bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-Cell Analysis of T-Cell Receptor Repertoire of HTLV-1 Tax-Specific Cytotoxic T Cells in Allogeneic Transplant Recipients with Adult T-Cell Leukemia/Lymphoma
Authors: Tanaka Yukie , Nakasone Hideki , Yamazaki Rie , Sato Ken , Sato Miki , Terasako Kiriko , Kimura Shun-ichi , Okuda Shinya , Kako Shinichi , Oshima Kumi , Tanihara Aki , Nishida Junji , Yoshikawa Toshiaki , Nakatsura Tetsuya , Sugiyama Haruo , Kanda Yoshinobu
Published: July 2010

Adult T-cell leukemia (ATL) is a lymphoproliferative malignancy associated with human T-cell lymphotropic virus type 1 (HTLV-1) infection. Recently, it has been shown that allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for ATL, and that HTLV-1 Tax-specific CD8+ cytotoxic T cells (CTL) contribute to the graft-versus-ATL effect. In the present study, we, for the first time, analyzed the T-cell receptor (TCR) repertoire of isolated Tax301–309 (SFHSLHLLF)-specific CTLs in HLA-A*2402+ ATL patients before and after allo-HSCT by single-cell reverse transcription-PCR. The Tax301–309-specific CTLs in bone marrow and peripheral blood showed highly restricted oligoclonal diversity. In addition, a unique conserved amino acid motif of “P-D/P-R” in TCR-β complementarity-determining region 3 in either BV7- or BV18-expressing CTLs was observed not only in all of the samples from ATL patients, but also in samples from the same patient before and after HSCT. Furthermore, the P-D/P-R motif–bearing CTL clones established from peripheral blood samples after HSCT exhibited strong killing activity against the HTLV-1–infected T cells of the patient. CTL clones were not established in vitro from samples prior to allo-HSCT. In addition, CTL clones with a strong killing activity were enriched in vivo after HSCT in the patient. Hence, Tax301–309-specific CTLs in ATL patients might have a preference for TCR construction and induce strong immune responses against the HTLV-1–infected T cells of patients, which contribute to the graft-versus-ATL effects after allo-HSCT. However, further analyses with a larger number of patients and more frequent sampling after allo-HSCT is required to confirm these findings. Cancer Res; 70(15); 6181–92. ©2010 AACR.
Interaction of TAp73 and Breast Cancer–Associated Gene 3 Enhances the Sensitivity of Cervical Cancer Cells in Response to Irradiation-Induced Apoptosis
Authors: Leung Thomas Ho-Yin , Ngan Hextan Yuen-Sheung
Published: July 2010

Identification of proteins that are involved in the sensitivity of radiotherapy of cancers is important to enhance the response to cancer treatment. Expression of TAp73 is associated with the sensitivity of radiotherapy in cervical cancer patients, suggesting it plays an important role in controlling radiosensitivity. Here, by using yeast two-hybrid system, we identify breast cancer–associated gene 3 (BCA3) as the first and novel protein interacting partner of TAp73. By coimmunoprecipitation and Western blot analysis, we confirm that TAp73 binds with and stabilizes BCA3 in cervical cancer cell line HeLa. Immunofluorescence staining indicates that BCA3 is localized in the cytoplasm and nucleus. Interestingly, when coexpressed with TAp73, BCA3 interacts and colocalizes with TAp73 at the mitochondria. Mutagenesis reveals that the oligomerization domain of TAp73 is responsible for the interaction with BCA3. Furthermore, BCA3 augments the transactivation activity of TAp73 on bax promoter and protein expression. In addition, the expression of BCA3 also increases the sensitivity of TAp73-transfected cells in response to γ-irradiation–induced apoptosis. Western blot analysis also shows that TAp73 and BCA3 induce activation of caspase-7 and caspase-9. In summary, these findings suggested that BCA3 is a novel protein partner of TAp73, and they cooperate with each other to exert tumor-suppressive functions and sensitize the response of cervical cancer cells to radiotherapy. Cancer Res; 70(16); 6486–96. ©2010 AACR.
Tumor-Specific CD8+ T Cells Expressing Interleukin-12 Eradicate Established Cancers in Lymphodepleted Hosts
Authors: Kerkar Sid P. , Muranski Pawel , Kaiser Andrew , Boni Andrea , Sanchez-Perez Luis , Yu Zhiya , Palmer Douglas C. , Reger Robert N. , Borman Zachary A. , Zhang Ling , Morgan Richard A. , Gattinoni Luca , Rosenberg Steven A. , Trinchieri Giorgio , Restifo Nicholas P.
Published: July 2010

