic patients and controls was detected, and MBL2 genotype had no independent effect on mortality, nor disease severity. However, smoking proved a significant risk factor for Gram‐positive (Staphylococcus aureus, Streptococcus pneumoniae or β‐haemolytic streptococci) bacteraemia in patients carrying the variant O allele (53% current smokers in Gram‐positive bacteraemia patients compared with only 21% in controls, odds ratios 4.2, 95% confidence intervals 2.0–9.0; P < 0.001), while it did not have an effect in those homozygous for the A allele. The same effect was not detected in Escherichia coli bacteraemia. In conclusion, MBL2 genotypes representing MBL insufficiency were not associated with the overall risk of bacteraemia or disease severity, but smoking in carriers of the structural variant O allele may have a deleterious effect increasing the risk of Gram‐positive bacteraemia.
Identification of New Loci Controlling Collagen‐induced Arthritis in Mouse Using a Partial Advanced Intercross and Congenic Strains
Authors: Popovic M. , Ahlqvist E. , Rockenbauer E. , Bockermann R. , Holmdahl R.
Published: September 2008

Collagen‐induced arthritis (CIA) is a well studied mouse model of the human disease rheumatoid arthritis (RA). Both CIA and RA are complex diseases affected by multiple genes as well as environmental factors. Identifying the genes that determine susceptibility to arthritis would give invaluable clues to the largely unknown aetiology of RA. In this study, we dissected a known locus, Cia6, as well as a genomic region on chromosome 14 with no previously known arthritis loci, using a partial advanced intercross and a collection of congenic strains. The chromosome 14 congenic fragment, containing the T‐cell receptor alpha (Tcra) locus, was included based on the hypothesis that the Cia6 locus is caused by a polymorphism in the Tcr beta (Tcrb) locus and that the two loci interact. Splitting up the congenic fragments revealed multiple loci affecting arthritis traits as well as production of collagen‐specific autoantibodies. In total seven new loci were identified of which four were in the previously unlinked chromosome 14 region. Both Tcr loci were within CIA loci making them candidate susceptibility genes. The results demonstrate the importance of breaking up genetic regions in smaller fragments to identify the underlying complex set of loci.
Deficiency of the Human Complement Regulatory Protein Factor H Associated with Low Levels of Component C9
Authors: Falcão D. A. , Reis E. S. , Paixão‐Cavalcante D. , Amano M. T. , Delcolli M. I. M. V. , Florido M. P. C. , Albuquerque J. A. T. , Moraes‐Vasconcelos D. , Duarte A. J. , Grumach A. S. , Isaac L.
Published: September 2008

We identified a 4‐year‐old Brazilian boy from a family of Japanese descent and history of consanguinity, who suffered from severe recurrent pneumonia. He carries factor H (FH) deficiency associated with reduced levels of component C9 and low serum levels of C3 and factor B. His mother also presented low levels of these proteins and factor I, while his father and sister had only lower levels of FH. Western blot assays confirmed the complete absence of FH and FHL‐1 polypeptides in this patient. Sequencing of the proband’s FH cDNA revealed a homozygous G453A substitution, encoding an Arg127His change. His mother, father and sister are heterozygous for this substitution. Despite the absence of FH in the plasma, this protein was detected in the patient’s fibroblasts, suggesting that Arg127 may be important for FH secretion. Low concentrations of C9 were detected in the proband serum but no mutations in the patient’s C9 gene or promoter have been identified, suggesting that this is a consequence of uncontrolled complement activation and high C9 consumption.
Characterization of Monoclonal Immunoglobulin A and G Against Shiga Toxin Binding Subunits Produced by Intranasal Immunization
Authors: Tanikawa T. , Ishikawa T. , Maekawa T. , Kuronane K. , Imai Y.
Published: September 2008

Immunoglobulin A (IgA) is considered to play a major role in protection of the mucosal surface. However, its immunological and biological properties have not been extensively studied because the production of IgA class monoclonal antibodies (mAbs) is difficult. We compared the properties of IgA and IgG mAbs against Shiga toxin B subunits (Stx1B). These mAbs were secreted from hybridomas that had been produced from mice after intranasal immunization with recombinant Stx1B and cholera toxin. The dose response curves for the binding of the IgA (clone G2G7) and IgG (clone D11C6) mAbs to immobilized Stx1B were similar, as revealed on ELISA. The majority of the IgA mAb formed dimers while the IgG mAb was monomeric, as judged by immunoblot analysis. The IgG mAb completely inhibited the binding of Stx1B to Burkitt’s lymphoma cell line Ramos, while the inhibition by the IgA mAb was only partial. The IgG mAb was able to neutralize the cytotoxicity of Stx1 holotoxin towards Vero cells, whereas the IgA mAb was not. The binding affinity of each binding site was compared by means of surface plasmon resonance analysis involving a capture method, with which the binding of soluble Stx1B to immobilized mAb was detected. The association rate was similar but the dissociation rate was twofold faster in the case of the IgA mAb, resulting in twofold higher affinity of the IgG mAb. These results suggest that one can obtain high affinity IgA mAb but toxin neutralization is another challenge as to therapeutic antibodies of the IgA class.
Beginning of the End of (Understanding) the Immune Response
Authors: Dembic Z.
Published: September 2008

