bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences between karyotypically normal and abnormal human embryonic stem cells
Authors: Yang S. , Lin G. , Tan Y.‐Q. , Deng L.‐Y. , Yuan D. , Lu G.‐X.
Published: April 2010

Objectives:  To compare different biological characteristics of human embryonic stem cells (HESCs) between those with normal and those with abnormal karyotype.

Materials and methods:  Culture‐adapted HESCs (chHES‐3) with abnormal karyotype were compared with karyotypically normal cells, with regard to pluripotency and differentiation capacity, ultrastructure, growth characteristics, gene expression profiles and signalling pathways.

Results:  We found a new abnormal karyotype of HESCs. We observed that chHES‐3 cells with normal and abnormal karyotypes shared similarities in expression markers of pluripotency; however, karyotypically abnormal chHES‐3 cells had a tendency for differentiation towards ectoderm lineages and were easily maintained in suboptimal culturing conditions. Abnormal chHES‐3 cells displayed relatively mature cell organelles compared to normal cells, and karyotypically abnormal chHES‐3 cells had increased survival and population growth. Genes related to cell proliferation and apoptosis were up‐regulated, but genes associated with genetic instability (p53, Rb, BRCA1) were down‐regulated in the karyotypically abnormal cells.

Conclusion:  Karyotypically abnormal chHES‐3 cells had a more developed capacity for proliferation, resistance to apoptosis and less genetic stability compared to normal chHES‐3 cells and may be an excellent model for studying and characterizing initial stages that determine transition of embryonic stem cells into cancer stem cells.
Global gene expression reveals a set of new genes involved in the modification of cells during erythroid differentiation
Authors: Da Cunha A. F. , Brugnerotto A. F. , Duarte A. S. , Lanaro C. , Costa G. G. L. , Saad S. T. O. , Costa F. F.
Published: April 2010

Objectives:  Erythroid differentiation is a dynamic process in which a pluripotent stem cell undergoes a series of developmental changes that commit it to a specific lineage. These alterations involve changes in gene expression profiles. In this study, gene expression profiles during differentiation of human erythroid cells of a normal blood donor were evaluated using SAGE.

Materials and methods:  Global gene expression was evaluated in cells collected immediately before addition of erythropoietin (0 h) and 192 and 336 h after addition of this hormone. Real‐time PCR was used to evaluate activation of differentially expressed genes.

Results:  The data indicate that global aspects of the transcriptome were similar during differentiation of the majority of the genes and that a relatively small set of genes is probably involved in modification of erythroid cells during differentiation. We have identified 93 differentially expressed genes during erythroid development, and expression of some of these was confirmed by qPCR. Various genes including EYA3, ERH, HES6, TIMELESS and TRIB3 were found to be homologous to those of Drosophila melanogaster and here are described for the first time during erythroid development. An important and unique carboxypeptidase inhibitor described in mammalians, LXN, was also identified.

Conclusions:  The results of this study amplify previously published data and may contribute to comprehension of erythroid differentiation and identification of new target genes involved in some erythroid concerning diseases.
Multiple benefits of cooperative breeding in purple‐crowned fairy‐wrens: a consequence of fidelity?
Authors: Kingma Sjouke A. , Hall Michelle L. , Arriero Elena , Peters Anne
Published: April 2010

1.Kin selection is one of the mechanisms that can explain apparent altruism by subordinate individuals in cooperatively breeding species, if subordinates boost the production of kin. We compared productivity and breeder survival in pairs with and without subordinates in a genetically monogamous cooperatively breeding bird, the purple‐crowned fairy‐wrenMalurus coronatus.

2.Additive effects of subordinate help increased productivity. Total feeding rates to the nest were increased by two or more subordinates, and fledgling production was greater in larger groups. Not all subordinates contributed to nestling feeding, and the effect of group size was greater when non‐contributors were excluded from analyses, suggesting that increased fledgling production was a direct result of help.

3.Compensatory effects of subordinate help improved breeder survival. Assisted breeders reduced their workload by 20–30%, irrespective of the number of helpers. Although re‐nesting intervals were not affected by group size, reduced breeder feeding rates resulted in improved survival and breeders in larger groups survived better.

4.Subordinates and nestlings are usually progeny of the breeding pair in this species, and benefits of cooperative breeding are very different from three congeners with extremely high levels of extra‐group paternity (EGP). In theseMalurus, fledgling production and survival of male breeders are not enhanced in larger groups. This is consistent with the expectation that kin‐selected benefits vary with relatedness, and thus levels of EGP.

5.We tested whether benefits of cooperative breeding in 37 avian species varied with levels of extra‐group mating. Both direct and phylogenetically controlled comparisons showed that improvement of (male) breeder survival and enhanced productivity are more likely when fidelity is higher, as predicted when investment of subordinates correlates with relatedness to offspring. This pattern highlights the importance of considering the genetic mating system for understanding the evolution of cooperative breeding.
Vitamin D deficiency and frailty in older Americans
Authors: Wilhelm‐Leen E. R. , Hall Y. N. , DeBoer I. H. , Chertow G. M.
Published: April 2010

Abstract.  Wilhelm‐Leen ER, Hall YN, deBoer IH, Chertow GM. (Stanford University School of Medicine; University of Washington; Stanford University School of Medicine, Palo Alto, CA, USA). Vitamin D deficiency and frailty in older Americans. J Intern Med 2010; 268: 171–180.

