bluuebunny/crossref_metadata_2025 huggingface dataset:
A Hierarchical Examination of the Immigrant Achievement Gap
Authors: Simms Kathryn
Published: January 2012

This study compared immigrant and nonimmigrant educational achievement (i.e., the immigrant gap) in math by reexamining the explanatory power of race and socioeconomic status (SES)—two variables, perhaps, most commonly considered in educational research. Four research questions were explored through growth curve modeling, factor analysis, and regression analysis on a sample of participants in the Early Childhood Longitudinal Study–Kindergarten Cohort of 1998 (ECLS-K) from kindergarten to eighth grade ( N = 6,861). Findings indicated that immigrant students who had been in the United States since at least their preschool years had lower math achievement than nonimmigrants when they began kindergarten; 1.75-generation students caught up to their nonimmigrant peers but second-generation students did not. Nationality played a greater role in determining immigrant performance than did race. Educational selectivity had significant explanatory power over SES in accounting for gaps between immigrant and nonimmigrant achievement. Mother’s educational selectivity was positively associated with parental involvement and center-based early childhood education. This study suggests that immigrant status alone is not a particularly powerful indicator of need for additional educational services nor is immigrant’s race in the absence of information about nationality. Because educational selectivity had positive and negative associations with educational achievement, encouraging parents with low educational selectivity to adopt the parenting processes of those with high educational selectivity cannot be recommended as a policy implication of this study. However, the incorporation of educational selectivity as a measure in future research is highly warranted due to its explanatory power regarding immigrant math achievement.
Intimacy and Belonging
Authors: Ganong Kathryn , Larson Erik
Published: January 2012

There is a paucity of systematic analysis of the relation between sexual activity and mental health. To address this gap, we ask whether sexual activity associates with lower levels of depression among older adults. We hypothesize that sexual activity—especially if it typically incorporates other forms of physical affection—may be a socially meaningful activity and may create intimacy that provides social uplift. We test this hypothesis against alternative hypotheses that relationship characteristics or physical health could account for any association between sex and depression. In addition, we consider whether there are gender dynamics that affect the association between sexual activity and depression. We analyze data from the National Social Life, Health, and Aging Project (NSHAP), a nationally representative survey of adults aged 57 to 85. Given findings of significant gendered aspects of depression, sexual activity, social support, and aging, we estimate separate models for women and men. Although we find differences between models for men and women for many control variables that correspond to gendered differences in depression, sexual activity that typically incorporates other forms of physical intimacy has a robust association with lower depression for both women and men.
An Exploration of the Effect of Community Engagement in Research on Perceived Outcomes of Partnered Mental Health Services Projects
Authors: Khodyakov Dmitry , Stockdale Susan , Jones Felica , Ohito Elizabeth , Jones Andrea , Lizaola Elizabeth , Mango Joseph
Published: January 2012

Mental health research projects address sensitive issues for vulnerable populations and are implemented in complex environments. Community-based participatory research approaches are recommended for health research on vulnerable populations, but little is known about how variation in participation affects outcomes of partnered research projects. We developed a conceptual model demonstrating the impact of community engagement in research on outcomes of partnered projects. We collected data on key constructs from community and academic leaders of 21 sampled partnered research projects in two cycles of a research center funded by the National Institute of Mental Health. We conducted empirical analyses to test the model. Our findings suggest that community engagement in research is positively associated with perceived professional development as well as political and community impact.
Engraftment of human HSCs in nonirradiated newborn NOD-scid IL2rγnull mice is enhanced by transgenic expression of membrane-bound human SCF
Authors: Brehm Michael A. , Racki Waldemar J. , Leif Jean , Burzenski Lisa , Hosur Vishnu , Wetmore Amber , Gott Bruce , Herlihy Mary , Ignotz Ronald , Dunn Raymond , Shultz Leonard D. , Greiner Dale L.
Published: January 2012

Immunodeficient mice engrafted with human HSCs support multidisciplinary translational experimentation, including the study of human hematopoiesis. Heightened levels of human HSC engraftment are observed in immunodeficient mice expressing mutations in the IL2-receptor common γ chain (IL2rg) gene, including NOD-scid IL2rγnull (NSG) mice. Engraftment of human HSC requires preconditioning of immunodeficient recipients, usually with irradiation. Such preconditioning increases the expression of stem cell factor (SCF), which is critical for HSC engraftment, proliferation, and survival. We hypothesized that transgenic expression of human membrane-bound stem cell factor Tg(hu-mSCF)] would increase levels of human HSC engraftment in nonirradiated NSG mice and eliminate complications associated with irradiation. Surprisingly, detectable levels of human CD45+ cell chimerism were observed after transplantation of cord blood–derived human HSCs into nonirradiated adult as well as newborn NSG mice. However, transgenic expression of human mSCF enabled heightened levels of human hematopoietic cell chimerism in the absence of irradiation. Moreover, nonirradiated NSG-Tg(hu-mSCF) mice engrafted as newborns with human HSCs rejected human skin grafts from a histoincompatible donor, indicating the development of a functional human immune system. These data provide a new immunodeficient mouse model that does not require irradiation preconditioning for human HSC engraftment and immune system development.
Overlapping and divergent signaling pathways of N-cadherin and VE-cadherin in endothelial cells
Authors: Giampietro Costanza , Taddei Andrea , Corada Monica , Sarra-Ferraris Gian Maria , Alcalay Myriam , Cavallaro Ugo , Orsenigo Fabrizio , Lampugnani Maria Grazia , Dejana Elisabetta
Published: January 2012