The algorithm about the workings of the immune system should incorporate in its basic form the ability to explain several basic features: the ability to reject pathogens, to respond differently to invasions by class switching, to retain memory of rejecting past infections, the regulatory T‐cell formation and the acquisition of a life‐long antigen tolerance in adults. The Danger and the two self–non‐self theories – Pathogenicity (Janeway) and the Associated Antigen Recognition (Langman and Cohn) – cannot explain satisfactorily one or more of these issues. By failing to find appropriate solutions to help their corresponding basic algorithms to be operative, these theories negate, instead of finding explanations (no matter how complicated) for interpretations of certain results, one of them being the existence of a regulatory cell as a physiological component of the immune system. On the other hand, the integrity model can incorporate regulatory T cells in a basic algorithm of the workings of the immune system, explaining it as a downregulation of the immune response provided advantageous commensalism prevails over disadvantages of parasitism.
A Novel Tissue Engineering‐based Assay for Immunological Infertility
Authors: Ahangari G. , Naderimanesh H. , Hossein‐Nezhad A. , Zouali M.
Published: September 2008

Antisperm antibodies (ASA) are present in 9–36% of infertile couples, a condition called immunological infertility. The variability of ASA in terms of antigenic specificity and biological effects has made it difficult to design a test able to distinguish reliably between ASA that contribute to infertility and those that do not. To develop a reliable and reproducible method able to detect sperm antibodies, we took advantage of recent progress made in tissue engineering techniques. We used collagen gel as a bio‐scaffold for the production of engineered sperm analogues. The advantages of using collagen gels include biocompatibility, ease of fabrication and low cost. We found that this tissue engineering‐based assay is more specific and more sensitive than a conventional test routinely used for ASA detection. In addition, it exhibited low intra‐ and inter‐variations. We envision the use of this novel approach for the detection of a variety of autoantibodies in autoimmune diseases. In addition to diagnostic purposes, tissue‐engineering based tests could be useful in monitoring treatments with bio‐drugs.
The Group Size Paradox Revisited
Authors: PECORINO PAUL , TEMIMI AKRAM
Published: September 2008

Esteban and Ray (2001)model an increasing marginal cost of effort in providing a public good. If the marginal cost of contribution function has an elasticity greater than 1, then the level of provision is increasing in group size, regardless of the degree of rivalry of the public good. We modify their model to a standard public goods setting, where their results continue to hold. We then add small fixed costs of participation to the model. If the good is sufficiently rival, one ofOlson's (1965)central propositions is restored: public goods will fail to be provided in large groups.
Existence and Uniqueness of Nash Equilibrium in Electoral Competition Games: The Hybrid Case
Authors: SAPORITI ALEJANDRO
Published: September 2008

This paper analyzes the traditional unidimensional, two‐party electoral competition game when parties have mixed motivations, in the sense that they are interested in winning the election, but also in the policy implemented after the contest. In spite of having discontinuous payoffs, this game, referred to as the hybrid election game, is shown to be payoff secure and reciprocally upper semi‐continuous. Conditional payoffs, however, are not quasi‐concave. Hence, the existence of a pure strategy Nash equilibrium (psne) is ensured only if parties have homogenous interests in power. In that case, an equilibrium not only exists, but it is also unique. Instead, if parties have heterogeneous motivations, depending upon the relationship between the electoral uncertainty, the aggregate opportunism, and its distribution across parties, a psne may or may not exist. The mixed extension, however, is always better reply secure. Therefore, a mixed strategy Nash equilibrium does indeed exist.
Bargaining with Rent Seekers
Authors: GLAZER AMIHAI
Published: September 2008

Consider a rent‐seeking game, which has government bargain with firms over dividing the rents. In period 1, each firm can invest to increase the probability that the rent will appear. In period 2, the parties bargain. In equilibrium, though firms will invest more than the socially optimal level, rent‐seeking expenditures may be low. Firms that collude to restrict investment maximize joint profits by investing at a positive, non‐infinitesimal level, and restrict investment even if the cost of rent‐seeking effort is zero.
ANALYSING THE VINLAND MAP: A CRITICAL REVIEW OF A CRITICAL REVIEW*
Authors: TOWE K. M. , CLARK R. J. H. , SEAVER K. A.
Published: September 2008

In an attempt to validate the Vinland Map as a genuine15th century work, Garman

Harbottle (2008

) claims to review critically, and thereby discredit, the archaeometric research undertaken on the Map's ink by Walter McCrone (1974–1999) and

Brown and Clark (2002

). In this paper we outline and discuss the numerous arguments that are presented by Harbottle, all of which we find to be misleading or at best highly questionable.
Scaling and Testing Multiplicative Combinations in the Expectancy–Value Model of Attitudes
Authors: Ajzen Icek , Fishbein Martin
Published: September 2008

This article examines the multiplicative combination of belief strength by outcome evaluation in the expectancy–value model of attitudes. Because linear transformation of a belief strength measure results in a nonlinear transformation of its product with outcome evaluation, use of unipolar or bipolar scoring must be empirically justified. Also, the claim that the Belief × Evaluation product fails to explain significant variance in attitudes is found to be baseless. In regression analyses, the main effect of belief strength takes account of the outcome's valence, and the main effect of outcome evaluation incorporates the outcome's perceived likelihood. Simulated data showed that multiplication adds substantially to the prediction of attitudes only when belief and evaluation measures cover the full range of potential scores.
The Impact of Commuter Stress on Workplace Aggression
Authors: Hennessy Dwight A.
Published: September 2008