Objective.  To explore the relation between 25‐hydroxyvitamin D deficiency and frailty. Frailty is a multidimensional phenotype that describes declining physical function and a vulnerability to adverse outcomes in the setting of physical stress such as illness or hospitalization. Low serum concentrations of 25‐hydroxyvitamin D are known to be associated with multiple chronic diseases such as cardiovascular disease and diabetes, in addition to all cause mortality.

Design.  Using data from the Third National Health and Nutrition Survey (NHANES III), we evaluated the association between low serum 25‐hydroxyvitamin D concentration and frailty, defined according to a set of criteria derived from a definition previously described and validated.

Subjects.  Nationally representative survey of noninstitutionalized US residents collected between 1988 and 1994.

Results.  25‐Hydroxyvitamin D deficiency, defined as a serum concentration <15 ng mL−1, was associated with a 3.7‐fold increase in the odds of frailty amongst whites and a fourfold increase in the odds of frailty amongst non‐whites. This association persisted after sensitivity analyses adjusting for season of the year and latitude of residence, intended to reduce misclassification of persons as 25‐hydroxyvitamin D deficient or insufficient.

Conclusion.  Low serum 25‐hydroxyvitamin D concentrations are associated with frailty amongst older adults.
Biotic stress globally downregulates photosynthesis genes
Authors: BILGIN DAMLA D. , ZAVALA JORGE A. , ZHU JIN , CLOUGH STEVEN J. , ORT DONALD R. , DeLUCIA EVAN H.
Published: April 2010

To determine if damage to foliage by biotic agents, including arthropods, fungi, bacteria and viral pathogens, universally downregulates the expression of genes involved in photosynthesis, we compared transcriptome data from microarray experiments after twenty two different forms of biotic damage on eight different plant species. Transcript levels of photosynthesis light reaction, carbon reduction cycle and pigment synthesis genes decreased regardless of the type of biotic attack. The corresponding upregulation of genes coding for the synthesis of jasmonic acid and those involved in the responses to salicylic acid and ethylene suggest that the downregulation of photosynthesis‐related genes was part of a defence response. Analysis of the sub‐cellular targeting of co‐expressed gene clusters revealed that the transcript levels of 84% of the genes that carry a chloroplast targeting peptide sequence decreased. The majority of these downregulated genes shared common regulatory elements, such as G‐box (CACGTG), T‐box (ACTTTG) and SORLIP (GCCAC) motifs. Strong convergence in the response of transcription suggests that the universal downregulation of photosynthesis‐related gene expression is an adaptive response to biotic attack. We hypothesize that slow turnover of many photosynthetic proteins allows plants to invest resources in immediate defence needs without debilitating near term losses in photosynthetic capacity.
Passive Acquisition of Protective Antibodies Reactive with Bordetella pertussis in Newborns via Placental Transfer and Breast‐feeding
Authors: Quinello C. , Quintilio W. , Carneiro‐Sampaio M. , Palmeira P.
Published: April 2010

Although acquisition of anti‐pertussis antibodies by the newborn via placental transfer has been demonstrated, a subsequent recrudescence of pertussis infection is often observed, particularly in infants. The present study investigated the passive transfer of anti‐pertussis IgG and IgA antibodies to term newborns and their ability to neutralize bacterial pathogenicity in an in vivo experimental model using mice intracerebrally challenged with viable Bordetella pertussis. Forty paired samples of maternal/umbilical cord sera and colostrum were obtained. Anti‐pertussis antibodies were analysed by immunoenzymatic assay and by Immunoblotting. Antibody neutralizing ability was assessed through intracerebral B. pertussis challenges in mice. Anti‐pertussis IgG titres were equivalent in both maternal and newborn sera (medians = 1:225 and 1:265), with a transfer rate of 118%. The colostrum samples had variable specific IgA titres (median = 1:74). The immunoblotting assays demonstrated identical recognition profiles of paired maternal and newborn serum pools but different bacterial recognition intensities by colostrum pools. In the animal model, significant differences were always observed when the serum and colostrum samples and pools were compared with the positive control (P < 0.05). Unlike samples with lower anti‐pertussis titres, samples with high titres showed protective capacities above 50%. Pertussis‐absorbed serum and colostrum pools protected 30% of mice and purified IgG antibodies protected 65%. Both pooled and single‐sample protective abilities were correlated with antibody titres (P < 0.01). Our data demonstrated the effectiveness of anti‐pertussis antibodies in bacterial pathogenesis neutralization, emphasizing the importance of placental transfer and breast‐feeding in protecting infants against respiratory infections caused by Bordetella pertussis.
Self‐reported vision and health of indigenous Australians
Authors: Goujon Nicolas , Brown Cherylee M , Xie Jing , Arnold Anna‐Lena , Dunn Ross A , Keeffe Jill E , Taylor Hugh R
Published: April 2010

Abstract

Purpose:  To describe the self‐reported vision, history of eye disease and general health of indigenous Australian participants in the National Indigenous Eye Health Survey.

Methods:  Using a multistage cluster sampling methodology, 30 geographic areas, stratified by remoteness, were selected to provide a representative population of indigenous Australians aged 5–15 years and 40 years and over. Before an eye examination, participants completed a questionnaire about their eye health and eye care facilities consulted, satisfaction with their vision and general health.

Results:  A total of 1694 indigenous children (49.2% female, mean age 9.5 ± 2.9 years) and 1189 adults (61.0% female, mean age 53.1 ± 9.7 years) participated. Three‐quarters of adults (259/342) and 88.4% of children (129/146) wore the right distance glasses. Adults from remote areas were less likely to have refractive error (P = 0.002) as well as males versus females (P = 0.02). Similar results were found for children. Adults wearing appropriate distance glasses were as satisfied with their vision as people with normal vision who did not need glasses (P = 0.6). Both groups were more satisfied with their distance vision than people with poor presenting vision (P = 0.007). Self‐report of cataract, diabetic retinopathy, glaucoma and age‐related macular degeneration did not match with clinical findings (P < 0.001). Over 37% of adults (417/1187) and 1.3% of children (22/1691) reported having diabetes.

