bluuebunny/crossref_metadata_2025 huggingface dataset:
RETRACTED: Wnt-5a signaling restores tamoxifen sensitivity in estrogen receptor-negative breast cancer cells
Authors: Ford Caroline E. , Ekström Elin J. , Andersson Tommy
Published: February 2009

One third of all breast cancers are estrogen receptor alpha (ERα) negative, carry a poor overall prognosis, and do not respond well to currently available endocrine therapies. New treatment strategies are therefore required. Loss of Wnt-5a has previously been correlated with loss of ERα in clinical breast cancer samples, and we sought to investigate this association further. Three breast cancer cell lines (MDA-MB-231, MDA-MB-468, and 4T1) lacking expression of ERα and Wnt-5a, and one breast cancer cell line (T47D) expressing both proteins were used in this study. Wnt-5a signaling was generated in ERα-negative cell lines via stimulation with either recombinant Wnt-5a protein or a Wnt-5a-derived hexapeptide (Foxy-5) possessing Wnt-5a signaling properties. ERα expression was restored at both mRNA and protein level, after treatment with recombinant Wnt-5a or Foxy-5. This restoration of expression occurred in parallel with a reduction in methylation of the ERα promoter. Up-regulated ERα could be activated, initiate transcription of progesterone receptor and pS2, and activate an estrogen response element reporter construct. Significantly, breast cancer cells re-expressing ERα responded to treatment with the selective estrogen receptor modulator tamoxifen, as measured by induction of apoptosis and cell growth inhibition. Finally, Foxy-5 also increased ERα expression in an in vivo model of ERα-negative breast cancer. This represents the first evidence that Wnt-5a signaling acts to re-establish ERα expression in ERα-negative breast cancer cells. Our data suggest that combinatorial therapy with Foxy-5 and tamoxifen should be considered as a future treatment possibility for ERα-negative breast cancer patients.
Aberrant E2F activation by polyglutamine expansion of androgen receptor in SBMA neurotoxicity
Authors: Suzuki Eriko , Zhao Yue , Ito Saya , Sawatsubashi Shun , Murata Takuya , Furutani Takashi , Shirode Yuko , Yamagata Kaoru , Tanabe Masahiko , Kimura Shuhei , Ueda Takashi , Fujiyama Sally , Lim Jinseon , Matsukawa Hiroyuki , Kouzmenko Alexander P. , Aigaki Toshiro , Tabata Tetsuya , Takeyama Ken-ichi , Kato Shigeaki
Published: February 2009

Spinal and bulbar muscular atrophy (SBMA) is a neurodegenerative disorder caused by a polyglutamine repeat (polyQ) expansion within the human androgen receptor (AR). Unlike other neurodegenerative diseases caused by abnormal polyQ expansion, the onset of SBMA depends on androgen binding to mutant human polyQ-AR proteins. This is also observed in
Drosophila
eyes ectopically expressing the polyQ-AR mutants. We have genetically screened mediators of androgen-induced neurodegeneration caused by polyQ-AR mutants in
Drosophila
eyes. We identified Rbf (Retinoblastoma-family protein), the
Drosophila
homologue of human Rb (Retinoblastoma protein), as a neuroprotective factor. Androgen-dependent association of Rbf or Rb with AR was remarkably potentiated by aberrant polyQ expansion. Such potentiated Rb association appeared to attenuate recruitment of histone deacetyltransferase 1 (HDAC1), a corepressor of E2F function. Either overexpression of Rbf or E2F deficiency in fly eyes reduced the neurotoxicity of the polyQ-AR mutants. Induction of E2F function by polyQ-AR-bound androgen was suppressed by Rb in human neuroblastoma cells. We conclude that abnormal expansion of polyQ may potentiate innate androgen-dependent association of AR with Rb. This appears to lead to androgen-dependent onset of SBMA through aberrant E2F transactivation caused by suppressed histone deacetylation.
Lipocalin 2 promotes breast cancer progression
Authors: Yang Jiang , Bielenberg Diane R. , Rodig Scott J. , Doiron Robert , Clifton Matthew C. , Kung Andrew L. , Strong Roland K. , Zurakowski David , Moses Marsha A.
Published: February 2009

Here, we report that lipocalin 2 (Lcn2) promotes breast cancer progression, and we identify the mechanisms underlying this function. We first found that Lcn2 levels were consistently associated with invasive breast cancer in human tissue and urine samples. To investigate the function of Lcn2 in breast cancer progression, Lcn2 was overexpressed in human breast cancer cells and was found to up-regulate mesenchymal markers, including vimentin and fibronectin, down-regulate the epithelial marker E-cadherin, and significantly increase cell motility and invasiveness. These changes in marker expression and cell motility are hallmarks of an epithelial to mesenchymal transition (EMT). In contrast, Lcn2 silencing in aggressive breast cancer cells inhibited cell migration and the mesenchymal phenotype. Furthermore, reduced expression of estrogen receptor (ER) α and increased expression of the key EMT transcription factor Slug were observed with Lcn2 expression. Overexpression of ERα in Lcn2-expressing cells reversed the EMT and reduced Slug expression, suggesting that ERα negatively regulates Lcn2-induced EMT. Finally, orthotopic
s
tudies demonstrated that Lcn2-expressing breast tumors displayed a poorly differentiated phenotype and showed increased local tumor invasion and lymph node metastasis. Taken together, these in vitro, in vivo, and human studies demonstrate that Lcn2 promotes breast cancer progression by inducing EMT through the ERα/Slug axis and may be a useful biomarker of breast cancer.
The outbreak of cooperation among success-driven individuals under noisy conditions
Authors: Helbing Dirk , Yu Wenjian
Published: February 2009