Immediately following their regular commute to work, participants completed questionnaires regarding state driver stress and anger during that commute. Then, immediately following completion of that work day, they completed a state version of the Workplace Aggression Scale. As state driver stress increased, the frequency of both expressed hostility and obstructionism increased (independently) during that work day, but only among male employees. In contrast, overt aggression during that work day was greatest among males who were higher in physical aggressiveness as a general trait characteristic. The present study highlights the interactive nature of traffic and workplace environments, in that negative experiences in the traffic environment may spill over for some individuals to influence nondriving events.
ORIGINAL ARTICLE: LPS Increases the Expression Levels of IL‐18, ICE and IL‐18 R in Mouse Testes
Authors: Abu Elhija Mahmoud , Lunenfeld Eitan , Huleihel Mahmoud
Published: September 2008

Problem This study examined the effect of intraperitoneal administration of lipopolysaccharide (LPS) to adult male mouse on the expression levels of interleukin‐18 (IL‐18), IL‐18 receptor (IL‐18R) and the IL‐1β converting enzyme (ICE) (IL‐18 family) in their testes and spleen (control).

Method of study Adult mice were injected (intraperitoneally; i.p.) with saline (control) or LPS (2, 20, 100 μg/mL; 100 μL/mouse). After 3 and 24 hr, testes and spleen were collected. Testicular tissue was examined for IL‐18 (by ELISA, real time PCR, and western blot analysis), IL‐18R and ICE (western blot and real time PCR analysis) and spleen tissue was examined for the IL‐18 family by real time PCR analysis. Student’s t‐test was used for statistical analysis.

Results Homogenates of mouse testes contain and express basal levels of IL‐18, ICE and IL‐18 R. The expression levels of IL‐18, ICE and IL‐18R were significantly increased 3 and 24 hr after intraperitoneal injection of LPS to mature mouse, as examined by ELISA, western blot and real time PCR analysis. However, the expression levels of IL‐18, ICE and IL‐18Rα in the spleen increased significantly only after 24 hr of LPS stimulation, as examined by real time PCR.

Conclusion Our results demonstrate that LPS increases the expression levels of the IL‐18 family in mouse testis and spleen, but the time of expression differs between the two organs. The presence of IL‐18 in the testes might be involved in the regulation of physiological and infection/inflammatory processes, and may be part of the autocrine/paracrine factors that control spermatogenesis. Further studies should be performed to confirm this possibility.
The Investigation on the Value of Repeat and Combination Test of ACA and Anti‐β2‐GPI Antibody in Women with Recurrent Spontaneous Abortion
Authors: Bao Shi Hua , Wang Xi Peng , Lin Qi De , Di Wen , Xu Liang , Ding Chuan Wei
Published: September 2008

Problem In order to investigate the value of anticardiolipin antibodies (ACA) and anti‐β2‐GPI antibodies detection in screening autoimmune type recurrent spontaneous abortion and its clinic application in antiphospholipid syndrome diagnosis, we adopt repeat combined ACA and anti‐β2‐GPI antibodies detection in this study.

Method of study Sera were collected from patients and work‐up was done for detection of ACA and anti‐β2‐GPI antibodies by enzyme‐linked immunosorbent assay (ELISA). The work‐up was done for detection of antibodies once in every 6 weeks for 14 times consecutively.

Results The repeated and combined detection of ACA and anti‐β2‐GPI antibodies detection could raise the positivity rate up to 21.8% (P < 0.05) in comparison with positive for ACA alone (14.1%), positive for anti‐β2‐GPI alone (3.1%), and concurrently positive for both ACA and anti‐β2‐GPI antibodies (4.6%). In 91 confirmed positive antiphospholipid antibodies (APA) patients, with more frequent screening for ACA and anti‐β2‐GPI antibodies, more patients with APA were found. The positive rate of five and more screenings was over 81.32%, which was statistically significant (P < 0.05), in comparison with that of four or less screenings (68.13%).

Conclusion Our data implied that it would be appropriate to take over five or more screenings of combined ACA and anti‐β2‐GPI antibodies detection in suspect patients to facilitate the positive diagnostic rate for autoimmune type RSA.
Income per Natural: Measuring Development for People Rather Than Places
Authors: Clemens Michael A. , Pritchett Lant
Published: September 2008

It is easy to learn the average income of a resident of El Salvador or Albania. But there is no systematic source of information on the average income of a Salvadoran or Albanian. We estimate a new statistic: income per natural—the mean annual income of all people born in a given country, regardless of where those people now reside. Income per natural often differs substantially from income per resident, both in its mean and in its distribution. A large part of this difference is caused by movement across borders. Indeed, for people from a number of developing countries, departing their country of birth is one of the most important sources of poverty reduction and material advancement. If economic development is that which raises human well‐being, then crossing international borders is not an alternative to economic development; it is a form of economic development.
Occupational Trajectories of Legal US Immigrants: Downgrading and Recovery
Authors: Akresh Ilana Redstone
Published: September 2008