Conclusion:  The National Indigenous Eye Health Survey provided information to guide future planning of eye health prevention strategies for indigenous Australians. Findings indicate the importance of correcting refractive error to improve quality of life. Prevention messages should be renewed in appropriate sociocultural formats.
Retrospective study of an as required dosing regimen of intravitreal bevacizumab in neovascular age‐related macular degeneration in an Australian population
Authors: Luu Susie T , Gray Timothy , Warrier Sunil K , Patel Ilesh , Muecke James S , Casson Robert , Gilhotra Jagjit S
Published: April 2010

Abstract

Purpose:  To investigate the efficacy of intravitreal bevacizumab for the treatment of neovascular age‐related macular degeneration (AMD) using an as required dosing regimen.

Methods:  A retrospective study of 210 patients (231 eyes) with choroidal neovascularization resulting from neovasacular AMD. Patients were treated with 1.25 mg intravitreal bevacizumab at a vitreoretinal practice in Adelaide, South Australia. Patients were followed up at 2–4 weeks and then at 1‐month intervals; repeat injections were offered in the event of recurrence. Recurrence was defined as either a decrease of best‐corrected visual acuity or an increase in macular oedema, subretinal fluid or intraretinal fluid on optical coherence tomography, after complete or partial resolution in previous follow‐up visits. Patient data were collected for 12 months of follow up or until the patient's treatment was changed to ranibizumab.

Results:  Significant improvement in visual acuity and central retinal thickness was demonstrated at 1 month with an improvement of vision from logMAR equivalent 0.76 to 0.68 (P < 0.001) and a decrease of central retinal thickness from 306 µm to 244 µm (P < 0.001). This overall improvement was continued throughout the 12‐month follow‐up period; however, follow up was poor with 12‐month data available for only a small number of patients (7.8%). Ocular and systemic side‐effects were rare at 3.5% and 0.4%, respectively.

Conclusion:  Eyes with neovascular AMD treated with intravitreal bevacizumab for up to 12 months had significant functional and anatomical improvement. Further studies need to confirm the long‐term safety and efficacy of this treatment.
Strategic Orientations, Knowledge Acquisition, and Firm Performance: The Perspective of the Vendor in Cross‐Border Outsourcing
Authors: Li Yuan , Wei Zelong , Liu Yi
Published: April 2010

abstract

From the perspective of the vendors in emerging countries (VECs), this article investigates how the vendor firms in China respond to cross‐border outsourcing trends differently by examining the different effects of entrepreneurial orientation (EO) and market orientation (MO), as well as their interaction, on local vendors' acquisition of knowledge from foreign outsourcers in cross‐border outsourcing. We find that the knowledge acquisition of the vendors positively affects firm performance. Thus, the vendors need to correctly choose their strategic orientation to improve the knowledge acquisitions. Our results show the EO of the vendors has a positive effect on the knowledge acquisition, but the relationship between MO and the knowledge acquisition is an inverted U‐shape. Further, the interactive effect between EO and MO on the knowledge acquisition is positive. All these findings extend the literature in organizational learning and cross‐border outsourcing, and suggest that VECs should not only correctly choose their strategic orientation, but also pay more attention to the orientation interaction in acquiring knowledge from their partners through cross‐border outsourcing so that they can more efficiently improve their performance.
The relationship between dietary supplement use in late pregnancy and birth outcomes: a cohort study in British women
Authors: Alwan NA , Greenwood DC , Simpson NAB , McArdle HJ , Cade JE
Published: April 2010

Please cite this paper as:Alwan N, Greenwood D, Simpson N, McArdle H, Cade J. The relationship between dietary supplement use in late pregnancy and birth outcomes: a cohort study in British women. BJOG 2010;117:821–829.

Objective To examine the relationship between dietary supplement use during pregnancy and birth outcomes.

Design A prospective birth cohort.

Setting Leeds, UK.

Sample One thousand two hundred and seventy‐four pregnant women aged 18–45 years.

Methods Dietary supplement intake was ascertained using three questionnaires for the first, second and third trimesters. Dietary intake was reported in a 24‐hour dietary recall administered by a research midwife at 8–12 weeks of gestation. Information on delivery details and antenatal pregnancy complications was obtained from the hospital maternity records.

Main outcome measures Birthweight, birth centile and preterm birth.

Results Reported dietary supplement use declined from 82% of women in the first trimester of pregnancy to 22% in the second trimester and 33% in the third trimester. Folic acid was the most commonly reported supplement taken. Taking any type of daily supplement during any trimester was not significantly associated with size at birth taking into account known relevant confounders. Women taking multivitamin‐mineral supplements in the third trimester were more likely to experience preterm birth (adjusted OR = 3.4, 95% CI 1.2, 9.6,P = 0.02).

Conclusions Regular multivitamin–mineral supplement use during pregnancy, in a developed country setting, is not associated with size at birth. However, it appears to be associated with preterm birth if taken daily in the third trimester. The mechanism for this is unclear and our study’s findings need confirming by other cohorts and/or trials in developed countries.
Acupuncture for pain relief in labour: a systematic review and meta‐analysis
Authors: Cho S‐H , Lee H , Ernst E
Published: April 2010

Please cite this paper as: Cho S‐H, Lee H, Ernst E. Acupuncture for pain relief in labour: a systematic review and meta‐analysis. BJOG 2010;117:907–920.