According to Thomas Hobbes'
Leviathan
[1651; 2008 (Touchstone, New York), English Ed], “the life of man [is] solitary, poor, nasty, brutish, and short,” and it would need powerful social institutions to establish social order. In reality, however, social cooperation can also arise spontaneously, based on local interactions rather than centralized control. The self-organization of cooperative behavior is particularly puzzling for social dilemmas related to sharing natural resources or creating common goods. Such situations are often described by the prisoner's dilemma. Here, we report the sudden outbreak of predominant cooperation in a noisy world dominated by selfishness and defection, when individuals imitate superior strategies and show success-driven migration. In our model, individuals are unrelated, and do not inherit behavioral traits. They defect or cooperate selfishly when the opportunity arises, and they do not know how often they will interact or have interacted with someone else. Moreover, our individuals have no reputation mechanism to form friendship networks, nor do they have the option of voluntary interaction or costly punishment. Therefore, the outbreak of prevailing cooperation, when directed motion is integrated in a game-theoretical model, is remarkable, particularly when random strategy mutations and random relocations challenge the formation and survival of cooperative clusters. Our results suggest that mobility is significant for the evolution of social order, and essential for its stabilization and maintenance.
Aromatic D-amino acids act as chemoattractant factors for human leukocytes through a G protein-coupled receptor, GPR109B
Authors: Irukayama-Tomobe Yoko , Tanaka Hirokazu , Yokomizo Takehiko , Hashidate-Yoshida Tomomi , Yanagisawa Masashi , Sakurai Takeshi
Published: February 2009

GPR109B (HM74) is a putative G protein-coupled receptor (GPCR) whose cognate ligands have yet to be characterized. GPR109B shows a high degree of sequence similarity to GPR109A, another GPCR that was identified as a high-affinity nicotinic acid (niacin) receptor. However, the affinity of nicotinic acid to GPR109B is very low. In this study, we found that certain aromatic D-amino acids, including D-phenylalanine, D-tryptophan, and the metabolite of the latter, D-kynurenine, decreased the activity of adenylate cyclase in cells transfected with
GPR109B
cDNA through activation of pertussis toxin (PTX)-sensitive G proteins. These D-amino acids also elicited a transient rise of intracellular Ca
2+
level in cells expressing GPR109B in a PTX-sensitive manner. In contrast, these D-amino acids did not show any effects on cells expressing GPR109A. We found that the
GPR109B
mRNA is abundantly expressed in human neutrophils. D-phenylalanine and D-tryptophan induced a transient increase of intracellular Ca
2+
level and a reduction of cAMP levels in human neutrophils. Furthermore, knockdown of
GPR109B
by RNA interference inhibited the D-amino acids-induced decrease of cellular cAMP levels in human neutrophils. These D-amino acids induced chemotactic activity of freshly prepared human neutrophils. We also found that D-phenylalanine and D-tryptophan induced chemotactic responses in Jurkat cells transfected with the
GPR109B
cDNA but not in mock-transfected Jurkat cells. These results suggest that these aromatic D-amino acids elicit a chemotactic response in human neutrophils via activation of GPR109B.
Wnt/β-Catenin and noncanonical Wnt signaling interact in tissue evagination in the simple eumetazoan
Hydra
Authors: Philipp Isabelle , Aufschnaiter Roland , Özbek Suat , Pontasch Stefanie , Jenewein Marcell , Watanabe Hiroshi , Rentzsch Fabian , Holstein Thomas W. , Hobmayer Bert
Published: February 2009

In and evaginations of 2D cell sheets are major shape generating processes in animal development. They result from directed movement and intercalation of polarized cells associated with cell shape changes. Work on several bilaterian model organisms has emphasized the role of noncanonical Wnt signaling in cell polarization and movement. However, the molecular processes responsible for generating tissue and body shape in ancestral, prebilaterian animals are unknown. We show that noncanonical Wnt signaling acts in mass tissue movements during bud and tentacle evagination and regeneration in the cnidarian polyp
Hydra
. The
wnt5
,
wnt8
,
frizzled2
(
fz2
), and
dishevelled
-expressing cell clusters define the positions, where bud and tentacle evaginations are initiated;
wnt8
,
fz2
, and
dishevelled
remain up-regulated in those epithelial cells, undergoing cell shape changes during the entire evagination process. Downstream of
wnt
and
dsh
expression, JNK activity is required for the evagination process. Multiple ectopic
wnt5
,
wnt8
,
fz2
, and
dishevelled
-expressing centers and the subsequent evagination of ectopic tentacles are induced throughout the body column by activation of Wnt/β-Catenin signaling. Our results indicate that integration of axial patterning and tissue morphogenesis by the coordinated action of canonical and noncanonical Wnt pathways was crucial for the evolution of eumetazoan body plans.
Epstein-Barr virus nuclear protein EBNA3C residues critical for maintaining lymphoblastoid cell growth
Authors: Maruo Seiji , Wu Yi , Ito Taku , Kanda Teru , Kieff Elliott D. , Takada Kenzo
Published: February 2009