T-cell–based immunotherapies can be effective in the treatment of large vascularized tumors, but they rely on adoptive transfer of substantial numbers (∼20 million) of tumor-specific T cells administered together with vaccination and high-dose interleukin (IL)-2. In this study, we report that ∼10,000 T cells gene-engineered to express a single-chain IL-12 molecule can be therapeutically effective against established tumors in the absence of exogenous IL-2 and vaccine. Although IL-12–engineered cells did not perist long-term in hosts, they exhibited enhanced functionality and were detected in higher numbers intratumorally along with increased numbers of endogenous natural killer and CD8+ T cells just before regression. Importantly, transferred T cells isolated from tumors stably overproduced supraphysiologic amounts of IL-12, and the therapeutic effect of IL-12 produced within the tumor microenvironment could not be mimicked with high doses of exogenously provided IL-12. Furthermore, antitumor effects could be recapitulated by engineering wild-type open-repertoire splenocytes to express both the single-chain IL-12 and a recombinant tumor-specific T-cell receptor (TCR), but only when individual cells expressed both the TCR and IL-12, indicating that arrested migration of T cells at the tumor site was required for their activities. Successful tumor eradication was dependent on a lymphodepleting preconditioning regimen that reduced the number of intratumoral CD4+ Foxp3+ T regulatory cells. Our findings reveal an approach to genetically modify T cells to reduce the cell number needed, eliminate the need for vaccines or systemic IL-2, and improve immunotherapy efficacy based on adoptive transfer of gene-engineered T cells. Cancer Res; 70(17); 6725–34. ©2010 AACR.
Overcoming Persistent Dependency on Androgen Signaling after Progression to Castration-Resistant Prostate Cancer
Authors: Yamaoka Masuo , Hara Takahito , Kusaka Masami
Published: July 2010

Prostate cancer is the most common form of cancer in males in the United States, and the second leading cause of cancer death. Initially, most cases of prostate cancer respond well to hormone therapy; however, resistance often develops rapidly, leading to castration-resistant prostate cancer (CRPC). Several mechanisms for castration resistance have been proposed, of which the most significant seems to be the “intracrine” production of androgens from adrenal androgen or intratumorally via the de novo route. This mechanism stimulates disease progression through reactivation of androgen receptor signaling in patients who have previously undergone castration therapy. 17,20-lyase is essential for androgen synthesis in both the adrenal glands and CRPC tissue, and some 17,20-lyase inhibitors and second-generation anti-androgens that were developed to treat CRPC are currently under clinical investigation, with encouraging preliminary data reported so far. However, resistance to some of these therapies has already been noted. The study of circulating tumor cells will likely be important not only to identify patients likely to receive benefit from this therapeutic approach, but also to further understand the molecular mechanisms of resistance. Clin Cancer Res; 16(17); 4319–24. ©2010 AACR.
A Single-Dose, Crossover, Placebo- and Moxifloxacin-Controlled Study to Assess the Effects of Neratinib (HKI-272) on Cardiac Repolarization in Healthy Adult Subjects
Authors: Hug Bruce , Abbas Richat , Leister Cathie , Burns Jaime , Sonnichsen Daryl
Published: July 2010

Purpose: Neratinib is an orally administered, small-molecule, irreversible pan-ErbB inhibitor in development for the treatment of ErbB2-positive breast cancer. This study assessed the effects of therapeutic and supratherapeutic neratinib concentrations on cardiac repolarization, in accordance with current regulatory guidance.

Experimental Design: This was a two-part study in healthy subjects. In part 1, subjects were randomized to receive placebo, 400 mg moxifloxacin, or 240 mg neratinib (therapeutic dose) following a high-fat meal. In part 2, after a washout period, subjects received placebo plus 400 mg ketoconazole or 240 mg neratinib plus ketoconazole (supratherapeutic dose). ANOVA was used to compare the baseline-adjusted QTc interval for neratinib with that of placebo (reference), and for neratinib plus ketoconazole with that of placebo plus ketoconazole (reference). Pharmacokinetic/pharmacodynamic analyses and categorical summaries of interval data were done. Assay sensitivity was evaluated by the effect of moxifloxacin on QTc compared with placebo.

Results: Sixty healthy subjects were enrolled in this study. The upper bounds of the 90% confidence interval for baseline-adjusted QTcN (population-specific corrected QT) were ≤10 milliseconds greater than the corresponding reference at all postdose time points under conditions of both therapeutic and supratherapeutic plasma concentrations of neratinib. Pharmacokinetic/pharmacodynamic analysis revealed no relationship between neratinib concentrations and QTc interval. No subjects had QTcI, QTcF, or QTcN intervals >450 milliseconds or change from baseline >30 milliseconds. Moxifloxacin produced a significant increase in QTcN compared with placebo (P < 0.05).

Conclusions: Therapeutic and supratherapeutic plasma concentrations of neratinib do not prolong the QTc interval in healthy subjects. Clin Cancer Res; 16(15); 4016–23. ©2010 AACR.
miR-192/miR-215 Influence 5-Fluorouracil Resistance through Cell Cycle-Mediated Mechanisms Complementary to Its Post-transcriptional Thymidilate Synthase Regulation
Authors: Boni Valentina , Bitarte Nerea , Cristobal Ion , Zarate Ruth , Rodriguez Javier , Maiello Evaristo , Garcia-Foncillas Jesus , Bandres Eva
Published: July 2010

Thymidylate synthase (TYMS) is a target of the most widely used chemotherapeutic agents against gastrointestinal malignancies, the fluoropyrimidine-based therapy. TYMS expression levels have been identified as predictive biomarkers for 5-fluoruracil (FU) response in colorectal cancer, but their clinical utility remains controversial. The complexity of fluoropyrimidine response must require more mechanisms that currently have not been completely elucidated. In this context, microRNAs (miRNA) may play a role in modulating chemosensitivity. By carrying out an in silico analysis coupled to experimental validation, we detected that miR-192 and miR-215 target TYMS expression in colorectal cancer cell lines. However, downregulation of TYMS by these miRNAs does not sensitize colorectal cancer cell lines to FU treatment. The overexpression of miR-192/215 significantly reduces cell proliferation by targeting cell cycle progression. This effect was partially associated with p53 status, because reduction of cell proliferation and cell cycle arrest was associated with p21 and p27 induction. The decrease of S-phase cells by these miRNAs mitigates the effects of S phase–specific drugs and suggests that other mechanisms different from TYMS overexpression are essential to direct FU resistance. Finally, ectopic expression of miR-192/215 might have stronger impact to predict FU response than TYMS inhibition. Prospective studies to elucidate the role of these miRNAs as predictive biomarkers to FU are necessary. Mol Cancer Ther; 9(8); 2265–75. ©2010 AACR.
p53-Dependent Induction of Prostate Cancer Cell Senescence by the PIM1 Protein Kinase
Authors: Zemskova Marina , Lilly Michael B. , Lin Ying-Wei , Song Jin H. , Kraft Andrew S.
Published: July 2010