Background  Acupuncture is frequently used for pain relief in labour, but the evidence is not clear.

Objectives  To critically evaluate the evidence for or against acupuncture for labour pain management.

Search strategy  Nineteen electronic databases, including English, Korean, Japanese, and Chinese databases, were systematically searched.

Selection criteria  All randomised controlled trials (RCTs) involving women receiving acupuncture alone, or as an adjunct to conventional analgesia, for pain relief in labour were considered.

Data collection and analysis  Pain intensity on a 100‐mm visual analogue scale (VAS; 0, no pain; 100, worst pain) and use of other analgesic methods were used as primary outcomes, and for statistical pooling. Maternal/fetal outcomes were secondary outcomes, and adverse events were also recorded. Risk of bias was assessed regarding randomisation, allocation concealment, blinding, incomplete outcome data, selective outcome reporting, and other biases.

Main results  Ten RCTs involving 2038 women were included. VAS for pain intensity data were available in seven studies; the meta‐analysis shows that acupuncture was not superior to minimal acupuncture at 1 hour (pooled mean difference −8.02; 95% CI −21.88, 5.84; I2 = 94%) and at 2 hours (−10.15; 95% CI −23.18, 2.87; I2 = 92%). Patients reported significantly reduced pain by 4 and 6% during electroacupuncture (EA) treatment at 15 (−4.09; 95% CI −8.05, −0.12) and 30 minutes (−5.94; 95% CI −9.83, −2.06), compared with placebo EA, but the effect was not maintained afterwards. Compared with no intervention, acupuncture reduced pain by only 11% for the first 30 minutes (−10.56; 95% CI −16.08, −5.03). In trials where acupuncture was compared with conventional analgesia, women receiving acupuncture required less meperidine (pooled risk ratio 0.20; 95% CI 0.12, 0.33) and other analgesic methods (0.75; 95% CI 0.66, 0.85). No acupuncture‐related adverse events were reported. Most trials did not blind participants, care providers and/or evaluators.

Author’s conclusions  The evidence from RCTs does not support the use of acupuncture for controlling labour pain. The primary studies are diverse and often flawed. Further research seems warranted.
Involvement of Src kinase in T‐type calcium channel‐dependent neuronal differentiation of NG108‐15 cells by hydrogen sulfide
Authors: Tarui Takeshi , Fukami Kazuki , Nagasawa Keita , Yoshida Shigeru , Sekiguchi Fumiko , Kawabata Atsufumi
Published: April 2010

J. Neurochem. (2010) 114, 512–519.

Hydrogen sulfide (H2S), a gasotransmitter, induces neuronal differentiation characterized by neuritogenesis and functional up‐regulation of high voltage‐activated Ca2+ channels, via activation of T‐type Ca2+ channels in NG108‐15 cells. We thus analyzed signaling mechanisms for the H2S‐evoked neuronal differentiation. NaHS, a donor for H2S, facilitated T‐type Ca2+ channel‐dependent membrane currents, an effect blocked by ascorbic acid that selectively inhibits Cav3.2 among three T‐type channel isoforms. NaHS, applied once at a high concentration (13.5 mM) or repetitively at a relatively low concentration (1.5 mM), as well as ionomycin, a Ca2+ ionophore, evoked neuritogenesis. The neuritogenesis induced by NaHS, but not by ionomycin, was abolished by mibefradil, a T‐type Ca2+ channel blocker. PP2, a Src kinase inhibitor, completely suppressed the neuritogenesis caused by NaHS or ionomycin, while it only partially blocked neuritogenesis caused by dibutyryl cAMP, a differentiation inducer. NaHS, but not dibutyryl cAMP, actually caused phosphorylation of Src, an effect blocked by 1,2‐bis(2‐aminophenoxy)ethane‐N,N,N′,N′‐tetraacetic acid acetoxymethyl, an intracellular Ca2+ chelator, mibefradil or ascorbic acid. The up‐regulation of high voltage‐activated currents in the cells treated with NaHS was also inhibited by PP2. Together, our data reveal that Src kinase participates in the T‐type Ca2+ channel‐dependent neuronal differentiation caused by NaHS/H2S in NG108‐15 cells.
The Quality of Insurance Intermediary Services—Empirical Evidence for Germany
Authors: Eckardt Martina , Räthke‐Döppner Solvig
Published: April 2010

Abstract

Competing insurance intermediaries provide heterogeneous services that are difficult for incompletely informed consumers to assess. Transaction cost economics, search theory, and principal‐agent theory provide arguments on product quality differences between exclusive agents and independent intermediaries. This article uses a sample of 927 insurance intermediaries in Germany. By performing OLS estimations, we test the impact of the different distribution channels and other factors on intermediaries’ service quality. Depending on the proxies used for service quality, we find mixed evidence for the product quality hypothesis. Service quality depends to a large extent on the information‐gathering and processing activities of the individual intermediaries, independent of the respective distribution channel.
DNA Typing for the Identification of Old Skeletal Remains from Korean War Victims*
Authors: Lee Hwan Young , Kim Na Young , Park Myung Jin , Sim Jeong Eun , Yang Woo Ick , Shin Kyoung‐Jin
Published: April 2010