Endothelial cells (ECs) express 2 members of the cadherin family, VE and N-cadherin. Although VE-cadherin induces EC homotypic adhesion, N-cadherin function in ECs remains largely unknown. EC-specific inactivation of either VE or N-cadherin leads to early fetal lethality suggesting that these cadherins play a nonredundant role in vascular development. We report here that VE-cadherin negatively controls junctional localization and expression of N-cadherin by limiting p120-catenin availability and reducing β-catenin transcriptional activity. Using EC lines expressing either VE or N-cadherin we found that both cadherins inhibit cell proliferation and apoptosis. Both trigger the phosphatidylinositol-3-OH-kinase (PI3K)–AKT-Forkhead-box protein-O1 (FoxO1) pathway and reduce β-catenin transcriptional activity. The extent of signaling correlates with the total level of cadherins regardless of the type of cadherin expressed. In contrast, basal and fibroblast growth factor (FGF)–induced cell motility is promoted by N-cadherin and strongly inhibited by VE-cadherin. This opposite effect is partly because of the ability of VE-cadherin to associate with FGF receptor and the density-enhanced phosphatase-1 (Dep-1) which, in turn, inhibits receptor signaling. We conclude that VE and N-cadherin have both additive and divergent effects on ECs. Differences in signaling are due, in part, to cadherin association with growth factor receptors and modulation of their downstream signaling.
Histone/protein deacetylases and T-cell immune responses
Authors: Akimova Tatiana , Beier Ulf H. , Liu Yujie , Wang Liqing , Hancock Wayne W.
Published: January 2012

Clinical and experimental studies show that inhibition of histone/protein deacetylases (HDAC) can have important anti-neoplastic effects through cytotoxic and proapoptotic mechanisms. There are also increasing data from nononcologic settings that HDAC inhibitors (HDACi) can exhibit useful anti-inflammatory effects in vitro and in vivo, unrelated to cytotoxicity or apoptosis. These effects can be cell-, tissue-, or context-dependent and can involve modulation of specific inflammatory signaling pathways as well as epigenetic mechanisms. We review recent advances in the understanding of how HDACi alter immune and inflammatory processes, with a particular focus on the effects of HDACi on T-cell biology, including the activation and functions of conventional T cells and the unique T-cell subset, composed of Foxp3+ T-regulatory cells. Although studies are still needed to tease out details of the various biologic roles of individual HDAC isoforms and their corresponding selective inhibitors, the anti-inflammatory effects of HDACi are already promising and may lead to new therapeutic avenues in transplantation and autoimmune diseases.
Distinct TLR adjuvants differentially stimulate systemic and local innate immune responses in nonhuman primates
Authors: Kwissa Marcin , Nakaya Helder I. , Oluoch Herold , Pulendran Bali
Published: January 2012

TLR ligands (TLR-Ls) represent novel vaccine adjuvants, but their immunologic effects in humans remain poorly defined in vivo. In the present study, we analyzed the innate responses stimulated by different TLR-Ls in rhesus macaques. MPL (TLR4-L), R-848 (TLR7/8-L), or cytosine-phosphate-guanine oligodeoxynucleotide (TLR9-L) induced a rapid and robust expansion of blood neutrophils, with a concomitant reduction in PBMCs. Furthermore, all TLR-Ls induced rapid (3-8 hours) expansion of CD14+ monocytes, but only TLR7/8-L and TLR9-L mobilized the CD14+CD16+ and CD14dimCD16++ monocytes, and only TLR7/8-L and TLR9-L induced activation of myeloid dendritic cells (mDCs) and plasmacytoid DCs (pDCs), production of IP-10 and type-I IFN, and expression of type-I IFN–related and chemokine genes in the blood. In the draining lymph nodes (LNs), consistent with the effects in blood, all TLR-Ls induced expansion of CD14+ monocytes, but only TLR7/8-L and TLR9-L expanded the activated CD14+CD16+ cells. TLR4-L and TLR9-L differentially induced the expansion of mDCs and pDCs (1-3 days), but did not activate DCs. In contrast, TLR7/8-L did not induce DC expansion, but did activate mDCs. Finally, both TLR9-L and TLR7/8-L induced the expression of genes related to chemokines and type-I IFNs in LNs. Thus different TLR-Ls mediate distinct signatures of early innate responses both locally and systemically.
Differential switching to IgG and IgA in active smoking COPD patients and healthy controls
Authors: Brandsma Corry-Anke , Kerstjens Huib A.M. , van Geffen Wouter H. , Geerlings Marie , Postma Dirkje S. , Hylkema Machteld N. , Timens Wim
Published: January 2012

Several studies have demonstrated the presence of B-cell follicles and autoantibodies in chronic obstructive pulmonary disease (COPD). It is unclear against which antigens this B-cell response is directed and whether it contributes to development or worsening of disease.

We assessed different B-cell subsets in blood and lung tissue from COPD patients and controls, and compared differences in B-cell responsiveness to stimulation with lung-specific antigens.