Epstein-Barr virus (EBV) nuclear antigen 3C (EBNA3C) is essential for efficient conversion of primary human B lymphocytes to lymphoblastoid cell lines (LCLs) and for continued LCL growth. We used a transcomplementation assay in the context of LCLs transformed by an EBV with a conditional EBNA3C to identify the EBNA3C amino acids (aa) necessary for maintaining LCL growth. Surprisingly, we found that most EBNA3C aa were essential for continued LCL growth. Only EBNA3C mutants deleted for residues within aa 507–515, 516–620, 637–675, or 676–727 maintained full LCL growth, and EBNA3C mutants deleted for residues within aa 728–732 or 910–992 maintained slow LCL growth. In contrast, EBNA3C lacking aa 180–231, which mediate RBP-Jκ association and are necessary for EBNA3C abrogation of EBNA2-induced transcription through RBP-Jκ, could not support LCL growth. Furthermore, 2 EBNA3C alanine substitution mutants within aa 180–231, which were wild-type (wt) in abrogating EBNA2-mediated transcription through RBP-Jκ, maintained LCL growth, and 2 alanine substitution mutants within aa 180–231, which were null in abrogating EBNA2-mediated transcription through RBP-Jκ, did not maintain LCL growth. This indicates that EBNA3C regulation of transcription through RBP-Jκ is critical to maintaining LCL growth. Several other EBNA3C functions also are critical for LCL growth, because EBNA3C mutants deleted for residues within aa 130–159, 251–506, or 733–909 were wt in abrogating transcription through RBP-Jκ and expression level, but did not maintain LCL growth.
Adjuvanted H5N1 vaccine induces early CD4+T cell response that predicts long-term persistence of protective antibody levels
Authors: Galli Grazia , Medini Duccio , Borgogni Erica , Zedda Luisanna , Bardelli Monia , Malzone Carmine , Nuti Sandra , Tavarini Simona , Sammicheli Chiara , Hilbert Anne K. , Brauer Volker , Banzhoff Angelika , Rappuoli Rino , Del Giudice Giuseppe , Castellino Flora
Published: February 2009

Immune responses to vaccination are tested in clinical trials. This process usually requires years especially when immune memory and persistence are analyzed. Markers able to quickly predict the immune response would be very useful, particularly when dealing with emerging diseases that require a rapid response, such as avian influenza. To address this question we vaccinated healthy adults at days 1, 22, and 202 with plain or MF59-adjuvanted H5N1 subunit vaccines and tested both cell-mediated and antibody responses up to day 382. Only the MF59-H5N1 vaccine induced high titers of neutralizing antibodies, a large pool of memory H5N1-specific B lymphocytes, and H5-CD4+T cells broadly reactive with drifted H5. The CD4+response was dominated by IL-2+IFN-γ−IL-13−T cells. Remarkably, a 3-fold increase in the frequency of virus-specific total CD4+T cells, measurable after 1 dose, accurately predicted the rise of neutralizing antibodies after booster immunization and their maintenance 6 months later. We suggest that CD4+T cell priming might be used as an early predictor of the immunogenicity of prepandemic vaccines.
Glycogen synthase kinase 3β missplicing contributes to leukemia stem cell generation
Authors: Abrahamsson Annelie E. , Geron Ifat , Gotlib Jason , Dao Kim-Hien T. , Barroga Charlene F. , Newton Isabel G. , Giles Francis J. , Durocher Jeffrey , Creusot Remi S. , Karimi Mobin , Jones Carol , Zehnder James L. , Keating Armand , Negrin Robert S. , Weissman Irving L. , Jamieson Catriona H. M.
Published: February 2009

Recent evidence suggests that a rare population of self-renewing cancer stem cells (CSC) is responsible for cancer progression and therapeutic resistance. Chronic myeloid leukemia (CML) represents an important paradigm for understanding the genetic and epigenetic events involved in CSC production. CML progresses from a chronic phase (CP) in hematopoietic stem cells (HSC) that harbor the BCR-ABL translocation, to blast crisis (BC), characterized by aberrant activation of β-catenin within granulocyte-macrophage progenitors (GMP). A major barrier to predicting and inhibiting blast crisis transformation has been the identification of mechanisms driving β-catenin activation. Here we show that BC CML myeloid progenitors, in particular GMP, serially transplant leukemia in immunocompromised mice and thus are enriched for leukemia stem cells (LSC). Notably, cDNA sequencing of Wnt/β-catenin pathway regulatory genes, including adenomatous polyposis coli, GSK3β, axin 1, β-catenin, lymphoid enhancer factor-1, cyclin D1, and c-myc, revealed a novel in-frame splice deletion of the GSK3β kinase domain in the GMP of BC samples that was not detectable by sequencing in blasts or normal progenitors. Moreover, BC CML progenitors with misspliced GSK3β have enhanced β-catenin expression as well as serial engraftment potential while reintroduction of full-length GSK3β reduces both in vitro replating and leukemic engraftment. We propose that CP CML is initiated by BCR-ABL expression in an HSC clone but that progression to BC may include missplicing of GSK3β in GMP LSC, enabling unphosphorylated β-catenin to participate in LSC self-renewal. Missplicing of GSK3β represents a unique mechanism for the emergence of BC CML LSC and might provide a novel diagnostic and therapeutic target.
Lumbopelvic pain associated with catastrophizing and fear‐avoidance beliefs in early pregnancy
Authors: OLSSON CHRISTINA , BUER NINA , HOLM KERSTIN , NILSSON‐WIKMAR LENA
Published: February 2009