Abstract:  The identification of missing casualties of the Korean War (1950–1953) has been performed using mitochondrial DNA (mtDNA) profiles, but recent advances in DNA extraction techniques and approaches using smaller amplicons have significantly increased the possibility of obtaining DNA profiles from highly degraded skeletal remains. Therefore, 21 skeletal remains of Korean War victims and 24 samples from biological relatives of the supposed victims were selected based on circumstantial evidence and/or mtDNA‐matching results and were analyzed to confirm the alleged relationship. Cumulative likelihood ratios were obtained from autosomal short tandem repeat, Y‐chromosomal STR, and mtDNA‐genotyping results, and mainly confirmed the alleged relationship with values over 105. The present analysis emphasizes the value of mini‐ and Y‐STR systems as well as an efficient DNA extraction method in DNA testing for the identification of old skeletal remains.
EXPECTATIONS AND ACCEPTABILITY OF DIABETIC AND REDUCED‐CALORIE MILK CHOCOLATES AMONG NONDIABETICS AND DIABETICS IN THE U.S.A.
Authors: MELO LAURO , CHILDS JESSICA L. , DRAKE MARYANNE , ANDRÉ BOLINI HELENA MARIA , EFRAIM PRISCILLA
Published: April 2010

Consumer expectations and acceptance of six laboratory‐developed prototypes of milk chocolate were evaluated by conjoint analysis and consumer acceptance testing with nondiabetics (n = 103 conjoint, n = 75 acceptance) and diabetics (n = 68 for conjoint, n = 71 acceptance). A conventional laboratory‐developed chocolate was produced with sucrose. Diabetic laboratory‐developed chocolates were made with a substitution of sucrose with high‐intensity sweeteners, sucralose or stevioside, and a polydextrose/lactitol blend as a bulking agent. Diabetic/reduced‐calorie milk chocolates were manufactured with an additional partial replacement of cocoa butter with whey protein concentrate. Sugar claim attribute was more important to diabetics than to nondiabetics; within this attribute, reduced sugar and sugar‐free levels were more important to diabetics, while sugar‐free was more important to nondiabetics. There was no difference for sweetener type and calorie reduction between the two groups. Differences in acceptance means (P < 0.05) for conventional, diabetic and diabetic/reduced‐calorie milk chocolates (especially for samples made with stevioside) were documented within nondiabetic and diabetic consumers and between the two consumer groups. All samples were different across nondiabetic and diabetic consumers regarding overall liking. These results demonstrate that alternative products must be developed and labeled according to the specific consumer groups they are intended to address.

PRACTICAL APPLICATIONS

This study indicated which levels of sugar claim, sweetener type and calorie reduction should be used depending on whom – nondiabetics or diabetics – diabetic/reduced‐calorie milk chocolates are being developed. Conjoint analysis is very important for development of new products because it allows for understanding which characteristics are most important prior to actual evaluation of products. Consumer testing using nondiabetic and diabetic consumers was helpful to validate the expectations determined through conjoint analysis with experimental samples.
Allele‐specific genetic interactions between Mitf and Kit affect melanocyte development
Authors: Wen Bin , Chen Yu , Li Huirong , Wang Jing , Shen Jie , Ma Aobo , Qu Jia , Bismuth Keren , Debbache Julien , Arnheiter Heinz , Hou Ling
Published: April 2010

The tyrosine kinase receptor KIT and the transcription factor MITF, each required for melanocyte development, have been shown to interact functionally both in vitro and in vivo. In vitro, KIT signaling leads to MITF phosphorylation, affecting MITF activity and stability. In vivo, the presence of the Mitf Mi‐wh allele exacerbates the spotting phenotype associated with heterozygosity for Kit mutations. Here, we show that among a series of other Mitf alleles, only the recessive Mitf mi‐bws mimics the effect of Mitf Mi‐wh on Kit. Intriguingly, Mitf mi‐bws is characterized by a splice defect that leads to a reduction of RNAs containing MITF exon 2B which encodes serine‐73, a serine phosphorylated upon KIT signaling. Nevertheless, other Mitf alleles that generally affect Mitf RNA levels, or carry a serine‐73‐to‐alanine mutation that specifically reduces exon 2B‐containing RNAs, do not show similar interactions with Kit in vivo. We conclude that the recessive Mitf mi‐bws is a complex allele that can display a semi‐dominant effect when present in a Kit‐sensitized background. We suggest that human disease variability may equally be due to complex, allele‐specific interactions between different genes.
Atomic radical abatement of organic impurities from electron beam deposited metallic structures
Authors: Wnuk Joshua D. , Gorham Justin M. , Rosenberg Samantha G. , Madey Theodore E. , Hagen Cornelis W. , Fairbrother D. Howard
Published: April 2010

Focused electron beam induced processing (FEBIP) of volatile organometallic precursors has become an effective and versatile method of fabricating metal-containing nanostructures. However, the electron stimulated decomposition process responsible for the growth of these nanostructures traps much of the organic content from the precursor’s ligand architecture, resulting in deposits composed of metal atoms embedded in an organic matrix. To improve the metallic properties of FEBIP structures, the metal content must be improved. Toward this goal, the authors have studied the effect of atomic hydrogen (AH) and atomic oxygen (AO) on gold-containing deposits formed from the electron stimulated decomposition of the FEBIP precursor, dimethyl-(acetylacetonate) gold(III), AuIII(acac)Me2. The effect of AH and AO on nanometer thick gold-containing deposits was probed at room temperature using a combination of x-ray photoelectron spectroscopy (XPS), scanning Auger electron spectroscopy, and atomic force microscopy (AFM). XPS revealed that deposits formed by electron irradiation of AuIII(acac)Me2 are only ≈10% gold, with ≈80% carbon and ≈10% oxygen. By exposing deposits to AH, all of the oxygen atoms and the majority of the carbon atoms were removed, ultimately producing a deposit composed of ≈75% gold and ≈25% carbon. In contrast, all of the carbon could be etched by exposing deposits to AO, although some gold atoms were also oxidized. However, oxygen was rapidly removed from these gold oxide species by subsequent exposure to AH, leaving behind purely metallic gold. AFM analysis revealed that during purification, removal of the organic contaminants was accompanied by a decrease in particle size, consistent with the idea that the radical treatment of the electron beam deposits produced close packed, gold particles. The results suggest that pure metallic structures can be formed by exposing metal-containing FEBIP deposits to a sequence of AO followed by AH.
Lab Experiments for the Study of Social-Ecological Systems
Authors: Janssen Marco A. , Holahan Robert , Lee Allen , Ostrom Elinor
Published: April 2010