Active smoking induced an adaptive immune response with relatively high levels of (class-switched) memory B-cells in blood and immunoglobulin (Ig)G memory B-cells in the lung. COPD smokers showed more switching to IgG, whereas healthy smokers switched more to IgA. COPD patients had higher levels of memory B-cells in the lung and stimulation with lung-specific antigens induced higher numbers of anti-decorin antibody-producing cells in COPD patients compared with healthy controls.

Differential switching to IgG and IgA indicates that the adaptive immune response to smoke differs between COPD patients and healthy controls. A higher level of memory B-cells in the lungs of COPD patients may reflect an antigen-specific immune response, which could be directed against decorin, as suggested by the induction of anti-decorin antibody-producing cells in response to antigen-specific stimulation in COPD patients.
Predicting survival in newly diagnosed idiopathic pulmonary fibrosis: a 3-year prospective study
Authors: Mura Marco , Porretta Maria A. , Bargagli Elena , Sergiacomi Gianluigi , Zompatori Maurizio , Sverzellati Nicola , Taglieri Amedeo , Mezzasalma Fabrizio , Rottoli Paola , Saltini Cesare , Rogliani Paola
Published: January 2012

The natural history of idiopathic pulmonary fibrosis (IPF) is not well defined and its clinical course is variable. We sought to investigate the survival and incidence of acute exacerbations (AEs) and their significant predictors in newly diagnosed patients.

70 patients newly diagnosed with IPF were prospectively followed for at least 3 yrs. Baseline evaluation included Medical Research Council dyspnoea score (MRCDS), 6-min walk test, pulmonary function tests, all of which were repeated at 6 months, and high-resolution computed tomography. A retrospective cohort of 68 patients was used for confirmation.

Mean survival from the time of diagnosis was 30 months, with a 3-yr mortality of 46%. A Risk stratificatiOn ScorE (ROSE) based on MRCDS >3, 6-min walking distance ≤72% predicted and composite physiologic index >41 predicted 3-yr mortality with high specificity. 6-month progression of ROSE predicted rapid progression. 3-yr incidence of AE was 18.6%, mostly occurring in the first 18 months; risk factors for AE were concomitant emphysema and low diffusing coefficient of the lung for carbon monoxide. Results were confirmed in an independent cohort of patients.

In newly diagnosed IPF, advanced disease at presentation, rapid progression and AEs are the determinants of 3-yr survival. The purpose of the multifactorial ROSE is to risk-stratify patients in order to predict survival and detect rapid disease progression.
Management of end-stage sarcoidosis: pulmonary hypertension and lung transplantation
Authors: Shlobin Oksana A. , Nathan Steven D.
Published: January 2012

Sarcoidosis is not only a multisystem, but also a multinational disease that is prevalent throughout the world, including Europe, the USA and Japan. Lung involvement in sarcoidosis is seemingly invariable, with up to 95% of patients manifesting some form of pulmonary disease during the course of their lifetime. The natural history of sarcoidosis in the lung is quite variable and spans the spectrum from spontaneous resolution to advanced fibrocystic disease in ∼5% of cases. Advanced sarcoidosis will be the subject of this review with a special focus on pulmonary hypertension and lung transplantation as a last-resort treatment option for some patients with end-stage disease.
Clinical validation of Xpert MTB/RIF for the diagnosis of extrapulmonary tuberculosis
Authors: Tortoli Enrico , Russo Cristina , Piersimoni Claudio , Mazzola Ester , Dal Monte Paola , Pascarella Michela , Borroni Emanuele , Mondo Alessandra , Piana Federica , Scarparo Claudio , Coltella Luana , Lombardi Giulia , Cirillo Daniela M.
Published: January 2012

Extrapulmonary tuberculosis (EPTB) accounts for more than 20% of tuberculosis (TB) cases. Xpert MTB/RIF (Xpert) (Cepheid, Sunnyvale, CA, USA) is a fully automated amplification system, for which excellent results in the diagnosis of pulmonary TB in highly endemic countries have been recently reported. We aimed to assess the performance of the Xpert system in diagnosing EPTB in a low incidence setting.

We investigated with Xpert a large number of consecutive extrapulmonary clinical specimens (1,476, corresponding to 1,068 patients) including both paediatric (494) and adult samples.

We found, in comparison with a reference standard consisting of combination of culture and clinical diagnosis of TB, an overall sensitivity and specificity of 81.3% and 99.8% for Xpert, while the sensitivity of microscopy was 48%. For biopsies, urines, pus and cerebrospinal fluids the sensitivity exceeded 85%, while it was slightly under 80% for gastric aspirates. It was, in contrast, lower than 50% for cavitary fluids. High sensitivity and specificity (86.9% and 99.7%, respectively) were also obtained for paediatric specimens.

Although the role of culture remains central in the microbiological diagnosis of EPTB, the sensitivity of Xpert in rapidly diagnosing the disease makes it a much better choice compared to smear microscopy. The ability to rule out the disease still remains suboptimal.
Noninvasive positive pressure ventilation in COPD
Authors: Windisch W.
Published: January 2012

Educational aims

To take up the ongoing debate on whether long-term noninvasive positive pressure ventilation (NPPV) should be applied in chronic obstructive pulmonary disease (COPD) patients with chronic hypercapnic respiratory failure.

To elucidate the impact of NPPV techniques on NPPV success in COPD.