Data from the New Immigrant Survey 2003 are examined to analyze trajectories in occupational prestige between the last job abroad and the first US job and from the first US job to the current US job for a select sample of men and women. Incorporating the first job in the United States overcomes an important limitation faced by many previous studies that were generally restricted to a comparison of the last job abroad and the US job as measured at the time of the survey. Distinctions are made between class‐of‐admission groups, since the trajectories toward labor market success vary systematically along that dimension. Consistent with a model of immigrant occupational assimilation, all preference groups show a U‐shaped adjustment pattern with, on average, initial downgrading followed by subsequent ascension. However, although all groups exhibit a similar pattern, the trough of the U is deepest for refugees, who also experience the steepest subsequent upward climb.
Growth and Development: Critique of a Credo
Authors: Daly Herman E.
Published: September 2008

With so much academic prestige and business and government experience represented on the Commission that produced the World Bank's Growth Report, issued in 2008, the reader comes to it with hopeful expectations. Unfortunately the Report is largely an apologia for globalization, the World Bank, and GDP idolatry. The Report's major failures and fallacies are identified and examined.
Convergence in Foreigners' Rights and Citizenship Policies? A Look at Japan
Authors: Surak Kristin
Published: September 2008

Citizenship laws and immigrant rights in rich, democratic countries are widely understood to be converging. Since most accounts of convergence are based on Western examples, Japan is an important test case. I distinguish three theoretical accounts of convergence: global-institutionalist, liberal-democratic, and problem-solving perspectives. I then examine trends in foreigners' rights in Japan since World War II in three domains: entrance, rights of residents, and citizenship. I find that convergence is occurring in the expansion of rights, partially in access to the territory, but not in formal citizenship. While the liberal-democratic perspective fails to account for trends, a combination of global-institutionalist and problem-solving accounts provides the most powerful analytic insight into convergence processes.
Korean Immigration Policy Changes and the Political Liberals' Dilemma
Authors: Kim Nora Hui-Jung
Published: September 2008

Recently, Korean low-skilled foreign labor policies have changed in contradictory ways. On the one hand, Korea seems to be moving in a “liberal” direction, because the government is according more rights to foreign workers. On the other hand, Korea seems to be moving in an “illiberal” direction, because the government is according ethnic Korean workers preferential treatment over other foreign workers. I explain this contradictory situation in terms of political liberals' activism. Korean political liberals' activism vis-à-vis migrant workers is two-pronged: first, to afford more rights to all migrant workers and, second, to guarantee equal treatment to all ethnic Koreans. Taken separately, each move is in line with the political liberal principle of promoting nonascriptive, universalistic, and equal treatment. Taken together, these two moves are inherently contradictory – one pushes toward ethnicizing trends and the other pushes toward de-ethnicizing trends of immigration policies. This contradiction, which I call the political liberals' dilemma, divides political liberals and weakens their overall political leverage.
Migration Differentials in Women's Market Employment: An Empirical and Multicultural Analysis
Authors: Foroutan Yaghoob
Published: September 2008

This paper examines the differences associated with the patterns and determinants of women's market employment by migration status and ethnic origin. Considering “ethnic employment” as an important issue in the immigrant labor market assimilation approach and migrants' success in the labor market as a key indication of their settlement in the host country, the results of this paper provide a basis to reassess the patterns and determinants associated with the settlement of female migrants in the multiethnic and multicultural labor market of Australia as “a particularly interesting society in which to examine how immigrant women adapt to [a] new labour market” (Evans, 1984:1063).
Little known Eucinetidae (Coleoptera: Scirtoidea) in Korea
Authors: KIM Tae‐Kyu , AHN Kee‐Jeong
Published: September 2008

The beetle family Eucinetidae, represented by Eucinetus haemorrhoidalis (Germar), is newly recorded from southern parts of the Korean Peninsula, extending its distributional range by several hundred kilometers to the south. A habitus photo and illustrations of the diagnostic characters of species are provided.
Occurrence of cotton aphids (Aphis gossypii) and lady beetles (Hamonia axyridis) on Hibiscus syriacus Linne: Are the aphids a pest of cucurbits?
Authors: KIM Yong‐Heon , KIM Hwang‐Yong , KIM Jeong‐Hwan
Published: September 2008

Populations of cotton aphid on Hibiscus syriacus increased rapidly from 17 to 24 May 2007, and then decreased as its predator, the lady beetle Hamonia axyridis, increased in number. There was a 10 day time lag between peak populations of aphids and lady beetles. The infestation of aphids on H. syriacus produced some damage, but H. syriacus recovered soon after the lady beetles arrived. Cotton aphid clones from H. syriacus were transferred to other summer host plants: to five different vegetables on two dates, and to cucumber on three dates. Apart from one case where reproduction occurred on eggplant, most H. syriacus aphid clones did not survive on the vegetables. The cotton aphid on H. syriancus was prey and a food source for H. axyridis and acted to conserve natural enemies.
External microstructure of the ambrosia beetle Platypus koryoensis (Coleoptera: Curculionidae: Platypodinae)
Authors: MOON Myung‐Jin , PARK Jong‐Gu , OH Eunsung , KIM Kyung‐Hee
Published: September 2008