The PIM family of serine threonine protein kinases plays an important role in regulating both the growth and transformation of malignant cells. However, in a cell line–dependent manner, overexpression of PIM1 can inhibit cell and tumor growth. In 22Rv1 human prostate cells, but not in Du145 or RWPE-2, PIM1 overexpression was associated with marked increases in cellular senescence, as shown by changes in the levels of β-galactosidase (SA-β-Gal), p21, interleukin (IL)-6 and IL-8 mRNA and protein. During early cell passages, PIM1 induced cellular polyploidy. As the passage number increased, markers of DNA damage, including the level of γH2AX and CHK2 phosphorylation, were seen. Coincident with these DNA damage markers, the level of p53 protein and genes transcriptionally activated by p53, such as p21, TP53INP1, and DDIT4, increased. In these 22Rv1 cells, the induction of p53 protein was associated not only with senescence but also with a significant level of apoptosis. The importance of the p53 pathway to PIM1-driven cellular senescence was further shown by the observation that expression of dominant-negative p53 or shRNA targeting p21 blocked the PIM1-induced changes in the DNA damage response and increases in SA-β-Gal activity. Likewise, in a subcutaneous tumor model, PIM1-induced senescence was rescued when the p53-p21 pathways are inactivated. Based on these results, PIM1 will have its most profound effects on tumorigenesis in situations where the senescence response is inactivated. Mol Cancer Res; 8(8); 1126–41. ©2010 AACR.
Protective Effect of Nicotine on Lipopolysaccharide-Induced Acute Lung Injury in Mice
Authors: Ni Yun Feng , Tian Feng , Lu Zi Fan , Yang Guo Dong , Fu Hai Yan , Wang Jian , Yan Xiao Long , Zhao Ya Chao , Wang Yun Jie , Jiang Tao
Published: July 2010

Background: Recently, nicotine administration has been shown to be a potent inhibitor of a variety of innate immune responses, including endotoxin-induced sepsis. Objective: It was the aim of this study to evaluate the effect of nicotine on attenuating lung injury and improving the survival in mice with lipopolysaccharide (LPS)-induced acute lung injury (ALI). Methods: ALI was induced in mice by intratracheal instillation of LPS (3 mg/ml). The mice received intratracheal instillation of nicotine (50, 250 and 500 µg/kg) before or after LPS administration. Pulmonary histological changes were evaluated by hematoxylin-eosin stain, and lung wet/dry weight ratios were observed. Concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and high mobility group box (HMGB)-1, as well as myeloperoxidase (MPO) activity were measured by enzyme-linked immunosorbent assay. The mortality rate was recorded and analyzed by the Kaplan-Meier method. Results: Nicotine pretreatment significantly attenuated the severity of lung injury and inhibited the production of TNF-α, IL-1β and HMGB-1 in mice with ALI. After LPS administration, the lung wet/dry weight ratios, as an index of lung edema, and MPO activity were also markedly reduced by nicotine pretreatment. Early treatment with a high dose of nicotine (500 µg/kg) after LPS administration decreased the mortality in mice with ALI, even when treatment was started 24 h after LPS administration. Conclusion: Nicotine attenuated the lung injury and reduced mortality in mice with LPS-induced ALI.
Molecular characterisation of Tyr530Ser and IVS16–1G>T mutations causing severe factor V deficiency
Authors: Zheng Weidong , Liu Yanhui , Luo Ying , Chen Zhihong , Wang Yan , Zhang Liyan , Gao Guoquan , Yao Zhibin
Published: July 2010

Our previous study reported a missense mutation (Tyr530Ser) and a splicing site mutation (IVS16–1G>T) in blood coagulation factor V (FV) gene in a two-year-old Chinese boy. However, the linkage between the mutations and severe FV deficiency and the underlying mechanism has not been elucidated. The present study was designed to investigate the effect of the two mutations and the possible pathogenetic mechanism. FV procoagulant activity showed tremendous decrease in the patient with two mutations. The bioinformatics analyses predicted that IVS16–1G>T mutation may cause the entire exon 17 of FV to be skipped in transcription and thereby result in a deletion mutant. To confirm the predicted results, the fragment of exon 16 to exon 18 containing IVS16–1G>T mutation was obtained by PCR and site-directed mutagenesis. IVS16–1G>T mutant and wild-type constructs were transfected into COS-7 cells. Sequence analysis showed that mutant transcript lacked the entire 180-bp length of exon 17. Moreover, compared to wild-type, the expression of the two mutant proteins was decreased and the procoagulant activity was also reduced when the deletion mutant cDNA and Tyr530Ser site mutant cDNA were transfected into COS-7 cells, respectively. Our results indicate that Tyr530Ser and IVS16–1G>T could be separately responsible for severe FV deficiency, while the phenotype in the proband could be caused by the combination effect of the two defects.
Zinc ions bind to and inhibit activated protein C
Authors: Zhu Tianqing , Ubhayasekera Wimal , Nickolaus Noëlle , Sun Wei , Tingsborg Susanne , Mowbray Sherry , Schedin-Weiss Sophia
Published: July 2010