To describe the technique and scientific evidence for the new concept of high-intensity NPPV.

To provide practical considerations on how to commence high-intensity NPPV.

To outline important unknowns regarding long-term NPPV in COPD patients.

Home mechanical ventilation, as provided by long-term NPPV, is a widely accepted treatment option for many patient groups with chronic hypercapnic respiratory failure, including also those with COPD, even though the rationale for long-term NPPV in COPD patients is still disputed. This is based on clinical observations that conventional NPPV using assisted ventilation and low mean inspiratory pressures of <18 cmH2O reportedly failed to effectively improve respiratory function, most importantly gas exchange, while outcomes are also not convincingly improved by the addition of long-term NPPV to long-term oxygen treatment.

Recently, however, a promising technique of NPPV has been described, which aims at maximally improving gas exchange by the use of controlled ventilation and considerably higher inspiratory pressures, typically ranging 20–40 cmH2O. This is known as high-intensity NPPV. This approach clearly contrasts with the conventional, low-intensity approach.

High-intensity NPPV has been shown to improve physiological parameters such as breathing pattern, gas exchange and lung function. In addition, it also provides clinical benefits, with improvements in dyspnoea, walking distance and specific aspects of health-related quality of life. The superiority of high- over low-intensity NPPV has been clearly established by randomised crossover trials.

Increasing evidence now exists to support the contention that long-term high-intensity NPPV offers a new therapeutic option in the treatment of hypercapnic COPD. However, the questions of whether high-intensity NPPV is also capable of improving survival and how to best select candidates to undergo long-term high-intensity NPPV remain pressing. This article also provides detailed practical descriptions of how to initiate high-intensity NPPV.
MIPHENO: data normalization for high throughput metabolite analysis
Authors: Bell Shannon M , Burgoon Lyle D , Last Robert L
Published: January 2012

Background

High throughput methodologies such as microarrays, mass spectrometry and plate-based small molecule screens are increasingly used to facilitate discoveries from gene function to drug candidate identification. These large-scale experiments are typically carried out over the course of months and years, often without the controls needed to compare directly across the dataset. Few methods are available to facilitate comparisons of high throughput metabolic data generated in batches where explicit in-group controls for normalization are lacking.

Results

Here we describe MIPHENO (Mutant Identification by Probabilistic High throughput-Enabled Normalization), an approach for post-hoc normalization of quantitative first-pass screening data in the absence of explicit in-group controls. This approach includes a quality control step and facilitates cross-experiment comparisons that decrease the false non-discovery rates, while maintaining the high accuracy needed to limit false positives in first-pass screening. Results from simulation show an improvement in both accuracy and false non-discovery rate over a range of population parameters (p < 2.2 × 10-16) and a modest but significant (p < 2.2 × 10-16) improvement in area under the receiver operator characteristic curve of 0.955 for MIPHENO vs 0.923 for a group-based statistic (z-score). Analysis of the high throughput phenotypic data from the Arabidopsis Chloroplast 2010 Project (http://www.plastid.msu.edu/) showed ~ 4-fold increase in the ability to detect previously described or expected phenotypes over the group based statistic.

Conclusions

Results demonstrate MIPHENO offers substantial benefit in improving the ability to detect putative mutant phenotypes from post-hoc analysis of large data sets. Additionally, it facilitates data interpretation and permits cross-dataset comparison where group-based controls are missing. MIPHENO is applicable to a wide range of high throughput screenings and the code is freely available as Additional file 1 as well as through an R package in CRAN.
Transcriptomic analysis of Chinese bayberry (Myrica rubra) fruit development and ripening using RNA-Seq
Authors: Feng Chao , Chen Ming , Xu Chang-jie , Bai Lin , Yin Xue-ren , Li Xian , Allan Andrew C , Ferguson Ian B , Chen Kun-song
Published: January 2012

Background

Chinese bayberry (Myrica rubra Sieb. and Zucc.) is an important subtropical fruit crop and an ideal species for fruit quality research due to the rapid and substantial changes that occur during development and ripening, including changes in fruit color and taste. However, research at the molecular level is limited by a lack of sequence data. The present study was designed to obtain transcript sequence data and examine gene expression in bayberry developing fruit based on RNA-Seq and bioinformatic analysis, to provide a foundation for understanding the molecular mechanisms controlling fruit quality changes during ripening.

Results

RNA-Seq generated 1.92 G raw data, which was then de novo assembled into 41,239 UniGenes with a mean length of 531 bp. Approximately 80% of the UniGenes (32,805) were annotated against public protein databases, and coding sequences (CDS) of 31,665 UniGenes were determined. Over 3,600 UniGenes were differentially expressed during fruit ripening, with 826 up-regulated and 1,407 down-regulated. GO comparisons between the UniGenes of these two types and interactive pathways (Ipath) analysis found that energy-related metabolism was enhanced, and catalytic activity was increased. All genes involved in anthocyanin biosynthesis were up-regulated during the fruit ripening processes, concurrent with color change. Important changes in carbohydrate and acid metabolism in the ripening fruit are likely associated with expression of sucrose phosphate synthase (SPS) and glutamate decarboxylase (GAD).