Objective. To examine and compare levels of catastrophizing, fear‐avoidance beliefs, physical ability, and health‐related quality of life in women with and without lumbopelvic pain (LP and NLP) in early pregnancy. Design. A cross‐sectional study of early pregnancy. Setting. Five midwife clinics, one in the center, two in the outskirts of Stockholm, and two in a medium‐sized town. Population. Three hundred and twenty‐four women in the 19th–21st week of pregnancy. Methods. Questionnaires. Main outcome measures. The Pain Catastrophizing Scale of exaggerated negative thoughts about pain experiences, the Fear‐Avoidance Beliefs Questionnaire of beliefs about how physical activity and work affect back pain, the Disability Rating Index of physical ability, and the Nottingham Health Profile to assess health‐related quality of life. Results. Two groups were defined: LP (n = 141) and NLP (n = 183). The Mann–Whitney U‐test was used for comparisons. Pregnant women with LP had significantly (p<0.05) higher levels of exaggerated negative thoughts and fear‐avoidance beliefs. They also had lower physical ability and health‐related quality of life compared to women in the NLP group. Conclusions. It is important to consider exaggerated negative thoughts about pain experiences and fear‐avoidance beliefs when treating women with LP during pregnancy and to be aware of the great impact lumbopelvic pain has on women's lives during early pregnancy.
Preoperative levels of plasma micronutrients are related to endometrial cancer risk
Authors: JEONG NAN‐HEE , SONG EUN‐SEOP , LEE JONG‐MIN , LEE KWANG‐BEOM , KIM MI‐KYUNG , YUN YOUNG‐MI , LEE JAE‐KWAN , SON SUNG‐KYONG , LEE JUNG‐PIL , KIM JAE‐HOON , HUR SOO‐YOUNG , KWON YONG‐IL
Published: February 2009

Objective. To examine the relation between the plasma concentration of antioxidant micronutrients and endometrial cancer risk in Korean women. Design. Hospital‐based case–control study. Setting. Seven tertiary medical institutes in Korea. Population. Incidence of 28 endometrial cancer cases were identified and 140 age‐matched controls selected for the same period.Methods. Preoperative plasma concentrations of β‐carotene, lycopene, zeaxanthin plus lutein, retinol, α‐tocopherol, and γ‐tocopherol were measured by reverse‐phase, gradient high‐pressure liquid chromatography. Conditional logistic regression was used to evaluate micronutrient effect after adjustment for body mass index (BMI), menopause, parity, oral contraceptive use, smoking status, and alcohol consumption status.Main outcome measures. Effect of micronutrients on endometrial cancer risk.Results. The mean concentration of plasma β‐carotene (p = 0.001), lycopene (p = 0.008), zeaxanthin plus lutein (p = 0.031), retinol (p = 0.048), and γ‐tocopherol (p = 0.046) were significantly lower in endometrial cancer patients than in controls. Plasma levels of β‐carotene (p for trend = 0.0007) and lycopene (p for trend = 0.007) were inversely associated with endometrial cancer risk across tertiles. Women in the highest tertile of plasma β‐carotene and lycopene had a 0.12‐fold (95% confidence intervals (CIs) 0.03–0.48) and 0.15‐fold (95% CIs 0.04–0.61) decreased risk of endometrial cancer compared to women in the lowest tertile, respectively. Other micronutrients such as zeaxanthin plus lutein (p for trend = 0.142), retinol (p for trend = 0.108), α‐tocopherol (p for trend = 0.322), and γ‐tocopherol (p for trend = 0.087) showed no association with endometrial cancer risk.Conclusions. Plasma levels of β‐carotene and lycopene are inversely associated with the risk of endometrial cancer in Korean women.
Clinical profile of menopausal insomniac women referred to sleep laboratory
Authors: HACHUL HELENA , BRANDÃO LETÍCIA DE C. , BITTENCOURT LIA R.A. , D'ALMEIDA VÂNIA , ANDERSEN MONICA L. , BARACAT EDMUND C. , TUFIK SERGIO
Published: February 2009

Objective. The primary purpose of this study was to assess the overall clinical profile of menopausal women complaining of insomnia who were referred to a sleep laboratory. Methods. A total of 206 menopausal women who had complaints related to insomnia were interviewed. Each participant completed a questionnaire in order to obtain data on general health, menopausal status, medications, and sleep patterns. Results. The mean age of the participants was 55.9 years. Clinical profiles revealed that the most prevalent health problems were systemic arterial hypertension (33.9%) and osteoporosis (19%), though there was no association between insomnia and incidence of chronic disease. Our data demonstrate an overall prevalence of insomnia of 4–5 times a week in 62% of the women, with 68.9% complaining of hot flashes. However, there was no association between hot flashes and frequency of insomnia across the menopausal transition period. Only 7% of women had already undergone polysomnography. Less than 5% of the participants were undergoing treatment for menopause, while 8% were taking benzodiazepines for sleep problems. Conclusions. This study provides evidence that insomnia in postmenopausal women was not associated with incidence of chronic disease. In addition, the majority of the participants were not undergoing treatment for menopause or for sleep disturbance.
Ultrasound assessment of the prognosis in triplet pregnancies
Authors: GUILHERME ROMAIN , LE RAY CAMILLE , VUILLARD EDITH , GAREL CATHERINE , DELEZOIDE ANNE‐LISE , OURY JEAN‐FRANÇOIS , LUTON DOMINIQUE
Published: February 2009