Zn2+ ions were found to efficiently inhibit activated protein C (APC), suggesting a potential regulatory function for such inhibition. APC activity assays employing a chromogenic peptide substrate demonstrated that the inhibition was reversible and the apparent K
I was 13 ± 2 μM. k
cat was seven fold decreased whereas K
M was unaffected in the presence of 10 μM Zn2+. The inhibitory effect of Zn2+ on APC activity was also observed when factor Va was used as a substrate in an assay coupled to a prothrombinase assay. The interaction of Zn2+ with APC was accompanied by a reversible ~40% decrease in tryptophan fluorescence, consistent with the ion inducing a conformational change in the protein. The apparent K
D was 7.4 ± 1.5 μM and thus correlated well with the apparent K
I. In the presence of physiological Ca2+ concentration the K
I and K
D values were three to four fold enhanced, presum-ably due to the Ca2+-induced conformational change affecting the conformation of the Zn2+-binding site. The inhibition mechanism was non-competitive both in the absence and presence of Ca2+. Comparisons of sequences and structures suggested several possible sites for zinc binding. The magnitude of the apparent KI in relation to the blood and platelet concentrations of Zn2+ supports a physiological role for this ion in the regulation of anticoagulant activity of APC. These findings broaden the understanding of this versatile serine protease and enable the future development of potentially more efficient anticoagulant APC variants for treatments of thrombotic diseases.
Selective activation of the prostaglandin E2 receptor subtype EP2 or EP4 leads to inhibition of platelet aggregation
Authors: Yuhki Koh-ichi , Kojima Fumiaki , Yamada Takehiro , Fujino Takayuki , Hara Akiyoshi , Takayama Koji , Maruyama Takayuki , Yoshida Akitoshi , Narumiya Shuh , Kuriyama Shuhko , Kashiwagi Hitoshi , Ushikubi Fumitaka
Published: July 2010

The effect of selective activation of platelet prostaglandin (PG) E2 receptor subtype EP2 or EP4 on platelet aggregation remains to be determined. In platelets prepared from wild-type mice (WT platelets), high concentrations of PGE2 inhibited platelet aggregation induced by U-46619, a thromboxane receptor agonist. However, there was no significant change in the inhibitory effect of PGE2 on platelets lacking EP2 (EP2
–/– platelets) and EP4 (EP4
–/– platelets) compared with the inhibitory effect on WT platelets. On the other hand, AE1–259 and AE1–329, agonists for EP2 and EP4, respectively, potently inhibited U-46619 -induced aggregation with respective IC50 values of 590 ± 14 and 100 ± 4.9 nM in WT platelets, while the inhibition was significantly blunted in EP2
–/– and EP4
–/– platelets. In human platelets, AE1–259 and AE1–329 inhibited U-46619-induced aggregation with respective IC50 values of 640 ± 16 and 2.3 ± 0.3 nM. Notably, the inhibitory potency of AE1–329 in human platelets was much higher than that in murine platelets, while such a difference was not observed in the inhibitory potency of AE1–259. AE1–329 also inhibited adenosine diphosphate-induced platelet aggregation, and the inhibition was almost completely blocked by AE3–208, an EP4 antagonist. In addition, AE1–329 increased intracellular cAMP concentrations in a concentration- and EP4-dependent manner in human platelets. These results indicate that selective activation of EP2 or EP4 can inhibit platelet aggregation and that EP4 agonists are particularly promising as novel anti-platelet agents.
Incidence and predictors of venous thromboembolism in post-acute care patients
Authors: Ageno Walter , Airoldi Andrea , Bonizzoni Erminio , Campanini Mauro , Gussoni Gualberto , Silingardi Mauro , Valerio Antonella , Zilli Chiara , Iori Ido , Scannapieco Gianluigi ,   for the TERSICORE Study Group
Published: July 2010

Few studies have addressed the topic of venous thromboembolism (VTE) in patients hospitalised in rehabilitation facilities. This patient population is rapidly growing, and data aimed to better define VTE risk in this setting are needed. Primary aim of this prospective observational study was to evaluate the frequency of symptomatic, objectively confirmed VTE in a cohort of unselected consecutive patients admitted to rehabilitation facilities, after medical diseases or surgery. Further objectives were to assess overall mortality, to identify risk factors for VTE and mortality, and to assess the attitude of physicians towards thromboprophylaxis. A total of 3,039 patients were included in the study, and the median duration of hospitalisation was 26 days. Seventy-two patients (2.4%) had symptomatic VTE. The median time to VTE from admission to the long-term care unit was 13 days. According to multivariable analysis, previous VTE (hazard ratio 5.67, 95% confidence interval 3.30–9.77) and cancer (hazard ratio 2.26, 95% confidence interval 1.36–3.75) were significantly associated to the occurrence of VTE. Overall in-hospital mortality was 15.1%. Age over 75 years, male gender, disability, cancer, and the absence of thromboprophylaxis were significantly associated to an increased risk of death (multivariable analysis). In-hospital antithrombotic prophylaxis was administered to 75.1% of patients, and low-molecular-weight heparin was the most widely used agent. According to our study, patients admitted to rehabilitation facilities remain at substantially increased risk for VTE. Because this applies to the majority of these patients, there is a great need for clinical trials assessing optimal prophylactic strategies.
A New Tool for the Risk Stratification of Patients With Complex Coronary Artery Disease
Authors: Garg Scot , Sarno Giovanna , Garcia-Garcia Hector M. , Girasis Chrysafios , Wykrzykowska Joanna , Dawkins Keith D. , Serruys Patrick W. ,   on behalf of the ARTS-II Investigators
Published: July 2010