Learning to Work Together

In group endeavors, there is often a tension between working for the greater good of the group as a whole versus working for one's own benefit. Sometimes these paths coincide and sometimes they do not; furthermore, the choices made by other group members can influence the calculation of which path to take. A pair of studies now approaches this challenge from experimental and theoretical points of view. In a forest or fishery, harvesting of wood or food needs to take into account the renewable character of the resource, as well as spatial heterogeneity.

Janssen
et al.

(p.
613
; see the Perspective by

Putterman

) show that communication among the group members is key, both to establishing a maintainable rate of harvesting, as well as enforcement via punishment of noncompliers.

Boyd
et al.

(p.
617
; see the Perspective by

Putterman

) develop a model showing that punishment, which is a costly activity, is most effectively levied when implemented with the approval of group members; that is, coordinated punishment works to the benefit of the whole, whereas individual actions do not.
The Genome of the Western Clawed Frog
Xenopus tropicalis
Authors: Hellsten Uffe , Harland Richard M. , Gilchrist Michael J. , Hendrix David , Jurka Jerzy , Kapitonov Vladimir , Ovcharenko Ivan , Putnam Nicholas H. , Shu Shengqiang , Taher Leila , Blitz Ira L. , Blumberg Bruce , Dichmann Darwin S. , Dubchak Inna , Amaya Enrique , Detter John C. , Fletcher Russell , Gerhard Daniela S. , Goodstein David , Graves Tina , Grigoriev Igor V. , Grimwood Jane , Kawashima Takeshi , Lindquist Erika , Lucas Susan M. , Mead Paul E. , Mitros Therese , Ogino Hajime , Ohta Yuko , Poliakov Alexander V. , Pollet Nicolas , Robert Jacques , Salamov Asaf , Sater Amy K. , Schmutz Jeremy , Terry Astrid , Vize Peter D. , Warren Wesley C. , Wells Dan , Wills Andrea , Wilson Richard K. , Zimmerman Lyle B. , Zorn Aaron M. , Grainger Robert , Grammer Timothy , Khokha Mustafa K. , Richardson Paul M. , Rokhsar Daniel S.
Published: April 2010

Frog Genome

The African clawed frog
Xenopus tropicalis
is the first amphibian to have its genome sequenced.

Hellsten
et al.

(p.
633
, see the cover) present an analysis of a draft assembly of the genome. The genome of the frog, which is an important model system for developmental biology, encodes over 20,000 protein-coding genes, of which more than 1700 genes have identified human disease associations. Detailed comparison of the content of protein-coding genes with other tetrapods—human and chicken—reveals extensive shared synteny, occasionally spanning entire chromosomes.
Cryogenian Glaciation and the Onset of Carbon-Isotope Decoupling
Authors: Swanson-Hysell Nicholas L. , Rose Catherine V. , Calmet Claire C. , Halverson Galen P. , Hurtgen Matthew T. , Maloof Adam C.
Published: April 2010

A Dip in the Carbon Pool

Before the diversity of animal life exploded in the Cambrian, Earth's carbon cycle was apparently strongly altered by multiple glaciation events across the globe. Carbon isotope signatures from rocks in Australia measured by

Swanson-Hysell
et al.

(p.
608
) suggest that an organic carbon reservoir formed between two global glaciations, or “snowball Earth,” several hundred million years earlier than expected. Anoxic sulfate-limited waters, caused by increased river outputs from melting glaciers, may have prohibited bacterial respiration, allowing for the accumulation of organic carbon. As organic carbon levels dropped, CO
2
was released, allowing the atmosphere to warm, preventing further glaciations, and permitting the eventual accumulation of oxygen in the oceans that led to the Cambrian explosion.
Race to Contain Plague in Quake Zone
Authors: Stone Richard
Published: April 2010

Disease specialists have launched an emergency operation in western China to avert a possible outbreak of pneumonic plague in the wake of a magnitude-6.9 earthquake in Qinghai Province.
Playing Politics Or Just a Game?
Authors: Lawler Andrew
Published: April 2010

At the Society for American Archaeology meeting, an archaeologist argued that the ball courts found throughout Mesoamerica likely began as a communal game and only later were co-opted by elites who used them for ritual and political goals.
International Multicenter Study To Assess a Panel of Reference Materials for Quantification of Simian Immunodeficiency Virus RNA in Plasma
Authors: Ham Claire , Srinivasan Priya , Thorstensson Rigmor , Verschoor Ernst , Fagrouche Zahra , Sernicola Leonardo , Ramos Artur , Titti Fausto , Almond Neil , Berry Neil
Published: April 2010