Objective. To assess the diagnostic accuracy and show the prognostic influence of different ultrasonographic criteria in triplet pregnancies(TP). Design. Retrospective study. Setting. Tertiary care center in France. Population. Fifty‐one consecutive TP in which at least one of the children, live‐ or stillborn, weighed 500 g or more, and with a gestation period of at least 22 weeks. Methods. Chorionicity, abnormal umbilical artery Doppler waveforms, intrauterine weight (IUW) <10th centile and prenatal diagnosis of fetal anomaly were studied simultaneously as prognostic criteria. Chorionicity was confirmed at birth by placental pathology. Main outcome measures. Diagnosis of chorionicity/amnionicity and IUW <10th centile. Neonatal intensive care unit admission, occurrence of respiratory distress syndrome and perinatal mortality. Results. Prenatal misclassification of chorionicity/amnionicity after postnatal perinatal pathology review was 12%. The positive predictive value of IUW <10th centile diagnosis was 44% for the prediction of birthweight <10th centile. Prenatal diagnosis of mono‐ or dichorionic placentation was associated with increased neonatal morbidity in comparison with that of trichorionic triplets. Perinatal mortality was significantly increased where mono‐ or dichorionic placentation was diagnosed prenatally (OR: 4.2; CI: 1.04–17), IUW <10th centile (OR: 10; CI: 2.4–41), with raised odds for abnormal umbilical Doppler measurements (OR: 9.7; CI: 2–47) and fetal anomaly (OR: 6.4; CI: 1.4–28.9). Conclusion. Early prenatal diagnosis of chorionicity is of major importance in triplet pregnancy. Experienced sonographers must quickly evaluate any uncertain diagnosis. In cases of unknown chorionicity, other ultrasonographic criteria can highlight high‐risk triplet pregnancy, but at a later stage.
The influence of preoperative vaginal cleansing on postoperative infectious morbidity in abdominal total hysterectomy for benign indications
Authors: KJØLHEDE PREBEN , HALILI SHEFQET , LÖFGREN MATS
Published: February 2009

Objective. To evaluate whether vaginal cleansing reduces the risk of postoperative infection after abdominal total hysterectomy on benign indications and to analyze risk factors. Design. Retrospective cohort study. Setting. All clinics including patients in the Swedish National Register for Gynecological Surgery. Population. All 7,193 women who underwent abdominal total hysterectomy for benign indications from 2000 to 2007. Methods. Information on clinic routines for preoperative vaginal cleansing was obtained retrospectively in a postal survey. Associations between routines for vaginal cleansing and structured data from the Register were analyzed by means of multivariate logistic regression models. The main effect variable was postoperative infections defined as infections treated with antibiotics within six to eight weeks postoperatively, reported by the patient or the physician. Main outcome measures. Prevalence and risk factors for postoperative infections. Results. Prevalence of postoperative infections was 14.4%. The prevalence did not differ between those having had vaginal cleansing using chlorhexidine and those without vaginal cleansing, whereas using saline solution was encumbered with a significantly increased risk. Risk factors for postoperative infections were age >60, obesity, smoking, weight of the uterus, duration of hospital stay, blood transfusion, and peroperative injury of the urinary bladder or ureter. Conclusion. Vaginal cleansing using chlorhexidine solution did not reduce the risk of postoperative infections, whereas vaginal cleansing using saline solution seemed to increase the risk. Some risk factors for postoperative infectious morbidity seem to be preventable.
Comprehensive optimization process of paranasal sinus radiography
Authors: Saarakkala S. , Nironen K. , Hermunen H. , Aarnio J. , Heikkinen J.O.
Published: February 2009

Background: The optimization of radiological examinations is important in order to reduce unnecessary patient radiation exposure.

Purpose: To perform a comprehensive optimization process for paranasal sinus radiography at Mikkeli Central Hospital, Finland.

Material and Methods: Patients with suspicion of acute sinusitis were imaged with a Kodak computed radiography (CR) system ( n=20) and with a Philips digital radiography (DR) system ( n=30) using focus-detector distances (FDDs) of 110 cm, 150 cm, or 200 cm. Patients’ radiation exposure was determined in terms of entrance surface dose and dose-area product. Furthermore, an anatomical phantom was used for the estimation of point doses inside the head. Clinical image quality was evaluated by an experienced radiologist, and physical image quality was evaluated from the digital radiography phantom.

Results: Patient doses were significantly lower and image quality better with the DR system compared to the CR system. The differences in patient dose and physical image quality were small with varying FDD. Clinical image quality of the DR system was lowest with FDD of 200 cm. Further, imaging with FDD of 150 cm was technically easier for the technologist to perform than with FDD of 110 cm.

Conclusion: After optimization, it was recommended that the DR system with FDD of 150 cm should always be used at Mikkeli Central Hospital. We recommend this kind of comprehensive approach in all optimization processes of radiological examinations.
Analysis of Public Service Announcements on National Television, 2001–2006
Authors: Fuhrel-Forbis Andrea , Nadorff P. Gayle , Snyder Leslie B.
Published: February 2009

Although public service announcements (PSAs) are used extensively in social marketing campaigns, few studies have examined the overall landscape of PSAs. This article presents a comprehensive analysis of all PSAs aired on national television from 2001–2006. Data are from an all-inclusive industry database. Units of analysis were the number of ads, estimated amount of airtime, and estimated dollar value of airtime. Over 183,000 PSAs aired on average each year from 2001–2006, estimated to be worth about $1.6 billion per year. PSAs represented 2% of advertisements on national television, with more (30.5%) PSAs airing overnight between 1:00 am and 5:00 am than at other times of the day, and more appearing in the fall than other times of the year. The most common topic of PSAs was health. Sports programs contained a smaller percentage of PSAs than other types of programs. The results can help policymakers ensure that PSAs air in sufficient quantity and at effective times, inform campaign decisions about allocation of funds and placements of PSAs, and point to the need to monitor PSAs for each campaign.
Childhood Obesity Prevention in South Africa: Media, Social Influences, and Social Marketing Opportunities
Authors: Evans W. Douglas , Blitstein Jonathan , Lynch Christina , De Villiers Anniza , Draper Catherine , Steyn Nelia , Lambert Estelle V.
Published: February 2009

