bluuebunny/crossref_metadata_2025 huggingface dataset:
Why follow? The interplay of leader categorization, identification, and feeling respected
Authors: Van Quaquebeke Niels , Eckloff Tilman
Published: January 2013

Guided by both social cognitive and identity-based perspectives of leadership, the present study investigated how and when the process of leader categorization results in greater leader effectiveness. Specifically, we propose that the relationship between leader categorization and subordinates’ openness toward leadership should be partially mediated by subordinates’ identification with their leaders. Furthermore, seeking to corroborate that the issue of self-esteem is the central ingredient in the identification process, we argue that the mediation should become weaker the more subordinates feel that they are being treated disrespectfully by their leaders, and thus are explicitly undermined in their efforts toward self-enhancement. The proposed mediating effect was tested and supported in two field studies ( N1 = 244, N2 = 645). In the second study, we also tested and found support for the proposed moderated mediation model. The theoretical and managerial consequences are discussed.
Leading groups: Leadership as a group process
Authors: Thomas Geoff , Martin Robin , Riggio Ronald E.
Published: January 2013

Although leadership is fundamentally a social psychological (and group) phenomenon, interest in the social psychology of leadership has waxed and waned over the years. The present article briefly reviews this chequered history and then discusses recent theoretical and empirical developments that extend the study of social cognition and social identity to the domain of leadership. In addition, we consider how the eight empirical articles that constitute this Special Issue relate to, and further, the study of leadership as a group process, and conclude by identifying fertile areas for future research.
Architects and Planners in the Middle of a Road War
Authors: Wong Sidney
Published: January 2013

In 1966, an interdisciplinary team led by architect and planners replanned a freeway system of Baltimore to meet “the social, economic, and esthetic needs.” But staying true to their mission, they had to side with the affected residents and clash with their client in the court of public opinions, through behind-the-scenes lobbying, and with sober debates about technical details. They fought the road war on behalf of fragmented freeway opposition groups and bought them valuable time to join together. Some architect–planners violated client–consultant obligations and conducted subversive actions such as leaking information, coaching the highway fighters, and ultimately, making them strong enough to form a powerful antiroad coalition.
Contextualizing Distributed Leadership Within Early Childhood Education
Authors: Heikka Johanna , Waniganayake Manjula , Hujala Eeva
Published: January 2013

This article seeks to establish a new research agenda on distributed leadership by linking early childhood and school leadership research. It begins with a discussion of how distributed leadership is conceptualized, including a discussion of the main features and meanings of distributed leadership as defined by key scholars who have maintained a sustained interest in this topic. It explores theoretical bases underpinning leadership research that have adopted a distributed leadership framework in general and within early childhood education organizations in particular. By critiquing the application of learning derived from school-based research within early childhood settings, this article aims to engage readers across different education sectors to collaborate in reconceptualizing distributed leadership in the future.
How Do They Manage? An Investigation of Early Childhood Leadership
Authors: Aubrey Carol , Godfrey Ray , Harris Alma
Published: January 2013

Early childhood (EC) leadership literature indicates few theoretically based studies identifying and testing different models and characteristics of leadership. Objectives were thus to identify, describe and analyse what leadership meant to key EC participants; to consider roles, responsibilities and characteristics; to investigate core components; to capture practice and judge how it was understood and enacted. A case-study approach used 12 sites and multiple data-gathering methods: questionnaires; interviews; and in-depth ‘day in the life’ video vignettes. Participants described their organizations as hierarchical in structure and traditional in strategic decision-making, yet collaborative in culture and operational functioning. Variation in leadership, management and administration patterns across settings indicated multiple leadership roles in diverse EC settings. Principal components analysis revealed that those with postgraduate qualifications favoured ‘leaders as guides’; those with professional heritages other than teaching leaned towards ‘leaders as strategists’; those with NVQ qualifications tended towards ‘leaders as motivators’; those with postgraduate qualifications also valued ‘leaders as business oriented’. New models of leadership are thus worthy of consideration. Leaders acknowledged difficulty in standing back and reflecting, recognizing an essential aspect of leadership was ongoing thinking and decision-making, inaccessible unless they ‘talked-aloud’ whilst engaging in professional practice. This suggests a need to increase self-understanding and alternative routes to problem-solving.
Neutrophil differentiation into a unique hybrid population exhibiting dual phenotype and functionality of neutrophils and dendritic cells
Authors: Matsushima Hironori , Geng Shuo , Lu Ran , Okamoto Takashi , Yao Yi , Mayuzumi Nobuyasu , Kotol Paul F. , Chojnacki Benjamin J. , Miyazaki Toru , Gallo Richard L. , Takashima Akira
Published: January 2013

Key Points

Both immature and mature neutrophils differentiate into a previously unrecognized hybrid population when cultured with GM-CSF. The resulting hybrids exhibit dual phenotype and functionality of both neutrophils and dendritic cells.
CD8α+ DCs can be induced in the absence of transcription factors Id2, Nfil3, and Batf3
Authors: Seillet Cyril , Jackson Jacob T. , Markey Kate A. , Brady Hugh J. M. , Hill Geoffrey R. , MacDonald Kelli P. A. , Nutt Stephen L. , Belz Gabrielle T.
Published: January 2013

Key Points

Transcription factors Batf3, Id2, and Nfil3 are not essential for induced CD8α+ DC generation. Induced CD8α+ DCs can cross-present cellular antigens.
Mechanisms of fibrin polymerization and clinical implications
Authors: Weisel John W. , Litvinov Rustem I.
Published: January 2013