An international multicenter study was conducted to assess the performance of a panel of simian immunodeficiency virus (SIV) RNA reference materials for plasma viral load determinations. Reliable quantification was demonstrated across an ∼6 log
10
dynamic range. Availability of external reference materials will enable independent calibration of SIV plasma viral load assays.
Rearranged Genomic RNA Segments Offer a New Approach to the Reverse Genetics of Rotaviruses
Authors: Troupin Cécile , Dehée Axelle , Schnuriger Aurélie , Vende Patrice , Poncet Didier , Garbarg-Chenon Antoine
Published: April 2010

Group A rotaviruses (RV), members of the
Reoviridae
family, are a major cause of infantile acute gastroenteritis. The RV genome consists of 11 double-stranded RNA segments. In some cases, an RNA segment is replaced by a rearranged RNA segment, which is derived from its standard counterpart by partial sequence duplication. We report here a reverse genetics system for RV based on the preferential packaging of rearranged RNA segments. Using this system, wild-type or
in vitro
-engineered forms of rearranged segment 7 from a human rotavirus (encoding the NSP3 protein), derived from cloned cDNAs and transcribed in the cytoplasm of COS-7 cells with the help of T7 RNA polymerase, replaced the wild-type segment 7 of a bovine helper virus (strain RF). Recombinant RF viruses (i.e., engineered monoreassortant RF viruses) containing an exogenous rearranged RNA were recovered by propagating the viral progeny in MA-104 cells, with no need for additional selective pressure. Our findings offer the possibility to extend RV reverse genetics to segments encoding nonstructural or structural proteins for which no potent selective tools, such as neutralizing antibodies, are available. In addition, the system described here is the first to enable the introduction of a mutated gene expressing a modified nonstructural protein into an infectious RV. This reverse genetics system offers new perspectives for investigating RV protein functions and developing recombinant live RV vaccines containing specific changes targeted for attenuation.
REMARKS ON EXISTENCE OF PROPER ACTION FOR REDUCIBLE GAUGE THEORIES
Authors: BATALIN IGOR A. , BERING KLAUS
Published: April 2010

In the field–antifield formalism, we review existence and uniqueness proofs for the proper action in the reducible case. We give two new existence proofs based on two resolution degrees called "reduced antifield number" and "shifted antifield number," respectively. In particular, we show that for every choice of gauge generators and their higher stage counterparts, there exists a proper action that implements them at the quadratic order in the auxiliary variables.
WILSON LOOP IN 2D NONCOMMUTATIVE GAUGE THEORIES
Authors: VALTANCOLI P.
Published: April 2010

We reconsider the perturbative expansion of the Wilson loop in 2D noncommutative gauge theories, using an improved integration method. For the class of maximally crossed diagrams in the θ → ∞ limit we find an intriguing formula, easily generalizable to all orders in perturbation theory.
Extrastriate Area MST and Parietal Area VIP Similarly Represent Forward Headings
Authors: Maciokas James B. , Britten Kenneth H.
Published: April 2010

Many studies have documented the involvement of medial superior temporal extrastriate area (MST) in the perception of heading based on optic flow information. Furthermore, both heading perception and the responses of MST neurons are relatively stable in the presence of eye movements that distort the retinal flow information on which perception is based. Area VIP in the posterior parietal cortex also contains a robust representation of optic flow cues for heading. However, the studies in the two areas were frequently conducted using different stimuli, making quantitative comparison difficult. To remedy this, we studied MST using a family of random dot heading stimuli that we have previously used in the study of VIP. These stimuli simulate observer translation through a three-dimensional cloud of points, and a range of forward headings was presented both with and without horizontal smooth pursuit eye movements. We found that MST neurons, like VIP neurons, respond robustly to these stimuli and partially compensate for the presence of pursuit. Quantitative comparison of the responses revealed no substantial difference between the heading responses of MST and VIP neurons or in their degree of pursuit tolerance.
Strengthening Intersectoral Collaboration for Primary Health Care in Developing Countries: Can the Health Sector Play Broader Roles?
Authors: Adeleye Omokhoa Adedayo , Ofili Antoinette Ngozi
Published: April 2010

Many strategic challenges impeding the success of primary health care are rooted in weak strategic inputs, including intersectoral collaboration. Some encouraging evidence from programmes, projects, and studies suggests that intersectoral collaboration is feasible and useful. The strategy has the potential to fast-track the attainment of Millenium Development Goals. However, the strategy is not commonly utilised in developing countries. The health sector expects inputs from other sectors which may not necessarily subscribe to a shared responsibility for health improvement, whereas the public expects ‘‘health’’ from the health sector. Yet, the health sector rarely takes on initiatives in that direction. The sector is challenged to mobilise all stakeholders for intersectoral collaboration through advocacy and programming. Pilot projects are advised in order to allow for cumulative experience, incremental lessons and more supportive evidence.
Intrahepatic Sarcomatoid Cholangiocarcinoma
Authors: Malhotra Shalini , Wood Joanna , Mansy Talal , Singh Rajeev , Zaitoun Abed , Madhusudan Srinivasan
Published: April 2010

Intrahepatic sarcomatoid cholangiocarcinoma is a rare but an aggressive variant of cholangiocarcinoma with a very poor prognosis. We report the first caucasian patient who presented with a rapidly enlarging liver mass requiring hepatic resection. Detailed histopathological analyses including immunohistochemistry and electron microscopy confirmed sarcomatoid cholangiocarcinoma. The patient had early onset disease recurrence within 5 weeks of surgery. Here we demonstrate that combination chemotherapy with gemcitabine and cisplatin is a potential treatment option in patients with advanced sarcomatous cholangiocarcinoma. The patient achieved sustained partial remission with combination chemotherapy and remains alive and well more than 29 months since initial surgery.
Nitric oxide derivatives and soluble plasma selectins in patients with myeloproliferative neoplasms
Authors: Cella Giuseppe , Marchetti Marina , Vianello Fabrizio , Panova-Noeva Marina , Vignoli Alfonso , Russo Laura , Barbui Tiziano , Falanga Anna
Published: April 2010