Conclusions

Mass sequence data of Chinese bayberry was obtained and the expression profiles were examined during fruit ripening. The UniGenes were annotated, providing a platform for functional genomic research with this species. Using pathway mapping and expression profiles, the molecular mechanisms for changes in fruit color and taste during ripening were examined. This provides a reference for the study of complicated metabolism in non-model perennial species.
Role of Mycobacterium tuberculosis pknD in the Pathogenesis of central nervous system tuberculosis
Authors: Be Nicholas A , Bishai William R , Jain Sanjay K
Published: January 2012

Background

Central nervous system disease is the most serious form of tuberculosis, and is associated with high mortality and severe neurological sequelae. Though recent clinical reports suggest an association of distinct Mycobacterium tuberculosis strains with central nervous system disease, the microbial virulence factors required have not been described previously.

Results

We screened 398 unique M. tuberculosis mutants in guinea pigs to identify genes required for central nervous system tuberculosis. We found M. tuberculosis pknD (Rv0931c) to be required for central nervous system disease. These findings were central nervous system tissue-specific and were not observed in lung tissues. We demonstrated that pknD is required for invasion of brain endothelia (primary components of the blood-brain barrier protecting the central nervous system), but not macrophages, lung epithelia, or other endothelia. M. tuberculosis pknD encodes a "eukaryotic-like" serine-threonine protein kinase, with a predicted intracellular kinase and an extracellular (sensor) domain. Using confocal microscopy and flow cytometry we demonstrated that the M. tuberculosis PknD sensor is sufficient to trigger invasion of brain endothelia, a process which was neutralized by specific antiserum.

Conclusions

Our findings demonstrate a novel in vivo role for M. tuberculosis pknD and represent an important mechanism for bacterial invasion and virulence in central nervous system tuberculosis, a devastating and understudied disease primarily affecting young children.
Screening of anti-dengue activity in methanolic extracts of medicinal plants
Authors: Tang Leon IC , Ling Anna PK , Koh Rhun Y , Chye Soi M , Voon Kenny GL
Published: January 2012

Background

Dengue fever regardless of its serotypes has been the most prevalent arthropod-borne viral diseases among the world population. The development of a dengue vaccine is complicated by the antibody-dependent enhancement effect. Thus, the development of a plant-based antiviral preparation promises a more potential alternative in combating dengue disease.

Methods

Present studies investigated the antiviral effects of standardised methanolic extracts ofAndrographis paniculata, Citrus limon, Cymbopogon citratus, Momordica charantia, Ocimum sanctumandPelargonium citrosumon dengue virus serotype 1 (DENV-1).

Results

O. sanctumcontained 88.6% of total flavonoids content, an amount that was the highest among all the six plants tested while the least was detected inM. charantia. In this study, the maximum non-toxic dose (MNTD) of the six medicinal plants was determined by testing the methanolic extracts against Vero E6 cellsin vitro. Studies also determined that the MNTD of methanolic extract was in the decreasing order ofM. charantia>C. limon>P. citrosum, O. sanctum>A. paniculata>C. citratus. Antiviral assay based on cytopathic effects (CPE) denoted by degree of inhibition upon treating DENV1-infected Vero E6 cells with MNTD of six medicinal plants showed thatA. paniculatahas the most antiviral inhibitory effects followed byM. charantia. These results were further verified with anin vitroinhibition assay using MTT, in which 113.0% and 98.0% of cell viability were recorded as opposed to 44.6% in DENV-1 infected cells. Although methanolic extracts ofO. sanctumandC. citratusshowed slight inhibition effect based on CPE, a significant inhibition was not reflected in MTT assay. Methanolic extracts ofC. limonandP. citrosumdid not prevent cytopathic effects or cell death from DENV-1.

Conclusions

The methanol extracts ofA. paniculataandM. charantiapossess the ability of inhibiting the activity of DENV-1 inin vitroassays. Both of these plants are worth to be further investigated and might be advantageous as an alternative for dengue treatment.
Novel immune-modulator identified by a rapid, functional screen of the parapoxvirus ovis (Orf virus) genome
Authors: McGuire Michael J , Johnston Stephen A , Sykes Kathryn F
Published: January 2012

Background

The success of new sequencing technologies and informatic methods for identifying genes has made establishing gene product function a critical rate limiting step in progressing the molecular sciences. We present a method to functionally mine genomes for useful activities in vivo, using an unusual property of a member of the poxvirus family to demonstrate this screening approach.

Results

The genome of Parapoxvirus ovis (Orf virus) was sequenced, annotated, and then used to PCR-amplify its open-reading-frames. Employing a cloning-independent protocol, a viral expression-library was rapidly built and arrayed into sub-library pools. These were directly delivered into mice as expressible cassettes and assayed for an immune-modulating activity associated with parapoxvirus infection. The product of the B2L gene, a homolog of vaccinia F13L, was identified as the factor eliciting immune cell accumulation at sites of skin inoculation. Administration of purified B2 protein also elicited immune cell accumulation activity, and additionally was found to serve as an adjuvant for antigen-specific responses. Co-delivery of the B2L gene with an influenza gene-vaccine significantly improved protection in mice. Furthermore, delivery of the B2L expression construct, without antigen, non-specifically reduced tumor growth in murine models of cancer.