Research on all stages of fibrin polymerization, using a variety of approaches including naturally occurring and recombinant variants of fibrinogen, x-ray crystallography, electron and light microscopy, and other biophysical approaches, has revealed aspects of the molecular mechanisms involved. The ordered sequence of fibrinopeptide release is essential for the knob-hole interactions that initiate oligomer formation and the subsequent formation of 2-stranded protofibrils. Calcium ions bound both strongly and weakly to fibrin(ogen) have been localized, and some aspects of their roles are beginning to be discovered. Much less is known about the mechanisms of the lateral aggregation of protofibrils and the subsequent branching to yield a 3-dimensional network, although the αC region and B:b knob-hole binding seem to enhance lateral aggregation. Much information now exists about variations in clot structure and properties because of genetic and acquired molecular variants, environmental factors, effects of various intravascular and extravascular cells, hydrodynamic flow, and some functional consequences. The mechanical and chemical stability of clots and thrombi are affected by both the structure of the fibrin network and cross-linking by plasma transglutaminase. There are important clinical consequences to all of these new findings that are relevant for the pathogenesis of diseases, prophylaxis, diagnosis, and treatment.
Bacterial translational regulations: high diversity between all mRNAs and major role in gene expression
Authors: Picard Flora , Milhem Hélène , Loubière Pascal , Laurent Béatrice , Cocaign-Bousquet Muriel , Girbal Laurence
Published: January 2013

Background

In bacteria, the weak correlations at the genome scale between mRNA and protein levels suggest that not all mRNAs are translated with the same efficiency. To experimentally explore mRNA translational level regulation at the systemic level, the detailed translational status (translatome) of all mRNAs was measured in the model bacterium Lactococcus lactis in exponential phase growth.

Results

Results demonstrated that only part of the entire population of each mRNA species was engaged in translation. For transcripts involved in translation, the polysome size reached a maximum of 18 ribosomes. The fraction of mRNA engaged in translation (ribosome occupancy) and ribosome density were not constant for all genes. This high degree of variability was analyzed by bioinformatics and statistical modeling in order to identify general rules of translational regulation. For most of the genes, the ribosome density was lower than the maximum value revealing major control of translation by initiation. Gene function was a major translational regulatory determinant. Both ribosome occupancy and ribosome density were particularly high for transcriptional regulators, demonstrating the positive role of translational regulation in the coordination of transcriptional networks. mRNA stability was a negative regulatory factor of ribosome occupancy and ribosome density, suggesting antagonistic regulation of translation and mRNA stability. Furthermore, ribosome occupancy was identified as a key component of intracellular protein levels underlining the importance of translational regulation.

Conclusions

We have determined, for the first time in a bacterium, the detailed translational status for all mRNAs present in the cell. We have demonstrated experimentally the high diversity of translational states allowing individual gene differentiation and the importance of translation-level regulation in the complex process linking gene expression to protein synthesis.
Homeostatic properties of Lactobacillus jensenii engineered as a live vaginal anti-HIV microbicide
Authors: Yamamoto Hidemi S , Xu Qiang , Fichorova Raina N
Published: January 2013

Background

Vaginal probiotics are investigated as a binary strategy for prevention of bacterial vaginosis and HIV. We applied an innovative experimental model using primary and immortalized human cervical and vaginal epithelial cells to assess the functional properties of Lactobacillus jensenii, a predominant constituent of the healthy vaginal microbiome, engineered to express the HIV-1 entry inhibitor modified cyanovirin-N (mCV-N). In this model bacteria colonize the epithelial cells over a period of 24-72 h. Staurosporine and the Toll-like receptor 2/6 ligand macrophage-activating lipopeptide-2 (MALP-2) serve as positive controls for apoptosis and proinflammatory activation, respectively. In 24-hour intervals, the colonized epithelium is assessed microscopically, supernatants are collected for measurement of soluble immunoinflammatory mediators and production of CV-N, and cells are lysed for assessment of: 1) apoptosis by cleaved versus total caspase-3 assay; 2) NF-κB activation by a luciferase reporter assay; or 3) epithelia-associated colony forming units (CFU) in Brucella agar.

Results

Wild type (WT) L. jensenii 1153 consistently colonized cervical and vaginal cells in the absence of epithelial damage and apoptosis. The bioengineered derivatives expressing mCV-N or control plasmids showed the same stable colonization pattern, which was reproducible between technologists and bacterial batches (CFU coefficient of variation <10% within and between experiments and epithelial cell types). MALP-2 activated NF-κB and caused fold-increased levels of proinflammatory mediators with clinically established significance in the cervicovaginal environment (IL-1α, IL-1β, IL-6, TNF-α, IL-8, RANTES, MIP-3α, and ICAM-1), measured by a multiplex electrochemiluminescence assay. At the same time levels of protective anti-inflammatory mediators interleukin 1 receptor antagonist (IL-1RA) and secretory leukocyte protease inhibitor (SLPI), both measured by ELISA, remained constant (IL-1RA) or moderately increased (SLPI). Similarly to MALP-2, colonization by L. jensenii WT activated NF-κB; however, unlike the synthetic TLR2/6 ligand, the live microorganisms did not induce significant changes in the secreted levels across all inflammation-associated proteins. The mCV-N production and function were confirmed by western blot and a HIV-1 gp120 binding assay, respectively. The bioengineered lactobacilli expressed mCV-N with anti-HIV activity preserved in the epithelial cell context and caused no significant immunoinflammatory changes as compared to the WT L. jensenii.