Essential thrombocythaemia (ET) and polycythaemia vera (PV) are characterised by a high incidence of thrombotic complications due to highshear stress of the vessel wall, blood hyperviscosity and hypoxaemia, all factors responsible for chronic endothelial dysfunction and platelet and leukocyte activation. We evaluated the activation status of vascular cells in 18 consecutive ET and 14 PV patients by measuring the plasma levels of the nitric oxide derivatives (NOX) (i.e. nitrites and nitrates) and of soluble selectins of platelet (P-selectin), endothelial cell (P-selectin and E-selectin) and leukocyte (L-selectin) origin. The effect of hydroxyurea (HU) therapy on these parameters was also investigated. NOX were significantly (p<0.01) increased in ET patients treated with HU (11.5 ± 2.6 nM) compared to non-HU treated ET (1.41 ± 0.3 nM) and to controls (4.78 ± 2.49 nM). Multivariate analysis confirmed HU therapy as an independent predictor of higher NOX levels in ET. In addition, NOX significantly correlated with haematocrit. Plasma P-selectin was significantly elevated in ET (350 ± 40 ng/106 platelets) and PV (482 ± 53 ng/106 platelets) patients compared to controls (120 ± 8 ng/106 platelets). In PV, also E-selectin (23.8 ± 4.2 ng/ml) was significantly increased compared to controls (11.2 ± 1.1 ng/ml; p<0.01). P-selectin was significantly correlated to platelet (R=0.33; p=0.01) and leukocyte count (R=0.6; p=0.000), while E-selectin (R=0.34; p=.014) and sL-selectin (R=0.3; p=0.03) were correlated with leukocyte count only. In the multivariate analysis, NOX predicted increased levels of E-selectin in ET, but not in PV patients. Our data demonstrate that ET and PV are characterised by an altered pattern of soluble selectins and NOX. HU-mediated increase of NOMX levels could represent an additional antithrombotic mechanism of this drug.
Gelatinase B (MMP-9) deficiency does not affect murine adipose tissue development
Authors: Van Hul Matthias , Piccard Heléne , Lijnen H. Roger
Published: April 2010

This study was performed to follow up on the observation that gelatinase A (MMP-2) deficiency impairs adipose tissue development in mice. The aim was to evaluate the role of its functional homologue gelatinase B (MMP-9) in adipose tissue growth. MMP-9 antigen levels were determined in lean and in obese women before and after weight loss. MMP-9-deficient mice and wild-type littermates (genetic background 50% 129sv : 50% CDI or 99.975% C57Bl/6, ten generations backcrossed into C57Bl/6 background) were kept on a high-fat diet (HFD) for 15 weeks. Subcutaneous and gonadal fat pads were analysed in terms of weight and size/density of adipocytes and blood vessels. Obese women had higher MMP-9 serum levels than lean controls (383 ± 29 vs. 304 ± 27 ng/ml, p = 0.02); after weight reduction MMP-9 levels dropped to 334 ± 17 ng/ml (p = 0.1 vs. obese). However, MMP-9-deficient and littermate wild-type mice kept on HFD were indistinguishable in terms of body and fat weight. No effect of MMP-9 deficiency was observed on size or density of adipocytes or blood vessels in subcutaneous or gonadal fat depots. Similar observations were made when mice were kept on normal chow. In conclusion, in lean and obese women, body mass index correlates positively with MMP-9 serum levels (p < 0.0001). However, MMP-9 does not seem to play a major role in adipose tissue development in murine models of diet-induced obesity.
Implications of the UN Convention against Corruption for International Organizations: Oversight, Due Process, and Immunities Issues
Authors: Trebilcock Anne
Published: April 2010

While public international organizations share the aspirations and values behind the United Nations Convention against Corruption (UNCAC), the way in which this instrument is being followed up may pose some practical challenges for them. The Convention mentions such organizations and their officials, but in the context of an instrument whose logic is overwhelmingly directed towards States. In the course of UNCAC implementation review, some unfortunate confusion has arisen between administrative justice and criminal jurisdiction, and around the privileges and immunities regime for international organizations. At the same time, follow-up to the Convention may offer new opportunities for such organizations to strengthen their alignment of responsibility, authority and accountability through so far underutilized means of coordination and cooperation. Strengthening accountability mechanisms and respect for due process – two components of the Global Administrative Law approach – offer the best prospects for enhancing international organizations' efforts against corruption. An exaggerated focus on transparency, on the other hand, could run counter to effective measures to combat it.
Accountability and Independence of International Election Observers
Authors: van Aaken Anne , Chambers Richard
Published: April 2010

International election monitoring has become ever more important in the national as well as the international context. Plenty of (regional) International Organizations (and NGOs) send Election Observers Missions (EOMs) to countries in order to assess the quality of their democratic process and elections. Whereas the influence of EOMs is largely undisputed, their independence, impartiality and accountability have been less discussed. This paper describes the legal set-up of EOMs in order to assess their independence and accountability. It also uses accountability mechanisms as discussed in international law scholarship (ILA Report and the Global Administrative Law project) in order to analyze the accountability mechanisms currently in place for EOMs.