Background—

Presently, no effective risk model exists to predict long-term mortality or other major adverse cardiovascular and cerebrovascular events (MACCE) in those patients undergoing percutaneous coronary intervention (PCI). This study aimed to assess whether the Clinical SYNTAX Score (CSS) calculated by multiplying the SYNTAX Score to a modified ACEF score (age/ejection fraction +1 for each 10 mL the creatinine clearance <60 mL/min per 1.73 m
2
) would improve the ability of either score to predict mortality and MACCE.

Methods and Results—

The CSS was calculated in 512 patients enrolled in the ARTS-II study who had serum creatinine levels, ejection fraction, and body weight recorded at baseline. Clinical outcomes in terms of MACCE and mortality at 1- and 5-year follow-up were stratified according to CSS tertiles: CSS
LOW
≤15.6 (n=170), 15.6<CSS
MID
≤27.5 (n=171), and CSS
HIGH
>27.5 (n=171). At 1-year follow-up, rates of repeat revascularization and MACCE were significantly higher in the highest tertile group. At 5-year follow-up, CSS
HIGH
had a comparable rate of myocardial infarction, a trend toward a significantly higher rate of death, and significantly higher rates of repeat revascularization and overall MACCE compared with patients in the lower 2 tertiles. The respective C-statistics for the CSS, SYNTAX Score, and ACEF score for 5-year mortality were 0.69, 0.62, and 0.65 and for 5-year MACCE were 0.62, 0.59, and 0.57.

Conclusions—

An improvement in the ability of the SYNTAX Score to predict MACCE and mortality can be achieved by combining the SYNTAX Score with a simple clinical risk score incorporating age, ejection fraction, and creatinine clearance to produce the Clinical SYNTAX score.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00235170.
A First Attempt to Numerically Compute Forces on Birds in V Formation
Authors: Sewatkar C. M. , Sharma Atul , Agrawal Amit
Published: July 2010

A model for studying the flow forces experienced by cylinders placed in V formation is presented, and an elementary comparison with flocking birds is made. The cylinders are modeled as two-dimensional square bodies exposed to incoming flow at Reynolds number 100. The effects of angle of formation (α), streamwise spacing (Ss), and number of cylinders (N) on parameters such as the coefficient of drag, coefficient of lateral force, and Strouhal number are studied. It is observed that the drag experienced by the cylinders decreases with a decrease in the angle of formation. The leading cylinder experiences the smallest drag, irrespective of the angle. The drag becomes less than the drag on an isolated cylinder at certain angles depending on the position of the cylinder in the formation. The average drag on cylinders in V formation is found to be less than on an isolated cylinder, leading to energy saving when flying in formation. It is also noted that the cylinders experience a substantial lateral force. Study of this simple model may help better understand certain features of flocking birds.
Modeling Social Learning of Language and Skills
Authors: Vogt Paul , Haasdijk Evert
Published: July 2010

We present a model of social learning of both language and skills, while assuming—insofar as possible—strict autonomy, virtual embodiment, and situatedness. This model is built by integrating various previous models of language development and social learning, and it is this integration that, under the mentioned assumptions, provides novel challenges. The aim of the article is to investigate what sociocognitive mechanisms agents should have in order to be able to transmit language from one generation to the next so that it can be used as a medium to transmit internalized rules that represent skill knowledge. We have performed experiments where this knowledge solves the familiar poisonous-food problem. Simulations reveal under what conditions, regarding population structure, agents can successfully solve this problem. In addition to issues relating to perspective taking and mutual exclusivity, we show that agents need to coordinate interactions so that they can establish joint attention in order to form a scaffold for language learning, which in turn forms a scaffold for the learning of rule-based skills. Based on these findings, we conclude by hypothesizing that social learning at one level forms a scaffold for the social learning at another, higher level, thus contributing to the accumulation of cultural knowledge.
Somatic and Emotional Well-Being Among Turkish Immigrants in Belgium: Acculturation or Culture?
Authors: Beirens Koen , Fontaine Johnny R. J.
Published: July 2010

The present studies investigate differences in well-being between Turkish immigrants, Belgian majority members, and Turkish majority members. Furthermore, the relationships between two acculturation dimensions (adaptation and maintenance) and well-being is investigated within the immigrant group. In a first study, somatic well-being is studied in a sample of 519 Belgian majority members, 229 Turkish immigrants, and 232 Turkish majority members. Turkish immigrants reported the most somatic complaints, followed by Turkish majorities and Belgian majorities. No relationships with acculturation were found. In a second study, emotional well-being (sadness/anxiety, anger, and positive emotions) was investigated in 519 Belgians, 151 Turkish immigrants, and 200 Turkish majority members. No differences were found for sadness/anxiety. Turkish majority members report less anger than the other two groups. For positive emotions, Turkish majority members score the lowest, followed by the Turkish immigrant group and the Belgian majority members. In the immigrant group only adaptation was associated with more positive emotions. Both studies demonstrate that indices of well-being behave differently in cross-cultural comparative research.
Parenting Practices Among Fathers of a Cohort of Pacific Infants in New Zealand
Authors: Iusitini Leon , Wanzhen Gao  , Sundborn Gerhard , Paterson Janis
Published: July 2010