Conclusions

These results highlight the translational value of the colonization model and justify further clinical investigation of the homeostatic and anti-HIV effectiveness of the L. jensenii derivates.
IL-11 produced by breast cancer cells augments osteoclastogenesis by sustaining the pool of osteoclast progenitor cells
Authors: McCoy Erin M , Hong Huixian , Pruitt Hawley C , Feng Xu
Published: January 2013

Background

Interleukin (IL)-11, a cytokine produced by breast cancer, has been implicated in breast cancer-induced osteolysis (bone destruction) but the mechanism(s) of action remain controversial. Some studies show that IL-11 is able to promote osteoclast formation independent of the receptor activator of NF-κB ligand (RANKL), while others demonstrate IL-11 can induce osteoclast formation by inducing osteoblasts to secrete RANKL. This work aims to further investigate the role of IL-11 in metastasis-induced osteolysis by addressing a new hypothesis that IL-11 exerts effects on osteoclast progenitor cells.

Methods

To address the precise role of breast cancer-derived IL-11 in osteoclastogenesis, we determined the effect of breast cancer conditioned media on osteoclast progenitor cells with or without an IL-11 neutralizing antibody. We next investigated whether recombinant IL-11 exerts effects on osteoclast progenitor cells and survival of mature osteoclasts. Finally, we examined the ability of IL-11 to mediate osteoclast formation in tissue culture dishes and on bone slices in the absence of RANKL, with suboptimal levels of RANKL, or from RANKL-pretreated murine bone marrow macrophages (BMMs).

Results

We found that freshly isolated murine bone marrow cells cultured in the presence of breast cancer conditioned media for 6 days gave rise to a population of cells which were able to form osteoclasts upon treatment with RANKL and M-CSF. Moreover, a neutralizing anti-IL-11 antibody significantly inhibited the ability of breast cancer conditioned media to promote the development and/or survival of osteoclast progenitor cells. Similarly, recombinant IL-11 was able to sustain a population of osteoclast progenitor cells. However, IL-11 was unable to exert any effect on osteoclast survival, induce osteoclastogenesis independent of RANKL, or promote osteoclastogenesis in suboptimal RANKL conditions.

Conclusions

Our data indicate that a) IL-11 plays an important role in osteoclastogenesis by stimulating the development and/or survival of osteoclast progenitor cells and b) breast cancer may promote osteolysis in part by increasing the pool of osteoclast progenitor cells via tumor cell-derived IL-11. However, given the heterogeneous nature of the bone marrow cells, the precise mechanism by which IL-11 treatment gives rise to a population of osteoclast progenitor cells warrants further investigation.
Low intensity vs. self-guided Internet-delivered psychotherapy for major depression: a multicenter, controlled, randomized study
Authors: López-del-Hoyo Yolanda , Olivan Barbara , Luciano Juan V , Mayoral Fermín , Roca Miquel , Gili Margalida , Andres Eva , Serrano-Blanco Antoni , Collazo Francisco , Araya Ricardo , Baños Rosa , Botella Cristina , Magallón Rosa , García-Campayo Javier
Published: January 2013

Background

Major depression will become the second most important cause of disability in 2020. Computerized cognitive-behaviour therapy could be an efficacious and cost-effective option for its treatment. No studies on cost-effectiveness of low intensity vs self-guided psychotherapy has been carried out. The aim of this study is to assess the efficacy of low intensity vs self-guided psychotherapy for major depression in the Spanish health system.

Methods

The study is made up of 3 phases: 1.- Development of a computerized cognitive-behaviour therapy for depression tailored to Spanish health system. 2.- Multicenter controlled, randomized study: A sample (N=450 patients) with mild/moderate depression recruited in primary care. They should have internet availability at home, not receive any previous psychological treatment, and not suffer from any other severe somatic or psychological disorder. They will be allocated to one of 3 treatments: a) Low intensity Internet-delivered psychotherapy + improved treatment as usual (ITAU) by GP, b) Self-guided Internet-delivered psychotherapy + ITAU or c) ITAU. Patients will be diagnosed with MINI psychiatric interview. Main outcome variable will be Beck Depression Inventory. It will be also administered EuroQol 5D (quality of life) and Client Service Receipt Inventory (consume of health and social services). Patients will be assessed at baseline, 3 and 12 months. An intention to treat and a per protocol analysis will be performed.

Discussion

The comparisons between low intensity and self-guided are infrequent, and also a comparative economic evaluation between them and compared with usual treatment in primary. The strength of the study is that it is a multicenter, randomized, controlled trial of low intensity and self-guided Internet-delivered psychotherapy for depression in primary care, being the treatment completely integrated in primary care setting.

Trial registration

Clinical Trials NCT01611818
Genetic diversity of Plasmodium vivax clinical isolates from southern Pakistan using pvcsp and pvmsp1 genetic markers
Authors: Raza Afsheen , Ghanchi Najia K , Thaver Ali M , Jafri Sana , Beg Mohammad A
Published: January 2013

Background

Plasmodium vivax is the prevalent malarial species accounting for 70% of malaria burden in Pakistan; however, there is no baseline data on the circulating genotypes. Studies have shown that polymorphic loci of gene encoding antigens pvcsp and pvmsp1 can be used reliably for conducting molecular epidemiological studies. Therefore, this study aimed to bridge the existing knowledge gap on population structure on P. vivax from Pakistan using these two polymorphic genes.