Platypus koryoensis is a minute ambrosia beetle found in forests. It can cause significant economic damage to oak trees. Recently in Korea, it has been reported as a major pest of oak trees, because it causes sooty mold of oak by introducing the pathogenic fungus Raffaelea sp. In this paper, we demonstrate the fine structural aspects of the external body of the ambrosia beetle using field emission scanning electron microscopy, as a part of basic research into this pest so that strategies for its control might be developed. This beetle has a sensory system well developed to respond to both visual and chemical stimuli. Both sexes have a pair of faceted compound eyes and a pair of knobbed antennae, but simple eyes are absent. The mouthparts on its distinct snouts are effective devices for penetration and for boring holes. The mouthparts consist of the labrum, a pair of mandibles, a pair of maxillae and the labium. Both the maxillary and the labial palpi have the function of directing the food to the mouth and holding it while the mandibles chew the food. The distal ends of these palpi are flattened and have shovel‐like setae. The thorax has a particularly hard exoskeleton and hard elytra, including powerful muscles that operate both the wings and the legs. The legs are multi‐segmented and have a strong femur and tibia, including one pair of claws on the end of each tarsal segment. Characteristically, both male and female beetles have mycangial cavities for storing spores and other microorganisms, but only females have three pairs of large depressions on their dorsal thorax.
The biological characteristics of dendritic cells derived in vitro from myelogeneous leukemia cells and healthy donor cells
Authors: TONG X. M. , YAO H. P. , QIAN W. B. , ZHU L. F. , FU Z. H. , HUANG Z. L. , JIN J.
Published: September 2008

Successful adoptive immunotherapy for leukemia depends on the generation of T cells that can specifically react with malignant cells. Dendritic cells (DCs) are important antigen‐presenting cells in the development of antileukemia T‐cell responses. Mononuclear cells (MNC) were isolated from peripheral blood or bone marrow of patients with chronic myelogenous leukemia (CML), and acute myelogenous leukemia (AML). After incubation with granulocyte‐macrophage colony‐stimulating factor, interleukin (IL)‐4, and tumor necrosis factor‐α, MNC developed morphological characteristics of DCs in vitro, which were confirmed by phenotypic assay. Fluorescence in situ hybridization demonstrated the presence of fusion gene in the nuclei of representative CML or AML–M3 samples, indicating that the cells were leukemic in origin. IL‐12 levels were significantly higher in AML–DCs and CML–DCs prestimulated with phorbol 12‐myristate 13‐acetate than in the corresponding leukemic cells, but were lower than that of healthy donors. These cells were potent stimulators of lymphocyte proliferation in specific in vitro assays for DC function. However, the stimulatory abilities of allogeneic T cells in a mixed lymphocyte reaction were impaired compared with those of mature DCs derived from healthy donors, although T‐cell stimulatory effects were significantly increased in these differentiated leukemia–DCs. These results suggest that functional DCs may be derived from leukemic (AML, CML) blasts in a significant number of patients and may be capable of inducing leukemia‐specific immune responses with potentially clinically beneficial effects.
Comment on "Fire-Derived Charcoal Causes Loss of Forest Humus"
Authors: Lehmann Johannes , Sohi Saran
Published: September 2008

Wardle
et al
. (Brevia, 2 May 2008, p. 629) reported that fire-derived charcoal can promote loss of forest humus and belowground carbon (C). However, C loss from charcoal-humus mixtures can be explained not only by accelerated loss of humus but also by loss of charcoal. It is also unclear whether such loss is related to mineralization to carbon dioxide or to physical export.
Shadow Enhancers as a Source of Evolutionary Novelty
Authors: Hong Joung-Woo , Hendrix David A. , Levine Michael S.
Published: September 2008

Some developmentally important genes can be regulated via two enhancers, one located nearby and the other, a "shadow" enhancer, 10 to 20 kilobases away.
Wnt3a-Mediated Formation of Phosphatidylinositol 4,5-Bisphosphate Regulates LRP6 Phosphorylation
Authors: Pan Weijun , Choi Sun-Cheol , Wang He , Qin Yuanbo , Volpicelli-Daley Laura , Swan Laura , Lucast Louise , Khoo Cynthia , Zhang Xiaowu , Li Lin , Abrams Charles S. , Sokol Sergei Y. , Wu Dianqing
Published: September 2008

The canonical Wnt–β-catenin signaling pathway is initiated by inducing phosphorylation of one of the Wnt receptors, low-density lipoprotein receptor-related protein 6 (LRP6), at threonine residue 1479 (Thr
1479
) and serine residue 1490 (Ser
1490
). By screening a human kinase small interfering RNA library, we identified phosphatidylinositol 4-kinase type II α and phosphatidylinositol-4-phosphate 5-kinase type I (PIP5KI) as required for Wnt3a-induced LRP6 phosphorylation at Ser
1490
in mammalian cells and confirmed that these kinases are important for Wnt signaling in
Xenopus
embryos. Wnt3a stimulates the formation of phosphatidylinositol 4,5-bisphosphates [PtdIns (4,5)P
2
] through frizzled and dishevelled, the latter of which directly interacted with and activated PIP5KI. In turn, PtdIns (4,5)P
2
regulated phosphorylation of LRP6 at Thr
1479
and Ser
1490
. Therefore, our study reveals a signaling mechanism for Wnt to regulate LRP6 phosphorylation.
Laser Frequency Combs for Astronomical Observations
Authors: Steinmetz Tilo , Wilken Tobias , Araujo-Hauck Constanza , Holzwarth Ronald , Hänsch Theodor W. , Pasquini Luca , Manescau Antonio , D'Odorico Sandro , Murphy Michael T. , Kentischer Thomas , Schmidt Wolfgang , Udem Thomas
Published: September 2008