This study examined the nurturing and harsh disciplinary parenting practices of fathers of a cohort of Pacific children born in New Zealand. At the 12-month measurement point, 823 fathers completed a modified version of the Parent Behavior Checklist comprising 15 items, 10 forming a Nurturing subscale and 5 forming a Harsh Discipline subscale. Findings revealed that a majority of Pacific fathers never or rarely used harsh discipline with their 12-month-old child, and hitting with an object was extremely rare. Levels of nurturance were more mixed, with playing and praise being common, but provision and reading of books being relatively uncommon. Multivariate logistic regression showed that relatively low Nurturance scores were associated with cultural separation, lower formal education, and nonpartnered marital status. Relatively high Harsh Discipline scores were associated with partnered marital status, gambling, and harmful alcohol consumption. Relatively low Harsh Discipline scores were associated with Tongan ethnicity and cultural maintenance.
Health Behaviors and Use of Traditional Chinese Medicine Among the British Chinese
Authors: Rochelle Tina L. , Marks David F.
Published: July 2010

Health behaviors and use of traditional Chinese medicine among the British Chinese community were examined. One hundred and eighty-six British Chinese participants recruited from Chinese health and community centers across the United Kingdom completed the Cultural Health Belief and Value Survey. Results revealed that the majority of respondents used Western medicine. Respondents’ decisions to use Western medicine were influenced by cost of medicine and speed of recovery. Use of traditional Chinese medicine was significantly associated with a number of variables, including respondent speaking a Chinese dialect as his or her first language being, having a sense of cultural superiority, and believing that cultural values and religious beliefs influence health behavior. Concurrent use of traditional Chinese medicine and Western medicine was found to be common among respondents. Better understanding of the influence of traditional cultural and health beliefs could enable more culturally appropriate and effective health provision.
What Is the Meaning of “on Time”? The Sociocultural Nature of Punctuality
Authors: White Lawrence T. , Valk Raivo , Dialmy Abdessamad
Published: July 2010

University students ( N = 301) in Estonia, Morocco, and the United States read scenarios about various scheduled appointments and indicated the time at which a person arriving would be inappropriately early or inappropriately late. Participants also completed measures of time orientation, collectivism, and personality. Definitions of “on time” varied substantially across countries and across individuals but interacted in a regular fashion with specific features of appointments (e.g., the purpose of an appointment or the status of persons involved). Flexible definitions of “on time” were associated with youth, collectivist values, and a fatalistic orientation toward the present. Finally, definitions of “on time” were largely independent of personality traits. Taken as a whole, personal standards of punctuality appear to be best understood within a situational and sociocultural—rather than dispositional—framework.
Psychosocial Adjustment and Substance Use of Cambodian and Vietnamese Immigrant Youth
Authors: Lim May , Stormshak Elizabeth A. , Falkenstein Corrina A.
Published: July 2010

Southeast Asians living in the United States are a unique Asian immigrant population. They are considered one of the “newer” Asian immigrant groups, tend to be less affluent compared with their East and South Asian counterparts, and are steadily growing in number. Unfortunately, few studies have been conducted specifically about Southeast Asian immigrants. The lack of studies, coupled with the community’s growing mental health issues, suggests the need for increased research on this population. This study contributes to the literature by examining the extent to which identification with Vietnamese or Cambodian culture, peer relationships, and coping behaviors affect substance use among Cambodian and Vietnamese immigrant youth. A sample of 102 participants, age 12 to 18 years, completed self-report measures regarding these variables. Results indicate that identification with one’s culture of origin and coping behaviors moderate the relationship between deviant peer association and substance use. Results are discussed within a contextual model of problem behavior among Southeast Asian youth.
Unpacking Cultural Differences in Interpersonal Flexibility: Role of Culture-Related Personality and Situational Factors
Authors: Cheng Cecilia , Feixue Wang  , Golden Debra L.
Published: July 2010

This research aimed to unpack cultural differences in interpersonal flexibility by examining the impact of culture on interpersonal flexibility via self-construal. In Study 1, a cross-cultural comparison in levels of interpersonal flexibility was performed and the hypothesized mediating role of an interdependent self-construal was tested. Participants included 92 Chinese and 87 Caucasian American university students. Results showed that Chinese participants generally reported greater interpersonal flexibility than their Caucasian American counterparts. Interdependent self-construal accounted for country differences in interpersonal flexibility. Study 2 adopted a cultural-priming paradigm to determine the causal role of culture in context-dependent information processing and interpersonal flexibility. In the experiment, 120 Chinese participants were presented with Chinese cultural, American cultural, or control primes. The dependent measures were context dependency and flexible responses across different negotiation tasks. Compared with participants presented with American primes, those presented with Chinese primes reported more context-dependent thoughts and displayed greater discriminative responses across interpersonal situations.
Intergenerational Relationships in the Family: Ethnic, Socioeconomic, and Country Variations in Germany, Israel, Palestine, and Turkey
Authors: Kagitcibasi Cigdem , Ataca Bilge , Diri Aysesim
Published: July 2010