Methods

During the period January 2008 to May 2009, a total of 250 blood samples were collected from patients tested slide positive for P. vivax, at the Aga Khan University Hospital, Karachi, or its collection units located in Baluchistan and Sindh Province. Nested PCR/RFLP was performed, using pvcsp and pvmsp1 markers to detect the extent of genetic diversity in clinical isolates of P. vivax from southern Pakistan.

Results

A total of 227/250 (91%) isolates were included in the analysis while the remainder were excluded due to negative PCR outcome for P.vivax. Pvcsp analysis showed that both VK 210 (85.5%, 194/227) and VK 247 type (14.5%, 33/227) were found to be circulating in P. vivax isolates from southern Pakistan. A total of sixteen and eighty-seven genotypes of pvcsp and pvmsp-1 were detected respectively.

Conclusion

This is the first report from southern Pakistan on characterization of P. vivax isolates confirming that extensively diverse pvcsp and pvmsp1 variants are present within this region. Results from this study provide valuable data on genetic diversity of P. vivax that will be helpful for further epidemiological studies.
Anemia in relation to body mass index and waist circumference among chinese women
Authors: Qin Yu , Melse-Boonstra Alida , Pan Xiaoqun , Yuan Baojun , Dai Yue , Zhao Jinkou , Zimmermann Michael B , Kok Frans J , Zhou Minghao , Shi Zumin
Published: January 2013

Background

This study aimed to investigate the relationship of anemia and body mass index among adult women in Jiangsu Province, China. Data were collected in a sub-national cross-sectional survey, and 1,537 women aged 20 years and above were included in the analyses. Subjects were classified by body mass index (BMI) categories as underweight, normal weight, overweight and obese according to the Chinese standard. Central obesity was defined as a waist circumference ≥ 80 cm. Anemia was defined as hemoglobin concentration < 12 g/dl. Prevalence ratios (PRs) of the relationship between anemia and BMI or waist circumference were calculated using Poisson regression.

Findings

Overall, 31.1% of the Chinese women were anemic. The prevalence of overweight, obesity and central obesity was 34.2%, 5.8% and 36.2%, respectively. The obese group had the highest concentrations of hemoglobin compared with other BMI groups. After adjustment for confounders, overweight and obese women had a lower PR for anemia (PR: 0.72, 95% CI: 0.62-0.89; PR: 0.59, 95% CI: 0.43-0.79). Central obesity was inversely associated with anemia.

Conclusion

In this Chinese population, women with overweight/obesity or central obesity were less likely to be anemic as compared to normal weight women. No measures are required currently to target anemia specifically for overweight and obese people in China.
Cross-cultural adaptation and validation of a Brazilian version of an instrument to assess impairments related to oral functioning of people with Down syndrome
Authors: Bonanato Karina , Pordeus Isabela A , Compart Thiago , Oliveira Ana Cristina , Allison Paul J , Paiva Saul M
Published: January 2013

Background

An instrument was developed in Canada to assess impairments related to oral functioning of individuals with four years of age or older with Down syndrome (DS). The present study attempted to carry out the cross-cultural adaptation and validation of the instrument for the Brazilian Portuguese language and to test its reliability and validity.

Findings

After translation and cross-cultural adaptation, the instrument was tested on caregivers of people with DS. Clinical examination for malocclusion was carried out in people with DS by two calibrated examiners. Inter and Intra examiner agreement was assessed by Intraclass Correlation Coefficient (ICC) and ranged from 0.92 to 0.97 respectively. Total of 157 people with DS and their caregivers were able to compose the sample. They were selected from eight institutions for people with DS in five cities of southeastern Brazil. The mean age of people with DS was 20.7 [±13.1] and for caregivers was 53.1 [±13.7]. The mean instrument score was 18.6 [±9.0]. Internal reliability ranged from 0.49 to 0.80 and external reliability ranged from 0.78 to 0.88. Construct validity was verified by significant correlations identified between malocclusion and the total instrument; and caregivers’ educational level and the instrument (p<0.05). Discriminant validity was proved as the instrument presented different mean comparing people with DS and non-DS (p<0.05).

Conclusions

Initial validity tests indicated that the instrument related to the oral health for people with DS may be a valid instrument to this segment of the population in Brazil.
RACK1 is involved in endothelial barrier regulation via its two novel interacting partners
Authors: Boratkó Anita , Gergely Pál , Csortos Csilla
Published: January 2013

Background

RACK1, receptor for activated protein kinase C, serves as an anchor in multiple signaling pathways. TIMAP, TGF-β inhibited membrane-associated protein, is most abundant in endothelial cells with a regulatory effect on the endothelial barrier function. The interaction of TIMAP with protein phosphatase 1 (PP1cδ) was characterized, yet little is known about its further partners.

Results

We identified two novel interacting partners of RACK1, namely, TGF-β inhibited membrane-associated protein, TIMAP, and farnesyl transferase. TIMAP is most abundant in endothelial cells where it is involved in the regulation of the barrier function. WD1-4 repeats of RACK1 were identified as critical regions of the interaction both with TIMAP and farnesyl transferase. Phosphorylation of TIMAP by activation of the cAMP/PKA pathway reduced the amount of TIMAP-RACK1 complex and enhanced translocation of TIMAP to the cell membrane in vascular endothelial cells. However, both membrane localization of TIMAP and transendothelial resistance were attenuated after RACK1 depletion. Farnesyl transferase, the enzyme responsible for prenylation and consequent membrane localization of TIMAP, is present in the RACK1-TIMAP complex in control cells, but it does not co-immunoprecipitate with TIMAP after RACK1 depletion.