Obesity and childhood overweight is a worldwide epidemic that has significant long-term public health implications both in developed and developing countries. South Africa, which has a well-documented burden of HIV/AIDS, tuberculosis, and other infectious diseases, now also has an increasing burden of obesity and noncommunicable diseases (NCD) such as diabetes and cardiovascular diseases. This article describes results of formative research on childhood obesity risk factors with parents of school-age children in the Western Cape region of South Africa. We interviewed parents living in low-income urban, rural, and township communities on nutrition and physical activity, media use, and potential social marketing messages. Study aims were threefold: to collect formative information on media use and health knowledge, attitudes, beliefs, and behaviors to support the development of an obesity prevention social marketing campaign targeting youth; to identify parents' preferred sources of health information, and to obtain reactions to potential obesity prevention social marketing messages. Overall, the family and community nutrition and physical activity environments in the Western Cape are highly complex. Parents report major safety concerns, lack of organized markets or other sources of healthy foods in rural and township areas, and lack of resources for physical activity. We also identified preferred sources for health information primarily through print and radio, obtained information about possible channels to reach parents, and identified potential message strategies to promote healthy lifestyles similar to some HIV/AIDS social marketing campaigns in Africa. This information supports future childhood obesity prevention social marketing.
The effect of interstimulus interval on sequential effects in absolute identification
Authors: Matthews William J. , Stewart Neil
Published: February 2009

In absolute identification experiments, the participant is asked to identify stimuli drawn from a small set of items which differ on a single physical dimension (e.g., 10 tones which vary in frequency). Responses in these tasks show a striking pattern of sequential dependencies: The current response assimilates towards the immediately preceding stimulus but contrasts with the stimuli further back in the sequence. This pattern has been variously interpreted as resulting from confusion of items in memory, shifts in response criteria, or the action of selective attention, and these interpretations have been incorporated into competing formal models of absolute identification performance. In two experiments, we demonstrate that lengthening the time between trials increases contrast to both the previous stimulus and the stimulus two trials back. This surprising pattern of results is difficult to reconcile with the idea that sequential dependencies result from memory confusion or from criterion shifts, but is consistent with an account that emphasizes selective attention.
Perceptual learning in face processing: Comparison facilitates face recognition
Authors: Dwyer Dominic M. , Vladeanu Matei
Published: February 2009

Theoretical analyses of perceptual learning suggest that comparison between similar stimuli aids subsequent discrimination between them. The current studies examined whether the opportunity to compare a target face to other similar faces during a preexposure phase facilitated performance on a matching task. Performance was better when the target face had been presented in alternation with similar comparator faces than if that target had not been exposed before test. Exposure to the target face without comparators, or exposure alternating with dissimilar faces, improved performance relative to the nonexposed control but performance was not as good as when target exposure was given in alternation to similar comparison faces. The effects were not influenced by image changes between exposure and test. It is suggested that exposure to a face in comparison to similar stimuli focuses the central representation of a face on its unique features. In practical terms these results suggest that reliable identification of an individual from their photograph would be improved by viewing that photograph in comparison with photographs of similar people.
Short article: Sensory generalization and learning about novel colours by poultry chicks
Authors: Osorio Daniel , Ham Abigail D. , Gonda Zsusanna , Andrew Richard J.
Published: February 2009

In nature animals constantly encounter novel stimuli and need to generalize from known stimuli. The animal may then learn about the novel stimulus. Hull (1947) suggested that as they learn animals distinguish knowledge based on direct experience from inference by generalization and in support of this view suggested that if a subject is directly trained to a stimulus subsequent extinction of responses is slower than when the response is based on generalization. Such an effect is also predicted by Bayesian models that relate the rate of learning to uncertainty in the estimate of stimulus value. We find support for this prediction when chicks learn about a novel colour (orange) if the initial evaluation is based on similarity to known colours (red, yellow). Specifically, if an expected food reward is absent the rate of extinction of the response to the novel stimulus exceeds that for the familiar colours. Interestingly, the change in relative preference for novel and familiar stimuli occurs after a delay of an hour. This type of delay has not, to our knowledge, been reported in previous studies of single-trial learning, but given its importance of generalization in natural behaviour this type of learning may have wide relevance.
Short article: Visual similarity at encoding and retrieval in an item recognition task
Authors: Mate Judit , Baqués Josep
Published: February 2009

The aim of this experiment was to examine the effects of shape similarity in visual working memory using a six alternative recognition task of Chinese characters. Shape similarity among items was manipulated at both encoding and retrieval in order to assess in which phase similarity impairs recognition to a greater degree. Results revealed that performance is particularly facilitated by high discriminability at retrieval but also by the presence of similar items at encoding, as similarity simplifies the global representation of the display and reduces memory load. Moreover, results provide further evidence that the classical similarity effect can be reversed in the visual domain when item memory (as opposed to order) is assessed.
Cytosolic PLA2 is required for CTL-mediated immunopathology of celiac disease via NKG2D and IL-15
Authors: Tang Fangming , Chen Zhangguo , Ciszewski Cezary , Setty Mala , Solus Jason , Tretiakova Maria , Ebert Ellen , Han Jin , Lin Anning , Guandalini Stefano , Groh Veronika , Spies Thomas , Green Peter , Jabri Bana
Published: February 2009