A direct measurement of the universe's expansion history could be made by observing in real time the evolution of the cosmological redshift of distant objects. However, this would require measurements of Doppler velocity drifts of ∼1 centimeter per second per year, and astronomical spectrographs have not yet been calibrated to this tolerance. We demonstrated the first use of a laser frequency comb for wavelength calibration of an astronomical telescope. Even with a simple analysis, absolute calibration is achieved with an equivalent Doppler precision of ∼9 meters per second at ∼1.5 micrometers—beyond state-of-the-art accuracy. We show that tracking complex, time-varying systematic effects in the spectrograph and detector system is a particular advantage of laser frequency comb calibration. This technique promises an effective means for modeling and removal of such systematic effects to the accuracy required by future experiments to see direct evidence of the universe's putative acceleration.
How Astronomers Have Fun (and Nearly Die Trying)
Authors: Bohannon John
Published: September 2008

In this installment, the Gonzo Scientist risks life and limb to reach the Gobi Desert in time to help rescue the sun from being swallowed by the dragon-god Rah.
Real-Time Glucose Sensors in Children and Adolescents with Type-1 Diabetes
Authors: Danne Thomas , Lange Karin , Kordonouri Olga
Published: September 2008

The increased availability of continuous glucose sensors is likely to have a significant impact on pediatric diabetes therapy and education in the future. While a recent meta-analysis of retrospective first-generation Holter-type sensors was not able to show advantages compared to self-monitoring of blood glucose levels, this review focuses on current real-time sensors. Our own experience with 23 children aged 10 (3–15) years with sensor-augmented pump therapy showed high ratings for overall satisfaction and ease of use of the system (5.8 on a 7 point Likert scale). The results of our ongoing international pediatric ONSET trial will show the impact of this technology on learning to live with diabetes by having the biofeedback of glucose excursions from the onset of diabetes. Families previously relying on self-monitoring of blood glucose need to understand the difference between estimating the absolute blood glucose value (point accuracy) and the change in blood glucose (rate accuracy), and how to take into consideration the inherent interstitial time lag. Selection of patients capable and motivated to use continuous sensors accompanied with proper age-appropriate education remain key factors for the long-term success of these new technological advances in diabetes therapy as long as closed loop systems are not available.
No Association between T222P/LGR8 Mutation and Cryptorchidism in the Moroccan Population
Authors: El Houate Brahim , Rouba Hassan , Imken Laila , Sibai Hicham , Chafik Abdelaziz , Boulouiz Redouane , Chadli Elbakkay , Hassar Mohmmed , McElreavey Ken , Barakat Abdelhamid
Published: September 2008

Background: Cryptorchidism is the most common genital anomaly in men. The INSL3/LGR8 system is involved in testicular descent via gubernacular development. INSL3 binds with high affinity to its receptor LGR8 and receptor activation is associated with cAMP signaling. Analysis of human INSL3 and LGR8 mutations confirms that some cases of cryptorchidism are caused by mutations in these genes. The T222P mutation is the only one within the LGR8 gene associated with the cryptorchidism phenotype. A strong association of the T222P mutation with cryptorchidism was found in an Italian population. Due to the same mutation being found in patients within the Mediterranean area, a possible founder effect of this mutation is supposed. Methods: We screened 109 patients with cryptorchidism and 250 controls in a Moroccan population. Results: We found that 3 of the 109 patients tested carry the T222P mutation and 4 individuals in the control group also carry the mutation. Conclusions: Our results show in fact that the same mutation is present in the Moroccan population, but an association between cryptorchidism and the T222P mutation was not found.
Clinical Description of Infants with Congenital Hypothyroidism and Iodide Organification Defects
Authors: Cavarzere Paolo , Castanet Mireille , Polak Michel , Raux-Demay Marie-Charles , Cabrol Sylvie , Carel Jean Claude , Léger Juliane , Czernichow Paul
Published: September 2008

Aims: To describe the phenotype of a large group of children with congenital hypothyroidism (CH) and iodide organification defect (IOD), suspected based on normal thyroid position and abnormal perchlorate discharge test, as first step of a project evaluating correlations between phenotypes and genotypes. Methods: 71 children born in Paris between 1980 and 2006 were included. Two groups were defined according to perchlorate discharge: total IOD (TIOD) when the release was above 90% and partial IOD (PIOD) between 10 and 90%. Comparisons between groups were performed using SPSS 14.0 for Windows. Results: The incidence of IOD over the 2003–2006 period was 1:20,660. Of the 71 children, 61 had PIOD and 10 TIOD. Compared to PIOD, TIOD was characterized by greater clinical severity. A wide spectrum of clinical features was seen in the PIOD group. Evolution showed transient hypothyroidism in 10/61 patients with PIOD and 1/10 TIOD patients. Conclusions: Severe presentation in the majority of TIOD patients suggests dysfunction of a key iodide-organification enzyme. In contrast, the variety of clinical features in PIOD group suggests that diverse mechanisms may lead to PIOD, such as delayed or reduced activity of enzymes involved in hormonogenesis or defects in iodine storage and release.
Sexual Pseudo-Precocity Caused by a Somatic Activating Mutation of the LH Receptor Preceding True Sexual Precocity
Authors: Kiepe Daniela , Richter-Unruh Annette , Autschbach Frank , Kessler Markus , Schenk Jens Peter , Bettendorf Markus
Published: September 2008