Conclusions

Transient parallel linkage of TIMAP and farnesyl transferase to RACK1 could ensure prenylation and transport of TIMAP to the plasma membrane where it may attend in maintaining the endothelial barrier as a phosphatase regulator.
Predictive value of pre-procedural autoantibodies against M2-muscarinic acetylcholine receptor for recurrence of atrial fibrillation one year after radiofrequency catheter ablation
Authors: Zou Changhong , Zhang Zhiyong , Zhao Wenmin , Li Guang , Ma Guiling , Yang Xinchun , Zhang Jianjun , Zhang Lin
Published: January 2013

Background

Increasing evidences have suggested that autoantibodies against muscarinic-2 acetylcholine receptor (anti-M2-R) may play an important role in the development of atrial fibrillation (AF). Predictive value of pre-procedural anti-M2-R for the recurrence of AF after radiofrequency catheter ablation is still unclear.

Methods

Totally 76 AF patients with preserved left ventricular systolic function were prospectively enrolled and subjected to ablation after the detection of serum anti-M2-R by enzyme linked immunosorbent assay. These patients were given follow-up examination for one year after ablation. Risk estimation for the recurrence of AF was performed using the univariate and multivariate logistic regression.

Results

In AF group, serum anti-M2-R was significantly higher than that in the control group in terms of frequency (40.8% versus 11.7%; p < 0.001) and titer (1:116 versus 1:29; p < 0.001). Compared with paroxysmal AF patients, persistent AF patients had higher frequency (57.6% versus 27.9%; p = 0.009) and titer (1:132 versus 1:94; p = 0.012) for autoantibodies. During one-year follow-up examination after ablation, the recurrence of AF was observed in 25 (32.9%) patients. Multivariate analysis showed that pre-procedural serum anti-M2-R was an independent predictor for the recurrence of AF at the time point of 12 months after ablation (odds ratio: 4.701; 95% confidence interval: 1.590-13.894; p = 0.005).

Conclusions

In AF patients, the frequency and titer of serum anti-M2-R were significantly higher than those in the control group with sinus rhythm. Pre-procedural serum anti-M2-R was an independent predictor for the recurrence of AF one year after radiofrequency catheter ablation.
TLR-4 engagement of dendritic cells confers a BST-2/tetherin-mediated restriction of HIV-1 infection to CD4+T cells across the virological synapse
Authors: Blanchet Fabien P , Stalder Romaine , Czubala Magdalena , Lehmann Martin , Rio Laura , Mangeat Bastien , Piguet Vincent
Published: January 2013

Background

Dendritic cells and their subsets, located at mucosal surfaces, are among the first immune cells to encounter disseminating pathogens. The cellular restriction factor BST-2/tetherin (also known as CD317 or HM1.24) potently restricts HIV-1 release by retaining viral particles at the cell surface in many cell types, including primary cells such as macrophages. However, BST-2/tetherin does not efficiently restrict HIV-1 infection in immature dendritic cells.

Results

We now report that BST-2/tetherin expression in myeloid (myDC) and monocyte-derived dendritic cells (DC) can be significantly up-regulated by IFN-α treatment and TLR-4 engagement with LPS. In contrast to HeLa or 293T cells, infectious HIV-1 release in immature DC and IFN-α–matured DC was only modestly affected in the absence of Vpu compared to wild-type viruses. Strikingly, immunofluorescence analysis revealed that BST-2/tetherin was excluded from HIV containing tetraspanin-enriched microdomains (TEMs) in both immature DC and IFN-α–matured DC. In contrast, in LPS-mediated mature DC, BST-2/tetherin exerted a significant restriction in transfer of HIV-1 infection to CD4+T cells. Additionally, LPS, but not IFN-α stimulation of immature DC, leads to a dramatic redistribution of cellular restriction factors to the TEM as well as at the virological synapse between DC and CD4+T cells.

Conclusions

In conclusion, we demonstrate that TLR-4 engagement in immature DC significantly up-regulates the intrinsic antiviral activity of BST-2/tetherin, during cis-infection of CD4+T cells across the DC/T cell virological synapse. Manipulating the function and potency of cellular restriction factors such as BST-2/tetherin to HIV-1 infection, has implications in the design of antiviral therapeutic strategies.
Correlation of microrna-372 upregulation with poor prognosis in human glioma
Authors: Li Gang , Zhang Zhiguo , Tu Yanyang , Jin Tianbo , Liang Hongjuan , Cui Guangbin , He Shiming , Gao Guodong
Published: January 2013