Conclusion

A streamlined, functional approach to genome-wide screening of a biological activity in vivo is presented. Its application to screening in mice for an immune activity elicited by the pathogen genome of Parapoxvirus ovis yielded a novel immunomodulator. In this inverted discovery method, it was possible to identify the adjuvant responsible for a function of interest prior to a mechanistic study of the adjuvant. The non-specific immune activity of this modulator, B2, is similar to that associated with administration of inactivated particles to a host or to a live viral infection. Administration of B2 may provide the opportunity to significantly impact host immunity while being itself only weakly recognized. The functional genomics method used to pinpoint B2 within an ORFeome may be more broadly applicable to screening for other biological activities in an animal.
The influence of oral health conditions, socioeconomic status and home environment factors on schoolchildren's self-perception of quality of life
Authors: Paula Janice S , Leite Isabel CG , Almeida Anderso B , Ambrosano Glaucia MB , Pereira Antônio C , Mialhe Fábio L
Published: January 2012

Background

The objective this study was to investigate the influence of clinical conditions, socioeconomic status, home environment, subjective perceptions of parents and schoolchildren about general and oral health on schoolchildren's oral health-related quality of life (OHRQoL).

Methods

A sample of 515 schoolchildren, aged 12 years was randomly selected by conglomerate analysis from public and private schools in the city of Juiz de Fora, Brazil. The schoolchildren were clinically examined for presence of caries lesions (DMFT and dmft index), dental trauma, enamel defects, periodontal status (presence/absence of bleeding), dental treatment and orthodontic treatment needs (DAI). The SiC index was calculated. The participants were asked to complete the Brazilian version of Child Perceptions Questionnaire (CPQ11-14) and a questionnaire about home environment. Questions were asked about the presence of general diseases and children's self-perception of their general and oral health status. In addition, a questionnaire was sent to their parents inquiring about their socioeconomic status (family income, parents' education level, home ownership) and perceptions about the general and oral health of their school-aged children. The chi-square test was used for comparisons between proportions. Poisson's regression was used for multivariate analysis with adjustment for variances.

Results

Univariate analysis revealed that school type, monthly family income, mother's education, family structure, number of siblings, use of cigarettes, alcohol and drugs in the family, parents' perception of oral health of schoolchildren, schoolchildren's self perception their general and oral health, orthodontic treatment needs were significantly associated with poor OHRQoL (p < 0.001). After adjusting for potential confounders, variables were included in a Multivariate Poisson regression. It was found that the variables children's self perception of their oral health status, monthly family income, gender, orthodontic treatment need, mother's education, number of siblings, and household overcrowding showed a strong negative effect on oral health-related quality of life.

Conclusions

It was concluded that the clinical, socioeconomic and home environment factors evaluated exerted a negative impact on the oral health-related quality of life of schoolchildren, demonstrating the importance of health managers addressing all these factors when planning oral health promotion interventions for this population.
Performance assessment of IP over vehicular delay-tolerant networks through the VDTN@Lab testbed
Authors: Dias João AFF , Isento João NG , Silva Bruno MC , Soares Vasco NGJ , Rodrigues Joel JPC
Published: January 2012

Vehicular delay-tolerant network (VDTN) is a network architecture based on the delay-tolerant network paradigm, which was designed to provide low-cost asynchronous vehicular communications in environments with disruptions, intermittency, variable delays, and network partition. This article proposes a laboratory testbed for VDTNs, called VDTN@Lab. It aims to support research studies related with the design, emulation, performance evaluation, and diagnose of new VDTN protocols, services, and applications. It intends to demonstrate the applicability of VDTNs over multiple application environments. VDTN@Lab features an emulation capability, allowing live experiments with prototyped hardware and software embedded into robotic cards, desktop, and netbooks computers. The proposed prototype is demonstrated and evaluated with Epidemic, and Spray, and Wait routing protocols, using different combinations of scheduling and dropping policies, in scenarios with different vehicular mobility models (bus movement and random movement across roads).
Tumor necrosis factor-α-mediated threonine 435 phosphorylation of p65 nuclear factor-κB subunit in endothelial cells induces vasogenic edema and neutrophil infiltration in the rat piriform cortex following status epilepticus
Authors: Kim Ji-Eun , Ryu Hea Jin , Choi Soo Young , Kang Tae-Cheon
Published: January 2012

Background

Status epilepticus (SE) induces severe vasogenic edema in the piriform cortex (PC) accompanied by neuronal and astroglial damages. To elucidate the mechanism of SE-induced vasogenic edema, we investigated the roles of tumor necrosis factor (TNF)-α in blood-brain barrier (BBB) disruption during vasogenic edema and its related events in rat epilepsy models provoked by pilocarpine-induced SE.

Methods

SE was induced by pilocarpine in rats that were intracerebroventricularly infused with saline-, and soluble TNF p55 receptor (sTNFp55R) prior to SE induction. Thereafter, we performed Fluoro-Jade B staining and immunohistochemical studies for TNF-α and NF-κB subunits.

Results

Following SE, most activated microglia showed strong TNF-α immunoreactivity. In addition, TNF p75 receptor expression was detected in endothelial cells as well as astrocytes. In addition, only p65-Thr435 phosphorylation was increased in endothelial cells accompanied by SMI-71 expression (an endothelial barrier antigen). Neutralization of TNF-α by soluble TNF p55 receptor (sTNFp55R) infusion attenuated SE-induced vasogenic edema and neuronal damages via inhibition of p65-Thr435 phosphorylation in endothelial cells. Furthermore, sTNFp55R infusion reduced SE-induced neutrophil infiltration in the PC.