This study examines some aspects of intergenerational relationships in different sociocultural contexts. Using data from Germany, Israel, Palestine, and Turkey from the Value of Children and Intergenerational Relationships Project, mother—adolescent dynamics are studied. Mothers’ expectation of future support from grown-up offspring and the adolescents’ support to the mother are the main dependent variables under consideration. Socioeconomic standing, particularly mother’s education, cultural values concerning family independence or interdependence, intergenerational intimacy, and support are found to affect the dependent variables. Although on one hand systematic patterns of predicted interrelationships are found in line with Kagitcibasi’s theory of family change, the complexity of the dynamics involved and the diversity of the samples prevent drawing clear dimensions of variation based on the comparative analyses.
Adolescents’ Value of Children and Their Intentions to Have Children: A Cross-Cultural and Multilevel Analysis
Authors: Mayer Boris , Trommsdorff Gisela
Published: July 2010

This study contributes to research regarding the value of children (VOC) by comparing adolescents’ VOC and their intentions to have children across 12 cultures and by exploring the relations between these constructs at the individual and cultural levels using multilevel modeling. A total of 3,348 adolescents from 12 cultures participated in this study. On average, adolescents reported that they intended to have about two children and also reported emotional VOC as being highly important. Adolescents from cultures with a low as compared to a high level of economic development reported a higher importance of the utilitarian-normative VOC. Results of the multilevel analyses showed that the reported emotional VOC was positively related to the number of children adolescents intended to have at the individual level, whereas the utilitarian-normative VOC was not related to adolescents’ intention to have children. At the cultural level, the VOC dimensions were only partly related to adolescents’ intention to have children. The results are discussed with regard to adolescents’ future family orientation and in relation to the VOC approach.
Metabolic Syndrome, Periodontal Infection, and Dental Caries
Authors: Timonen P. , Niskanen M. , Suominen-Taipale L. , Jula A. , Knuuttila M. , Ylöstalo P.
Published: July 2010

Only a few studies have examined the association of metabolic syndrome with periodontal infection and dental caries. The aim in this study was to examine the association of metabolic syndrome with periodontal infection and dental caries using the European Group for the Study of Insulin Resistance (EGIR) definition and its separate components. This study population consisted of dentate, non-diabetic individuals aged 30 to 64 years (N = 2050) who had never smoked. Relative risks (RR) were estimated with Poisson regression models. Metabolic syndrome was associated with teeth with deepened periodontal pockets 4 mm deep or deeper [adjusted RR 1.19 (95% CI 1.01-1.42)], with pockets 6 mm deep or deeper [adjusted RR 1.50 (95% CI 0.96-2.36)], and carious teeth [adjusted RR 1.25 (95% CI 0.93-1.70)]. The results suggest that metabolic syndrome or some of its components are associated weakly with periodontal infection.
Westermarck, Freud, and the Incest Taboo: Does Familial Resemblance Activate Sexual Attraction?
Authors: Fraley R. Chris , Marks Michael J.
Published: July 2010

Evolutionary psychological theories assume that sexual aversions toward kin are triggered by a nonconscious mechanism that estimates the genetic relatedness between self and other. This article presents an alternative perspective that assumes that incest avoidance arises from consciously acknowledged taboos and that when awareness of the relationship between self and other is bypassed, people find individuals who resemble their kin more sexually appealing. Three experiments demonstrate that people find others more sexually attractive if they have just been subliminally exposed to an image of their opposite-sex parent (Experiment 1) or if the face being rated is a composite image based on the self (Experiment 2). This finding is reversed when people are aware of the implied genetic relationship (Experiment 3). These findings have implications for a century-old debate between E. Westermarck and S. Freud, as well as contemporary research on evolution, mate choice, and sexual imprinting.
Migraine with aura triggered by cardiac myxoma: Case report and literature review
Authors: de Ceuster Laura , van Diepen Ton , Koehler Peter J
Published: July 2010

We present a new case of cardiac myxoma triggering migraine auras. A 52-year-old woman was suffering from migraine attacks with aura. Magnetic resonance imaging (MRI) showed no abnormalities. Subsequently, she had a minor stroke with multiple ischaemic lesions bilaterally on repeat MRI. An echocardiogram showed a myxoma of the left atrial wall. After removal of the myxoma she was free of symptoms. In the past, seven cardiac myxoma associated migraine patients have been reported. Other cardiac abnormalities, patent foramen ovale in particular, are known to be associated with migraine with aura. We attempted to compare the mechanisms by which cardiac myxoma and other cardiac abnormalities could trigger cortical spreading depression leading to migraine with aura.
Diffuse alveolar hemorrhage in systemic lupus erythematosus: a retrospective study in China
Authors: Shen M. , Zeng X. , Tian X. , Zhang F. , Zeng X. , Zhang X. , Xu W.
Published: July 2010