MicroRNA-372 (miR-372) acts as either an oncogenic miRNA or an anti-oncomiR in various human malignancies. However, its roles in gliomas have not been elucidated. To address this problem, we here detected miR-372 expression in human gliomas and non-neoplastic brain tissues by real-time quantitative RT-PCR assay. The association of miR-372 expression with clinicopathological factors or prognosis of glioma patients was also statistically analyzed. As the results, miR-372 expression levels were significantly upregulated in glioma tissues compared to the corresponding non-neoplastic brain tissues (P<0.001). In addition, the high miR-372 expression was significantly associated with the advanced pathological grade (P=0.008) and the low Karnofsky performance score (KPS) of glioma patients (P=0.01). Moreover, the overall survival of patients with high miR-372 expression was dramatically shorter than those with low miR-372 expression (P<0.001). Furthermore, multivariate Cox regression analysis indicated that miR-372 expression was an independent prognostic factor for glioma patients (P=0.008). More importantly, subgroup analyses according to tumor pathological grade revealed that the cumulative overall survival of glioma patients with advanced pathological grades was significantly worse for high miR-372 expression group than for low miR-372 expression group (P<0.001), but no significant difference was found for patients with low pathological grades (P=0.08). Taken together, these data offer the convincing evidence for the first time that miR-372 may act as an oncogenic miRNA in gliomas and represent a potential regulator of aggressive development and a candidate prognostic marker for this malignancy, especially for advanced tumors with high pathological grades.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1707761328850011
Exposure of RML scrapie agent to a sodium percarbonate-based product and sodium dodecyl sulfate renders PrPScprotease sensitive but does not eliminate infectivity
Authors: Smith Jodi D , Nicholson Eric M , Foster Gregory H , Greenlee Justin J
Published: January 2013

Background

Prions, the causative agents of the transmissible spongiform encephalopathies, are notoriously difficult to inactivate. Current decontamination recommendations by the World Health Organization include prolonged exposure to 1 N sodium hydroxide or > 20,000 ppm sodium hypochlorite, or autoclaving. For decontamination of large stainless steel surfaces and equipment as in abattoirs, for example, these methods are harsh or unsuitable. The current study was designed to evaluate the effectiveness of a commercial product containing sodium percarbonate to inactivate prions. Samples of mouse brain infected with a mouse-adapted strain of the scrapie agent (RML) were exposed to a sodium percarbonate-based product (SPC-P). Treated samples were evaluated for abnormal prion protein (PrPSc)-immunoreactivity by western blot analysis, and residual infectivity by mouse bioassay.

Results

Exposure to a 21% solution of SPC-P or a solution containing either 2.1% or 21% SPC-P in combination with sodium dodecyl sulfate (SDS) resulted in increased proteinase K sensitivity of PrPSc. Limited reductions in infectivity were observed depending on treatment condition. A marginal effect on infectivity was observed with SPC-P alone, but an approximate 2–3 log10 reduction was observed with the addition of SDS, though exposure to SDS alone resulted in an approximate 2 log10 reduction.

Conclusions

This study demonstrates that exposure of a mouse-adapted scrapie strain to SPC-P does not eliminate infectivity, but does render PrPSc protease sensitive.
Phase II trial of first-line chemoradiotherapy with intensity-modulated radiation therapy followed by chemotherapy for synchronous unresectable distant metastases rectal adenocarcinoma
Authors: Zhu Ji , Lian Peng , Liu Fangqi , Xu Ye , Xu Junyan , Guan Zuqing , Liang Liping , Wang Minghe , Cai Sanjun , Zhang Zhen
Published: January 2013

Aims

Based on the hypothesis that first-line chemoradiation followed by chemotherapy was superior for primary tumor and non-inferior for distant lesions compared to chemotherapy alone in synchronous unresectable distant metastases rectal adenocarcinoma, this study was designed to assess the efficacy and safety of this strategy.

Materials and methods

Thirty two eligible patients received intensity modulated radiation therapy (45 Gy to the pelvis and a concomitant 10 Gy boost to the gross tumor), along with concurrent weekly capecitabine and oxaliplatin. Patients underwent radical surgery if all lesions were visually evaluated as resectable and received chemotherapy for a total of 6 months, whether pre- or post-operatively (definitive therapy group). The remaining patients received 6 months of consolidation chemotherapy followed by maintenance chemotherapy (non-definitive therapy group).

Results

The toxicities were acceptable, with radiation-induced dermatitis around the anal verge being the most common (18.8%). Fourteen patients underwent surgical resection of the rectal tumor, with 5 (35.7%) experiencing a pathological complete response. Nine out of 14 received definitive treatment, defined as R0 resections of all visible tumors. At a median follow-up of 12 months (range, 4–23 months), 2 cases were evaluated as local failure, and the median overall survival (OS) and progression free survival (PFS) for all 32 patients were 17.5 and 12 months, respectively. OS differed significantly in the definitive and non-definitive therapy groups (p=0.045), and PFS tended to differ (p=0.274).

Conclusion

It was demonstrated that the strategy of first-line chemoradiation followed by chemotherapy was effective and tolerable, especially for local control. OS and PFS were superior in patients who did than did not undergo curative therapy.
Radiation dose escalation for loco-regional recurrence of breast cancer after mastectomy
Authors: Skinner Heath D , Strom Eric A , Motwani Sabin B , Woodward Wendy A , Green Marjorie C , Babiera Gildy , Booser Daniel J , Meric-Bernstam Funda , Buchholz Thomas A
Published: January 2013

Background

Radiation is a standard component of treatment for patients with locoregional recurrence (LRR) of breast cancer following mastectomy. The current study reports the results of a 10% radiation dose escalation in these patients.

Methods

159 patients treated at MD Anderson Cancer Center between 1994-2006 with isolated LRR after mastectomy alone were reviewed. Patients in the standard treatment group (65 pts, 40.9%) were treated to 50 Gy comprehensively plus a boost of 10 Gy. The dose escalated group (94 pts, 59.1%) was treated to 54 Gy comprehensively and a minimum 12 Gy boost. Median dose in the standard dose and dose escalated group was 60 Gy (±1 Gy, 95% CI) and 66 Gy (±0.5 Gy, 95% CI) respectively. Median follow up for living patients was 94 months from time of recurrence.