Conclusion

These findings suggest that impairments of endothelial cell functions via TNF-α-mediated p65-Thr 485 NF-κB phosphorylation may be involved in SE-induced vasogenic edema. Subsequently, vasogenic edema results in extensive neutrophil infiltration and neuronal-astroglial loss.
The soluble amino-terminal region of HVEM mediates efficient herpes simplex virus type 1 infection of gD receptor-negative cells
Authors: Baek Hyunjung , Kim Jae Hong , Noh Yoon Tae , Kwon Heechung
Published: January 2012

Background

Previous studies from our own and other labs reported the surprising finding that the soluble V domain of the herpes simplex virus type 1 (HSV-1) entry receptor nectin-1 can both block HSV infection of receptor-bearing cells and mediate infection of receptor-deficient cells. Here we show that this property is not unique to nectin-1. We generated a pair of truncated, soluble forms of the other major HSV-1 entry receptor, herpes virus entry mediator (HVEM or HveA), and examined its effects on HSV-1 infection of receptor-deficient cells.

Results

In cultures of CHO-K1 cells, sHveA102 comprising the two amino-terminal cysteine-rich pseudorepeats (CRPs) of HVEM enabled infection of greater than 80% of the cells at an MOI of 3, while sHveA162 comprising the complete ectodomain failed to mediate infection. Both sHveA102 and sHveA162 blocked infection of CHO-K1 cells stably expressing HVEM in a dose-dependent manner, indicating that both were capable of binding to viral gD. We found that sHveA102-mediated infection involves pH-independent endocytosis whereas HSV infection of HVEM-expressing CHO-K1 cells is known to be pH-dependent.

Conclusions

Our results suggest that the C-terminal portion of the soluble HVEM ectodomain inhibits gD activation and that this effect is neutralized in the full-length form of HVEM in normal infection.
Treatment and follow up of children with chronic hepatitis C in Albania
Authors: Velmishi Virtut , Dervishi Ermira , Cullufi Paskal , Bali Donjeta , Durro Vjollca
Published: January 2012

Background

Treatment of Hepatitis C in children has a better outcome than in adults, and for this reason the treatment had different views. However, in pediatric age hepatitis C is seen to have an evolution towards chronicity. Today is a normal option to treat chronic hepatitis C as early as possible according to certain criteria. The aim of this study is to show the results of treatment with interferon and ribavirin and the follow-up of children diagnosed with chronic hepatitis C in our service.

Patients and methods

This is a prospective study which has included children 3 up to 15 years old (13 boys and 4 girls) diagnosed with chronic hepatitis C. All patients underwent a certain protocol, including liver biopsy prior to treatment. Treatment consisted in use for 48 weeks of INF α-2b, 3 MIU/m2 three times a week s/c and ribavirin 15 mg/kg orally divided bid. Two patients were treated with PEGINF α-2b with dose 1.5 mcg/kg once a week s/c and ribavirin 15 mg/kg. After the treatment all patients have stayed under our control for an average period of 24 weeks.

Results

At the end of the treatment we detected a patient with HCV-RNA positive. End Treatment Viral Response was 94%. Six months later we found three patients who showed relapse of disease. Sustained Viral Response was approximately 83%

Conclusion

The combination therapy of interferon with Ribavirin in treatment of children with chronic hepatitis C provides a higher SVR when treatment is initiated at the earliest stages of hepatic changes. Side effects of therapy are insignificant in comparison with results obtained
Working towards a new psychiatry - neuroscience, technology and the DSM-5
Authors: Alam Sabina , Patel Jigisha , Giordano James
Published: January 2012

This Editorial introduces the thematic series on 'Toward a New Psychiatry: Philosophical and Ethical Issues in Classification, Diagnosis and Care' http://www.biomedcentral.com/series/newpsychiatry.
Lim homeobox genes in the Ctenophore Mnemiopsis leidyi: the evolution of neural cell type specification
Authors: Simmons David K , Pang Kevin , Martindale Mark Q
Published: January 2012

Background

Nervous systems are thought to be important to the evolutionary success and diversification of metazoans, yet little is known about the origin of simple nervous systems at the base of the animal tree. Recent data suggest that ctenophores, a group of macroscopic pelagic marine invertebrates, are the most ancient group of animals that possess a definitive nervous system consisting of a distributed nerve net and an apical statocyst. This study reports on details of the evolution of the neural cell type specifying transcription factor family of LIM homeobox containing genes (Lhx), which have highly conserved functions in neural specification in bilaterian animals.

Results

Using next generation sequencing, the first draft of the genome of the ctenophore Mnemiopsis leidyi has been generated. The Lhx genes in all animals are represented by seven subfamilies (Lhx1/5, Lhx3/4, Lmx, Islet, Lhx2/9, Lhx6/8, and LMO) of which four were found to be represented in the ctenophore lineage (Lhx1/5, Lhx3/4, Lmx, and Islet). Interestingly, the ctenophore Lhx gene complement is more similar to the sponge complement (sponges do not possess neurons) than to either the cnidarian-bilaterian or placozoan Lhx complements. Using whole mount in situ hybridization, the Lhx gene expression patterns were examined and found to be expressed around the blastopore and in cells that give rise to the apical organ and putative neural sensory cells.