Aim: We describe the clinical features of a 6-year-old boy with sexual precocity caused by a somatic activating mutation of the luteinizing hormone (LH) receptor gene preceding gonadotropin-releasing hormone (GnRH)-dependent sexual precocity. Study Design: Genomic DNA was extracted from the right testis and from the peripheral leukocytes followed by DNA amplification and sequencing of the LH receptor gene. We described the clinical characteristics including anthropometric parameters, bone age, and endocrine evaluation when the boy presented with sexual precocity. These data were compared with the clinical and hormonal evaluation after orchiectomy preceding GnRH-dependent sexual precocity and after subsequent treatment with GnRH agonist. Results: No mutation was found in the sequence of the LH receptor gene extracted from peripheral leukocytes. Interestingly, sequencing of the tumor LH receptor gene revealed a heterozygous mutation in exon 11 encoding a replacement of Asp578His. Despite normalization of plasma testosterone, true precocious puberty was triggered within a year. Conclusions: Inmales with GnRH-independent sexual precocity the presence of small testicular Leydig cell tumorous lesions harboring a somatic mutation of the LH receptor gene should be considered. A close follow-up of affected patients should be instigated in order to monitor recurrence or subsequent true precocity.
Effects of Gender, Gonadectomy and Sex Hormones on Growth and Plasma Cholesterol Level in Rats
Authors: Lee Chong-Eon , Kang Jung-Suk , Kim Kyu-Il
Published: September 2008

Background/Aims: No studies have clearly demonstrated how sex hormones are involved in the observed gender difference in growth and plasma cholesterol levels in animals fed hypercholesterolemic diets. This study was conducted to determine the effects of gender, gonadectomy (GNX), and sex hormones on growth, plasma cholesterol and cortisol levels in Sprague-Dawley rats. Methods: In the first of two experiments, equal numbers of male and female 4-week-old rats were divided into three groups: sham-operated control, GNX, or GNX + 17α-methyltestosterone (MT). The rats were fed a hypercholesterolemic diet for 4 weeks. In a second experiment, 24 GNX females were equally divided into three groups: control, 17β-estradiol (E2), or MT. These rats were fed a normocholesterolemic diet for 3 weeks. Results: The average total plasma cholesterol level in female rats was twice that in male rats. MT administration to GNX male and GNX female rats decreased plasma cholesterol levels by 23 and 45%, respectively. Weekly intramuscular injection of E2 markedly suppressed growth while increasing plasma cortisol levels in GNX female rats. Conclusion: Testosterone decreases plasma cholesterol levels in rats fed a hypercholesterolemic diet and E2 suppresses growth of rats, inducing the secretion of hormones that increase with stress.
Vegetarian Diet Affects Genes of Oxidative Metabolism and Collagen Synthesis
Authors: Karlic Heidrun , Schuster Daniela , Varga Franz , Klindert Gerhard , Lapin Alexander , Haslberger Alexander , Handschur Michael
Published: September 2008

Background/Aim: A vegetarian diet is known to prevent a series of diseases but may influence the balance of carbohydrate and fat metabolism as well as collagen synthesis. This study compares expression patterns of relevant genes in oral mucosa of omnivores and vegetarians. Methods: Quantitative reverse transcriptase polymerase chain reaction was applied for analysis of mRNA levels from carnitine transporter OCTN2, hepatic CPT1A and nonhepatic CPT1B isoforms of carnitine palmitoyltransferase and collagen (CCOL2A1) in oral mucosa. Results: Compared with volunteers with traditional eating habits, carbohydrate consumption was significantly higher (+22%) in vegetarians. This was associated with a significant stimulation of CPT1A (+50%) and OCTN2 (+10%) and a lowered collagen synthesis (–10%). Conclusion: These novel findings provide further insight into the association of a changed fat metabolism and reduced collagen synthesis in vegetarians, which could also play a role in the aging process.
Developmental and Genetic Regulation of Human Surfactant Protein B in vivo
Authors: Hamvas Aaron , Heins Hillary B. , Guttentag Susan H. , Wegner Daniel J. , Trusgnich Michelle A. , Bennet Kate W. , Yang Ping , Carlson Christopher S. , An Ping , Cole F. Sessions
Published: September 2008