IL-15 and NKG2D promote autoimmunity and celiac disease by arming cytotoxic T lymphocytes (CTLs) to cause tissue destruction. However, the downstream signaling events underlying these functional properties remain unclear. Here, we identify cytosolic phospholipase A2 (cPLA2) as a central molecule in NKG2D-mediated cytolysis in CTLs. Furthermore, we report that NKG2D induces, upon recognition of MIC+ target cells, the release of arachidonic acid (AA) by CTLs to promote tissue inflammation in association with target killing. Interestingly, IL-15, which licenses NKG2D-mediated lymphokine killer activity in CTLs, cooperates with NKG2D to induce cPLA2 activation and AA release. Finally, cPLA2 activation in intraepithelial CTLs of celiac patients provides an in vivo pathophysiological dimension to cPLA2 activation in CTLs. These results reveal an unrecognized link between NKG2D and tissue inflammation, which may underlie the emerging role of NKG2D in various immunopathological conditions and define new therapeutic targets.
Evolutionarily conserved recognition and innate immunity to fungal pathogens by the scavenger receptors SCARF1 and CD36
Authors: Means Terry K. , Mylonakis Eleftherios , Tampakakis Emmanouil , Colvin Richard A. , Seung Edward , Puckett Lindsay , Tai Melissa F. , Stewart Cameron R. , Pukkila-Worley Read , Hickman Suzanne E. , Moore Kathryn J. , Calderwood Stephen B. , Hacohen Nir , Luster Andrew D. , El Khoury Joseph
Published: February 2009

Receptors involved in innate immunity to fungal pathogens have not been fully elucidated. We show that the Caenorhabditis elegans receptors CED-1 and C03F11.3, and their mammalian orthologues, the scavenger receptors SCARF1 and CD36, mediate host defense against two prototypic fungal pathogens, Cryptococcus neoformans and Candida albicans. CED-1 and C03F11.1 mediated antimicrobial peptide production and were necessary for nematode survival after C. neoformans infection. SCARF1 and CD36 mediated cytokine production and were required for macrophage binding to C. neoformans, and control of the infection in mice. Binding of these pathogens to SCARF1 and CD36 was β-glucan dependent. Thus, CED-1/SCARF1 and C03F11.3/CD36 are β-glucan binding receptors and define an evolutionarily conserved pathway for the innate sensing of fungal pathogens.
Constitutive ablation of dendritic cells breaks self-tolerance of CD4 T cells and results in spontaneous fatal autoimmunity
Authors: Ohnmacht Caspar , Pullner Andrea , King Susan B.S. , Drexler Ingo , Meier Stefanie , Brocker Thomas , Voehringer David
Published: February 2009

Lack of immunological tolerance against self-antigens results in autoimmune disorders. During onset of autoimmunity, dendritic cells (DCs) are thought to be critical for priming of self-reactive T cells that have escaped tolerance induction. However, because DCs can also induce T cell tolerance, it remains unclear whether DCs are required under steady-state conditions to prevent autoimmunity. To address this question, we crossed CD11c-Cre mice with mice that express diphtheria toxin A (DTA) under the control of a loxP-flanked neomycin resistance (neoR) cassette from the ROSA26 locus. Cre-mediated removal of the neoR cassette leads to DTA expression and constitutive loss of conventional DCs, plasmacytoid DCs, and Langerhans cells. These DC-depleted (ΔDC) mice showed increased frequencies of CD4 single-positive thymocytes and infiltration of CD4 T cells into peripheral tissues. They developed spontaneous autoimmunity characterized by reduced body weight, splenomegaly, autoantibody formation, neutrophilia, high numbers of Th1 and Th17 cells, and inflammatory bowel disease. Pathology could be induced by reconstitution of wild-type (WT) mice with bone marrow (BM) from ΔDC mice, whereas mixed BM chimeras that received BM from ΔDC and WT mice remained healthy. This demonstrates that DCs play an essential role to protect against fatal autoimmunity under steady-state conditions.
Array-based genotyping inS.cerevisiaeusing semi-supervised clustering
Authors: Bourgon Richard , Mancera Eugenio , Brozzi Alessandro , Steinmetz Lars M. , Huber Wolfgang
Published: February 2009

Motivation: Microarrays provide an accurate and cost-effective method for genotyping large numbers of individuals at high resolution. The resulting data permit the identification of loci at which genetic variation is associated with quantitative traits, or fine mapping of meiotic recombination, which is a key determinant of genetic diversity among individuals. Several issues inherent to short oligonucleotide arrays—cross-hybridization, or variability in probe response to target—have the potential to produce genotyping errors. There is a need for improved statistical methods for array-based genotyping.

Results: We developed ssGenotyping (ssG), a multivariate, semi-supervised approach for using microarrays to genotype haploid individuals at thousands of polymorphic sites. Using a meiotic recombination dataset, we show that ssG is more accurate than existing supervised classification methods, and that it produces denser marker coverage. The ssG algorithm is able to fit probe-specific affinity differences and to detect and filter spurious signal, permitting high-confidence genotyping at nucleotide resolution. We also demonstrate that oligonucleotide probe response depends significantly on genomic background, even when the probe's specific target sequence is unchanged. As a result, supervised classifiers trained on reference strains may not generalize well to diverged strains; ssG's semi-supervised approach, on the other hand, adapts automatically.

Availability: The ssGenotyping software is implemented in R. It is currently available for download (www.ebi.ac.uk/∼bourgon/yeast_genotyping/ssG) and is being submitted to Bioconductor.

Contact:  bourgon@ebi.ac.uk

Supplementary information:  Supplementary data and a version including color figures are available at Bioinformatics online.
The ruggedness of protein–protein energy landscape and the cutoff for 1/r
n potentials
Authors: Ruvinsky Anatoly M. , Vakser Ilya A.
Published: February 2009

Motivation: Computational studies of the energetics of protein association are important for revealing the underlying fundamental principles and for designing better tools to model protein complexes. The interaction cutoff contribution to the ruggedness of protein–protein energy landscape is studied in terms of relative energy fluctuations for 1/rn potentials based on a simplistic model of a protein complex. This artificial ruggedness exists for short cutoffs and gradually disappears with the cutoff increase.