Conclusion

This research gives us a first look at neural cell type specification in the ctenophore M. leidyi. Within M. leidyi, Lhx genes are expressed in overlapping domains within proposed neural cellular and sensory cell territories. These data suggest that Lhx genes likely played a conserved role in the patterning of sensory cells in the ancestor of sponges and ctenophores, and may provide a link to the expression of Lhx orthologs in sponge larval photoreceptive cells. Lhx genes were later co-opted into patterning more diversified complements of neural and non-neural cell types in later evolving animals.
Synergistic CD40 signaling on APCs and CD8 T cells drives efficient CD8 response and memory differentiation
Authors: Meunier Sylvain , Rapetti Laëtitia , Beziaud Laurent , Pontoux Christiane , Legrand Agnès , Tanchot Corinne
Published: January 2012

The role of CD4 help during CD8 response and memory differentiation has been clearly demonstrated in different experimental models. However, the exact mechanisms of CD4 help remain largely unknown and preclude replacement therapy to develop. Interestingly, studies have shown that administration of an agonist aCD40ab can substitute CD4 help in vitro and in vivo, whereas the targets of this antibody remain elusive. In this study, we address the exact role of CD40 expression on APCs and CD8 T cells using aCD40ab treatment in mice. We demonstrate that aCD40 antibodies have synergetic effects on APCs and CD8 T cells. Full efficiency of aCD40 treatment requires CD40 expression on both populations: if one of these cell populations is CD40-deficient, the CD8 T cell response is impaired. Most importantly, direct CD40 signaling on APCs and CD8 T cells affects CD8 T cell differentiation differently. In our model, CD40 expression on APCs plays an important but dispensable role on CD8 T cell expansion and effector functions during the early phase of the immune response. Conversely, CD40 on CD8 T cells is crucial and nonredundant for their progressive differentiation into memory cells. Altogether, these results highlight that CD40–CD40L-dependent and independent effects of CD4 help to drive a complete CD8 T cell differentiation.
PPAR-γ Activation Restores Pancreatic Islet SERCA2 Levels and Prevents β-Cell Dysfunction under Conditions of Hyperglycemic and Cytokine Stress
Authors: Kono Tatsuyoshi , Ahn Geonyoung , Moss Dan R. , Gann Liann , Zarain-Herzberg Angel , Nishiki Yurika , Fueger Patrick T. , Ogihara Takeshi , Evans-Molina Carmella
Published: January 2012

The maintenance of intracellular Ca2+ homeostasis in the pancreatic β-cell is closely regulated by activity of the sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) pump. Our data demonstrate a loss of β-cell SERCA2b expression in several models of type 2 diabetes including islets from db/db mice and cadaveric diabetic human islets. Treatment of 832/13 rat INS-1-derived cells with 25 mm glucose and the proinflammatory cytokine IL-1β led to a similar loss of SERCA2b expression, which was prevented by treatment with the peroxisome proliferator-activated receptor (PPAR)-γ agonist, pioglitazone. Pioglitazone was able to also protect against hyperglycemia and cytokine-induced elevations in cytosolic Ca2+ levels, insulin-secretory defects, and cell death. To determine whether PPAR-γ was a direct transcriptional regulator of the SERCA2 gene, luciferase assays were performed and showed that a −259 bp region is sufficient to confer PPAR-γ transactivation; EMSA and chromatin immunoprecipitation experiments confirmed that PPAR-γ directly binds a PPAR response element in this proximal region. We next sought to characterize the mechanisms by which SERCA2b was down-regulated. INS-1 cells were exposed to high glucose and IL-1β in time course experiments. Within 2 h of exposure, activation of cyclin-dependent kinase 5 (CDK5) was observed and correlated with increased serine-273 phosphorylation of PPAR-γ and loss of SERCA2 protein expression, findings that were prevented by pioglitazone and roscovitine, a pharmacological inhibitor of CDK5. We conclude that pioglitazone modulates SERCA2b expression through direct transcriptional regulation of the gene and indirectly through prevention of CDK5-induced phosphorylation of PPAR-γ.
Theorizing Neoliberal Urban Development
Authors: Tochterman Brian
Published: January 2012

This article considers the role of theory in neoliberal urban development/redevelopment practice in the past half-century. Specifically it reconsiders the writings of Jane Jacobs, one of the most important figures in defining the so-called urban crisis of the 1960s and 1970s. With a vision at once liberal and conservative, Jacobs established a political and economic fluidity that allowed successors to manipulate her innovative theories as they saw fit. The works of one such disciple, Richard Florida, are examined here at length. Florida has interpreted the recent turn toward neoliberal cultural, tourism-focused, and consumer-driven urban development and merged it with Jacobs's theories in order to cast himself as a key public advocate for “creative-class” planning with only marginal success and even less accountability. Despite popular and scholarly critiques of the creative-class model, Florida's celebrity and the popularity of his theories among public officials and economic elites alike have entrenched neoliberal urban planning as the dominant paradigm, not unlike Jacobs's transformative work in the 1960s. Placing Jacobs and Florida within the global phalanx of neoliberal visionaries contributes to the larger historiographical project of understanding neoliberalism's origins in the political economy of our own time.