Background: Genetic and developmental disruption of surfactant protein B (SP-B) expression causes neonatal respiratory distress syndrome (RDS). Objectives: To assess developmental and genetic regulation of SP-B expression in vivo. Methods: To evaluate in vivo developmental regulation of SP-B, we used immunoblotting to compare frequency of detection of mature and pro-SP-B peptides in developmentally distinct cohorts: 24 amniotic fluid samples, unfractionated tracheal aspirates from 101 infants ≥34 weeks’ gestation with (75) and without (26) neonatal RDS, and 6 nonsmoking adults. To examine genetic regulation, we used univariate and logistic regression analyses to detect associations between common SP-B (SFTPB) genotypes and SP-B peptides in the neonatal RDS cohort. Results: We found pro-SP-B peptides in 24/24 amniotic fluid samples and in 100/101 tracheal aspirates from newborn infants but none in bronchoalveolar lavage from normal adults (0/6) (p < 0.001). We detected an association (p = 0.0011) between pro-SP-B peptides (Mr 40 and 42 kDa) and genotype of a nonsynonymous single nucleotide polymorphism at genomic position 1580 that regulates amino-terminus glycosylation. Conclusions: Pro-SP-B peptides are more common in developmentally less mature humans. Association of genotype at genomic position 1580 with pro-SP-B peptides (Mr 40 and 42 kDa) suggests genetic regulation of amino terminus glycosylation in vivo.
Can Early Echocardiographic Findings Predict Patent Ductus Arteriosus?
Authors: Kwinta Przemko , Rudziński Andrzej , Kruczek Piotr , Kordon Zbigniew , Pietrzyk Jacek Józef
Published: September 2008

Background: Prophylactic treatment with prostaglandin synthetase inhibitors (PSI) is potentially harmful. Moreover, long-term benefits of prophylactic use of indomethacin or ibuprofen are not proven. Early treatment of a high-risk population is alternative to the routine prophylactic use of PSI, but it remains unclear which newborn is at greatest risk for patent ductus arteriosus (PDA). Objective: Evaluation of the prognostic value of early echocardiographic studies with respect to PDA in later life. Methods: Sixty preterm infants with a mean birth weight of 1,087 g and mean gestational age of 28.5 weeks were included in a prospective study. Cardiac scans were performed in all newborns on entry into the study (within 12–48 h after birth) and further in case of clinical suspicion of PDA or obligatorily on the 7th and 28th days of life. There was no prophylactic or treatment use of any PSI during the study period. Newborns were divided into 2 cohorts: with significant left to right shunt requiring surgical ligation of PDA (n = 16) or without significant PDA during follow-up (control group, n = 44). Results: On entry, the mean internal diameter of the ductus arteriosus (2.6 vs. 0.91 mm/kg; p < 0.01), mean cardiac index across aortic valve (2.96 vs. 2.37 l/min/m2; p < 0.01) and early filling peak velocity (43.1 vs. 33.7; p = 0.01) were significantly higher in babies who later needed surgical ligation of PDA. There was no difference in the mean values of the other echocardiographic parameters studied. An early ductal diameter of >1.5 mm/kg predicted symptomatic PDA with a sensitivity of 94% and a specificity of 73%, and its positive predictive value equaled 57% and negative predictive value amounted to 97%. Conclusions: Early echocardiographic studies possess negative predictive value and may decrease unnecessary surgical ligation of PDA in very low birth weight infants.
Characterization and Differentiation of Iron Status in Anemic Very Low Birth Weight Infants Using a Diagnostic Nomogram
Authors: Kasper David C. , Widness John A. , Haiden Nadja , Berger Angelika , Hayde Michael , Pollak Arnold , Herkner Kurt R.
Published: September 2008

Background: In the early weeks of life, very low birth weight (VLBW) infants experience intense laboratory blood sampling leading to clinically significant anemia and the need for red blood cell transfusion. Although controversial, treatment with recombinant human erythropoietin (EPO) and iron has been recommended to stimulate erythropoiesis; optimal dosing of EPO and iron is still uncertain. Objectives: To assess the validity of a four-quadrant diagnostic plot of iron availability (ferritin index) versus iron demand for erythropoiesis (reticulocyte hemoglobin content, CHr) for differentiating iron status in anemic VLBW infants. Methods: Study subjects were enrolled in a previously reported randomized controlled trial of clinically stable VLBW infants <31 weeks’ gestation and <1,300 g at birth to receive 18 days of treatment with: group 1: oral iron; group 2: EPO + oral iron, and group 3: EPO + intravenous + oral iron. Results: At the end of treatment the ferritin index was significantly higher in both EPO groups compared to the control group. By day 18, CHr of the control group declined into the quadrant of the diagnostic plot characteristic of functional iron deficiency and anemia of chronic disease. Both EPO groups ended in the quadrants that are characteristic for latent iron deficiency and iron deficiency anemia, respectively. Conclusions: The diagnostic plot for differentiating anemia in VLBW infants may be an informative, clinically useful tool for iron status assessment under different physiologic and therapeutic erythropoietic states. Larger additional studies in difficult patient populations are needed before the clinical utility of this diagnostic procedure can be unequivocally confirmed.
Successful Treatment of Multiple Subdural Empyemata Caused by Mycoplasma hominis in a Newborn
Authors: Chong Josephine S.C. , Tseung Simon Y.T. , Lam Hugh S. , Chu Winnie C.W. , Ip Margaret , Wong Hoi T. , Zhu Cannon X.L. , Ng Pak C.
Published: September 2008

We report a case of neonatal subdural empyema caused by Mycoplasma hominis. The infant sustained severe birth-related eye injury and subsequently developed multiple subdural empyemata. This report illustrates the clinical presentation of this unusual infection and the crucial role of neurosurgical intervention and specific antimicrobial therapy for its successful management.