Results

The actuarial five year locoregional control (LRC) rate was 77% for the entire study population. The five year overall survival and disease-free survival was 55% and 41%, respectively. On multivariate analysis, initial tumor size (p = 0.03), time to initial LRR (p = 0.03), absence of gross tumor at the time of radiation (p = 0.001) and Her2 status (p = 0.03) were associated with improved LRC. Five year LRC rates were similar in patients with a complete response to chemotherapy without surgery and patients with a complete surgical excision (77% vs 83%, p = NS), compared to a 63% LRC rate in patients with gross disease at the time of radiation (p = 0.024). LRC rates were 80% in the standard dose group and 75% in the dose escalated group (p = NS).

Conclusions

While LRR following mastectomy is potentially curable, distant metastasis and local control rates remain suboptimal. Radiation dose escalation did not appear to improve LRC. Given significant local failure rates, these patients are good candidates for additional strategies to improve their outcomes.
FCC – An automated rule-based processing tool for life science data
Authors: Barkow-Oesterreicher Simon , Türker Can , Panse Christian
Published: January 2013

Background

Data processing in the bioinformatics field often involves the handling of diverse software programs in one workflow. The field is lacking a set of standards for file formats so that files have to be processed in different ways in order to make them compatible to different analysis programs. The problem is that mass spectrometry vendors at most provide only closed-source Windows libraries to programmatically access their proprietary binary formats. This prohibits the creation of an efficient and unified tool that fits all processing needs of the users. Therefore, researchers are spending a significant amount of time using GUI-based conversion and processing programs. Besides the time needed for manual usage, such programs also can show long running times for processing, because most of them make use of only a single CPU. In particular, algorithms to enhance data quality, e.g. peak picking or deconvolution of spectra, add waiting time for the users.

Results

To automate these processing tasks and let them run continuously without user interaction, we developed the FGCZ Converter Control (FCC) at the Functional Genomics Center Zurich (FGCZ) core facility. The FCC is a rule-based system for automated file processing that reduces the operation of diverse programs to a single configuration task. Using filtering rules for raw data files, the parameters for all tasks can be custom-tailored to the needs of every single researcher and processing can run automatically and efficiently on any number of servers in parallel using all available CPU resources.

Conclusions

FCC has been used intensively at FGCZ for processing more than hundred thousand mass spectrometry raw files so far. Since we know that many other research facilities have similar problems, we would like to report on our tool and the accompanying ideas for an efficient set-up for potential reuse.
Bacterial feeding, Leishmania infection and distinct infection routes induce differential defensin expression in Lutzomyia longipalpis
Authors: Telleria Erich L , Sant’Anna Maurício R Viana , Alkurbi Mohammad O , Pitaluga André N , Dillon Rod J , Traub-Csekö Yara M
Published: January 2013

Background

Phlebotomine insects harbor bacterial, viral and parasitic pathogens that can cause diseases of public health importance. Lutzomyia longipalpis is the main vector of visceral leishmaniasis in the New World. Insects can mount a powerful innate immune response to pathogens. Defensin peptides take part in this response and are known to be active against Gram-positive and Gram-negative bacteria, and some parasites. We studied the expression of a defensin gene from Lutzomyia longipalpis to understand its role in sand fly immune response.

Methods

We identified, sequenced and evaluated the expression of a L. longipalpis defensin gene by semi-quantitative RT-PCR. The gene sequence was compared to other vectors defensins and expression was determined along developmental stages and after exposure of adult female L. longipalpis to bacteria and Leishmania.

Results

Phylogenetic analysis showed that the L. longipalpis defensin is closely related to a defensin from the Old World sand fly Phlebotomus duboscqi. Expression was high in late L4 larvae and pupae in comparison to early larval stages and newly emerged flies. Defensin expression was modulated by oral infection with bacteria. The Gram-positive Micrococcus luteus induced early high defensin expression, whilst the Gram-negative entomopathogenic Serratia marcescens induced a later response. Bacterial injection also induced defensin expression in adult insects. Female sand flies infected orally with Leishmania mexicana showed no significant difference in defensin expression compared to blood fed insects apart from a lower defensin expression 5 days post Leishmania infection. When Leishmania was introduced into the hemolymph by injection there was no induction of defensin expression until 72 h later.

Conclusions

Our results suggest that L. longipalpis modulates defensin expression upon bacterial and Leishmania infection, with patterns of expression that are distinct among bacterial species and routes of infection.
Cost-effectiveness of an Improving Access to Psychological Therapies service
Authors: Mukuria Clara , Brazier John , Barkham Michael , Connell Janice , Hardy Gillian , Hutten Rebecca , Saxon Dave , Dent-Brown Kim , Parry Glenys
Published: January 2013

Background

Effective psychological therapies have been recommended for common mental health problems, such as depression and anxiety, but provision has been poor. Improving Access to Psychological Therapies (IAPT) may provide a cost-effective solution to this problem.

Aims

To determine the cost-effectiveness of IAPT at the Doncaster demonstration site (2007–2009).

Method

An economic evaluation comparing costs and health outcomes for patients at the IAPT demonstration site with those for comparator sites, including a separate assessment of lost productivity. Sensitivity analyses were undertaken.