The objective of this study was to determine the clinical features of systemic lupus erythematosus (SLE) patients with diffuse alveolar hemorrhage (DAH). The medical records of 29 patients with DAH among 2133 SLE patients admitted to Peking Union Medical College Hospital from January 2004 to January 2009 were reviewed in this retrospective study. It was found that hypoxemia (100%), dyspnea (90%), cough (79%) and fever (72%), rather than hemoptysis (66%), were the most common symptoms. The most common extrapulmonary presentation was renal involvement (90%). In about 60% of patients nosocomial infection was also present. The mean drop in hemoglobin was 32 ± 10.9 g/l. Mean Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) was 17 ± 9. All patients received high-dose corticosteroid therapy and most were also given immunosuppressive agents. Rates of concomitant nosocomial infection and mechanical ventilation in non-survivors were higher than those of survivors (p < 0.05). DAH is a rare and catastrophic event in SLE. DAH can occur at any stage of the disease course; it usually occurs in patients with active SLE, and is frequently complicated by lupus nephritis. Some patients may have no hemoptysis. Early aggressive management with high-dose steroids and cyclophosphamide is advocated. Lupus (2010) 19, 1326—1330.
Transplantation of umbilical cord mesenchymal stem cells alleviates lupus nephritis in MRL/lpr mice
Authors: Gu Z. , Akiyama K. , Ma X. , Zhang H. , Feng X. , Yao G. , Hou Y. , Lu L. , Gilkeson GS , Silver RM , Zeng X. , Shi S. , Sun L.
Published: July 2010

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease, which, despite the advances in immunosuppressive medical therapies, remains potentially fatal in some patients, especially in treatment-refractory patients. This study found that transplantation of umbilical cord mesenchymal stem cells (UC-MSCs) has the same therapeutic effect as transplantation of bone marrow mesenchymal stem cells (BM-MSCs), which has been reported to be efficient in treating SLE-related symptoms in MRL/lpr mice. Multi-treatment (at the 18th, 19th, and 20th weeks of age) of 1 × 106 UC-MSCs was able to decrease the levels of 24-h proteinuria, serum creatinine, and anti-double-stranded DNA (dsDNA) antibody, and the extent of renal injury such as crescent formation in MRL/lpr mice. A lower, but still significant, reduction in these parameters was also observed in mice receiving a single dose of UC-MSCs (at the 18th week). UC-MSCs treatment also inhibited expression of monocyte chemotactic protein-1 (MCP-1) and high-mobility group box 1 (HMGB-1) expression in a similar fashion. UC-MSCs labeled with carboxyfluorescein diacetate succinimidyl ester (CFSE) were found in the lungs and kidneys 1 week post infusion. In addition, after 11 weeks post UC-MSCs infusion, human cells were found in kidney of UC-MSCs-treated mice. These findings indicated that UC-MSCs transplantation might be a potentially promising approach in the treatment of lupus nephritis, possibly by inhibiting MCP-1 and HMGB-1 production. Lupus (2010) 19, 1502—1514.
Thrombotic microangiopathy and the antiphospholipid syndrome
Authors: Johnsen SJA , Valborgland T. , Gudlaugsson E. , Bostad L. , Omdal R.
Published: July 2010

The antiphospholipid syndrome (APS) comprises the association between vascular thrombosis, including microthrombosis, pregnancy morbidity and the coexistence of anti-phospholipid antibodies. Thrombotic microangiopathy (TMA) can be one of the manifestations of the APS and may involve any organ. This feature of the APS is probably less recognized by clinical doctors than venous thrombosis and recurrent abortions. This case report presents a patient who developed a widespread TMA with renal failure, gastric mucosa ulceration, urinary bladder ulcerations and a finger necrosis as part of the APS.
Community-Based Child Abuse Prevention: Outcomes Associated With a Differential Response Program in California
Authors: Conley Amy , Duerr Berrick Jill
Published: July 2010

Traditionally, the American child welfare system intervenes in cases of evident and severe maltreatment. Families in need of help, but who have not reached a crisis, are excluded from typical services. Some suggest that if these families were served, few would be rereferred to the child welfare system. California’s Differential Response (DR) has three tracks, of which ‘‘Track 1’’ targets families screened out of child protective services (CPS) and refers them to agencies that provide voluntary, home-based services and referrals. This study examined child-welfare trajectories for families receiving Track 1 DR services in one California county. Using survival analysis, treatment group children (N = 134) were compared to children eligible for services but denied due to program capacity (comparison group N = 511). Findings suggest no statistically significant differences between groups on the likelihood of a re-report following program participation, timing of maltreatment reports, or report investigations. The ability to draw strong conclusions from this study, however, is limited by selection bias because prior child maltreatment reports were more common in the treatment group. The intervention may provide families with important supports, but evidence for maltreatment prevention may not be supported. Future studies should examine potential effects on a range of family domains.
Review: Neurorehabilitation With Neural Transplantation
Authors: Döbrössy Máté , Busse Monica , Piroth Tobias , Rosser Anne , Dunnett Stephen , Nikkhah Guido
Published: July 2010

Cell replacement therapy has been tested clinically in Parkinson’s disease (PD) and Huntington’s disease (HD), epilepsy, spinal cord injury, and stroke. The clinical outcomes have been variable, perhaps partly because of the differing levels of preclinical, basic experimental evidence that was available prior to the trials. The most promising results have been seen in PD trials, with encouraging ones in HD. A common feature of most trials is that they have concentrated on the biological and technical aspects of transplantation without presupposing that the outcomes might be influenced by events after the surgery. The growing evidence of plasticity demonstrated by the brain and grafts in response to environmental and training stimuli such as rehabilitation interventions has been mostly neglected throughout the clinical application of cell therapy. This review suggests that a different approach may be required to maximize recovery: postoperative experiences, including rehabilitation with explicit behavioral retraining, could have marked direct as well as positive secondary effects on the integration and function of grafted cells in the host neural system. The knowledge gained about brain plasticity following brain damage needs to be linked with what we know about promoting intrinsic recovery processes and how this can boost neurobiological and surgical strategies for repair at the clinical level. With proof of principle now established, a rich area for innovative research with profound therapeutic application is open for investigation.