Results: The critical values of the cutoff were calculated for each of 11 popular power-type potentials with n=0÷9, 12 and for two thresholds of 5% and 10%. The artificial ruggedness decreases to tolerable thresholds for cutoffs larger than the critical ones. The results showed that for both thresholds the critical cutoff is a non-monotonic function of the potential power n. The functions reach the maximum at n=3÷4 and then decrease with the increase of the potential power. The difference between two cutoffs for 5% and 10% artificial ruggedness becomes negligible for potentials decreasing faster than 1/r12. The analytical results obtained for the simple model of protein complexes agree with the analysis of artificial ruggedness in a dataset of 62 protein–protein complexes, with different parameterizations of soft Lennard–Jones potential and two types of protein representations: all-atom and coarse-grained. The results suggest that cutoffs larger than the critical ones can be recommended for protein–protein potentials.

Contact:  vakser@ku.edu
Localization of individual mulloway (Argyrosomus japonicus) within a spawning aggregation and their behaviour throughout a diel spawning period
Authors: Parsons Miles J. , McCauley Robert D. , Mackie Michael C. , Siwabessy Paulus , Duncan Alec J.
Published: February 2009

Parsons, M. J., McCauley, R. D., Mackie, M. C., Siwabessy, P., and Duncan, A. J. 2009. Localization of individual mulloway (Argyrosomus japonicus) within a spawning aggregation and their behaviour throughout a diel spawning period. – ICES Journal of Marine Science, 66: 1007–1014. Mulloway (Argyrosomus japonicus) are a soniferous member of the Sciaenidae. During summer in the Swan River of Western Australia, individuals form spawning aggregations in turbid waters around high tide, during late afternoon and early evening. Mulloway produce pulsed vocalizations that are characteristic of the species and to an extent of individuals. Crepuscular passive acoustic recordings of vocalizing mulloway were collected from a four-hydrophone array during March 2008. Arrival-time differences proved the most robust technique for localization. Corroboration of fish position was observed in relative energy levels of calls, surface-reflected path differences, and relative range of successive calls by individuals. Discrete vocal characteristics of the tone-burst frequency and sound-pressure levels assisted the determination of caller identification. Calibration signals were located within a mean distance of 3.4 m. Three-dimensional locations, together with error estimates, were produced for 213 calls during a sample 4-min period in which 495 calls were audible. Examples are given of the movement and related errors for several fish successfully tracked from their vocalizations. Localization confirmed variations in calling rates by individuals, calling altitudes, and the propensity to vary call structure significantly over short periods, hitherto unreported in this species.
Coherent but overlapping expression of microRNAs and their targets during vertebrate development
Authors: Shkumatava Alena , Stark Alexander , Sive Hazel , Bartel David P.
Published: February 2009

MicroRNAs (miRNAs) are small noncoding RNAs that direct post-transcriptional repression of protein-coding genes. In vertebrates, each highly conserved miRNA typically regulates hundreds of target mRNAs. However, the precise relationship between expression of the miRNAs and that of their targets has remained unclear, in part because of the scarcity of quantitative expression data at cellular resolution. Here we report quantitative analyses of mRNA levels in miRNA-expressing cells of the zebrafish embryo, capturing entire miRNA expression domains, purified to cellular resolution using fluorescent-activated cell sorting (FACS). Focus was on regulation by miR-206 and miR-133 in the developing somites and miR-124 in the developing central nervous system. Comparison of wild-type embryos and those lacking miRNAs revealed predicted targets that responded to the miRNAs and distinguished miRNA-mediated mRNA destabilization from other regulatory effects. For all three miRNAs examined, expression of the miRNAs and that of their predicted targets usually overlapped. A few targets were expressed at higher levels in miRNA-expressing cells than in the rest of the embryo, demonstrating that miRNA-mediated repression can act in opposition to other regulatory processes. However, for most targets expression was lower in miRNA-expressing cells than in the rest of the embryo, indicating that miRNAs usually operate in concert with the other regulatory machinery of the cell.
Regulation of SR protein phosphorylation and alternative splicing by modulating kinetic interactions of SRPK1 with molecular chaperones
Authors: Zhong Xiang-Yang , Ding Jian-Hua , Adams Joseph A. , Ghosh Gourisankar , Fu Xiang-Dong
Published: February 2009

Phosphorylation is essential for the SR family of splicing factors/regulators to function in constitutive and regulated pre-mRNA splicing; yet both hypo- and hyperphosphorylation of SR proteins are known to inhibit splicing, indicating that SR protein phosphorylation must be tightly regulated in the cell. However, little is known how SR protein phosphorylation might be regulated during development or in response to specific signaling events. Here, we report that SRPK1, a ubiquitously expressed SR protein-specific kinase, directly binds to the cochaperones Hsp40/DNAjc8 and Aha1, which mediate dynamic interactions of the kinase with the major molecular chaperones Hsp70 and Hsp90 in mammalian cells. Inhibition of the Hsp90 ATPase activity induces dissociation of SRPK1 from the chaperone complexes, which can also be triggered by a stress signal (osmotic shock), resulting in translocation of the kinase from the cytoplasm to the nucleus, differential phosphorylation of SR proteins, and alteration of splice site selection. These findings connect the SRPK to the molecular chaperone system that has been implicated in numerous signal transduction pathways and provide mechanistic insights into complex regulation of SR protein phosphorylation and alternative splicing in response to developmental cues and cellular signaling.