Results

The IAPT site had higher service costs and was associated with small additional gains in quality-adjusted life-years (QALYs) compared with its comparator sites, resulting in a cost per QALY gained of £29 500 using the Short Form (SF-6D). Sensitivity analysis using predicted EQ-5D scores lowered this to £16 857. Costs per reliable and clinically significant (RCS) improvement were £9440 per participant.

Conclusions

Improving Access to Psychological Therapies provided a service that was probably cost-effective within the usual National Institute for Health and Clinical Excellence (NICE) threshold range of £20 000-30 000, but there was considerable uncertainty surrounding the costs and outcome differences.
Increased Tricuspid Regurgitant Jet Velocity by Doppler Echocardiography in Adult Survivors of Childhood Cancer: A Report From the St Jude Lifetime Cohort Study
Authors: Armstrong Gregory T. , Joshi Vijaya M. , Zhu Liang , Srivastava Deokumar , Zhang Nan , Ness Kirsten K. , Stokes Dennis C. , Krasin Matthew T. , Fowler James A. , Robison Leslie L. , Hudson Melissa M. , Green Daniel M.
Published: January 2013

Purpose

To determine the prevalence of pulmonary hypertension, a late effect of cancer therapy not previously identified in aging survivors of childhood cancer, and associations with chest-directed radiation therapy (RT) and measures of current cardiac function, lung function, and exercise capacity.

Patients and Methods

Cross-sectional evaluation of 498 survivors at a median age of 38.0 years (range, 20.0 to 59.0 years) and a median of 27.3 years (range, 12.2 to 46.0 years) from primary cancer diagnosis was performed. Abnormal tricuspid regurgitant jet velocity (TRV) was defined as more than 2.8 m/s by Doppler echocardiography.

Results

Increased TRV was identified in 25.2% of survivors who received chest-directed RT and 30.8% of those who received more than 30 Gy. In multivariable models, increased TRV was associated with increasing dose of RT (1 to 19.9 Gy: odds ratio [OR], 2.09; 95% CI, 0.63 to 6.96; 20 to 29.9 Gy: OR, 3.46; 95% CI, 1.59 to 7.54; ≥ 30 Gy: OR, 4.54; 95% CI, 1.77 to 11.64 compared with no RT; P for trend < .001), body mass index more than 40 kg/m2 (OR, 3.89; 95% CI, 1.46 to 10.39), and aortic valve regurgitation (OR, 5.85; 95% CI, 2.05 to 16.74). Survivors with a TRV more than 2.8 m/s had increased odds (OR, 5.20; 95% CI, 2.5 to 11.0) of severe functional limitation on a 6-minute walk compared with survivors with a TRV ≤ 2.8 m/s.

Conclusion

A substantial number of adult survivors of childhood cancer who received chest-directed RT have an increased TRV and may have pulmonary hypertension as a result of both direct lung injury and cardiac dysfunction. Longitudinal follow-up and confirmation by cardiac catheterization are warranted.
Thyroid Hormones Decrease Plasma 1α,25-Dihydroxyvitamin D Levels Through Transcriptional Repression of the Renal 25-Hydroxyvitamin D3 1α-Hydroxylase Gene (CYP27B1)
Authors: Kozai Mina , Yamamoto Hironori , Ishiguro Mariko , Harada Nagakatsu , Masuda Masashi , Kagawa Tomohiro , Takei Yuichiro , Otani Ayako , Nakahashi Otoki , Ikeda Shoko , Taketani Yutaka , Takeyama Ken-ichi , Kato Shigeaki , Takeda Eiji
Published: January 2013

The primary determinant of circulating 1α,25-dihydroxyvitamin D (1,25[OH]2D) levels is the activity of 25-hydroxyvitamin D-1α-hydroxylase (cytochrome P450 27B1 [CYP27B1]) in the kidney. Hyperthyroid patients have been reported to have low levels of plasma 1,25(OH)2D. However, the detailed mechanism of thyroid hormone action on vitamin D metabolism is still poorly understood. The present study determined whether renal CYP27B1 gene expression was negatively regulated by thyroid hormones. T3-induced hyperthyroid mice showed marked decreases in plasma 1,25(OH)2D levels and in renal expression of CYP27B1 mRNA but no changes in plasma concentrations of calcium, PTH, or fibroblast growth factor-23. In addition, we observed that T3 administration significantly decreased plasma 1,25(OH)2D and renal CYP27B1 mRNA levels that were increased by low-calcium or low-phosphorus diets and induced hypocalcemia in mice fed a low-calcium diet. Promoter analysis revealed that T3 decreases the basal transcriptional activity of the CYP27B1 gene through thyroid hormone receptors (TRα and TRβ1) and the retinoid X receptor α (RXRα) in renal proximal tubular cells. Interestingly, we identified an everted repeat negative thyroid hormone response element (1α-nTRE) overlapping the sterol regulatory element (1α-SRE) and the TATA-box −50 to −20 base pairs from the human CYP27B1 gene transcription start site. Finally, we established that CYP27B1 gene transcription is positively regulated by SRE-binding proteins and that a T3-bound TRβ1/RXRα heterodimer inhibits SRE-binding protein-1c-induced transcriptional activity through the 1α-nTRE. These results suggest that transcriptional repression of the CYP27B1 gene by T3-bound TRs/RXRα, acting through the 1α-nTRE, results in decreased renal CYP27B1 expression and plasma 1,25(OH)2D levels.