bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural Killer Cells Are Involved in Acute Lung Immune Injury Caused by Respiratory Syncytial Virus Infection
Authors: Li Fengqi , Zhu Hanqing , Sun Rui , Wei Haiming , Tian Zhigang 
Published: December 2011

ABSTRACT
It is known that respiratory syncytial virus (RSV) is the main cause of bronchiolitis and pneumonia in young children. RSV infection often leads to severe acute lung immunopathology, but the underlying immune mechanisms are not yet fully elucidated. Here, we found that RSV infection induced severe acute lung immune injury and promoted the accumulation and activation of lung natural killer (NK) cells at the early stage of infection in BALB/c mice. Activated lung NK cells highly expressed activating receptors NKG2D and CD27 and became functional NK cells by producing a large amount of gamma interferon (IFN-γ), which was responsible for acute lung immune injury. NK cell depletion significantly attenuated lung immune injury and reduced infiltration of total inflammatory cells and production of IFN-γ in bronchoalveolar lavage fluid (BALF). These data show that NK cells are involved in exacerbating the lung immune injury at the early stage of RSV infection via IFN-γ secretion.
CRM1-Dependent Transport Supports Cytoplasmic Accumulation of Adenoviral Early Transcripts
Authors: Schmid Melanie , Gonzalez Ramon A. , Dobner Thomas 
Published: December 2011

ABSTRACT
The life cycle of adenoviruses is divided by convention into early and late phases, separated by the onset of viral genome replication. Early events include virus adsorption, transport of the genome into the nucleus, and the expression of early genes. After the onset of viral DNA replication, transcription of the major late transcription unit (MLTU) and thereby synthesis of late proteins is induced. These steps are controlled by an orchestra of regulatory processes and require import of the genome and numerous viral proteins into the nucleus, as well as active transport of viral transcripts and proteins from the nucleus to the cytoplasm. The latter is achieved by exploiting the shuttling functions of cellular transport receptors, which normally stimulate the nuclear export of cellular mRNA and protein cargos. A set of adenoviral early and late proteins contains a leucine-rich nuclear export signal of the HIV-1 Rev type, known to be recognized by the cellular export receptor CRM1. However, a role for CRM1-dependent export in supporting adenoviral replication has not been established. To address this issue in detail, we investigated the impact of two different CRM1 inhibitors on several steps of the adenoviral life cycle. Inhibition of CRM1 led to a reduction in viral early and late gene expression, viral genome replication, and progeny virus production. For the first time, our findings indicate that CRM1-dependent shuttling is required for the efficient export of adenoviral early mRNA.
Role of O-Glycosylation and Expression of CD43 and CD45 on the Surfaces of Effector T Cells in Human T Cell Leukemia Virus Type 1 Cell-to-Cell Infection
Authors: Mazurov Dmitriy , Ilinskaya Anna , Heidecker Gisela , Filatov Alexander 
Published: December 2011

ABSTRACTWe used replication-dependent retroviral vectors to identify cell surface antigens involved in the cell-to-cell transmission of human T cell leukemia virus type 1 (HTLV-1). We generated monoclonal antibodies (MAbs) against Jurkat T cells and selected several IgM MAbs that strongly inhibited HTLV-1 but not human immune deficiency virus type 1 (HIV-1) cell-to-cell infection. These MAbs recognized the so-called Tn antigen (GalNAcα1-O-Ser/Thr) that arises on Jurkat cells from a mutation in the T-synthase-specific chaperone Cosmc and the consequent loss ofO-glycan elongation. Anti-Tn MAbs precipitated two majorO-glycan carrier proteins, CD43 and CD45, and caused a strong aggregation of Jurkat cells. The restoration of O-glycosylation in Jurkat cells by stably transducing the wild-typeCosmcgene resulted in a 3- to 4-fold increase in the level of surface expression of CD43 and enhanced HTLV-1 transmission 10-fold in comparison to that of parental cells. The short hairpin RNA (shRNA) knockdown of CD43 or CD45 expression in Jurkat-Cosmc, HBP-ALL, and CEM T cells decreased HTLV-1 infection severalfold. The knockdown of CD45 in Jurkat cells severely reduced both HTLV-1 and HIV-1 infections, but Cosmc coexpression partially rescued infection. HTLV-1 proteins, which assembled in small patches on Jurkat cells, formed large clusters on the surface of Jurkat-Cosmc cells. These data indicate that large aggregates of HTLV-1 assemblies are more infectious than multiple clustered virions. We suggest that heavily O-glycosylated CD43 and CD45 molecules render cells less adhesive, prevent inappropriate cell-cell contacts, and favor the assembly of HTLV-1 particles into large, highly infectious structures on the surface of T cells.
Core groups, antimicrobial resistance and rebound in gonorrhoea in North America
Authors: Chan Christina H , McCabe Caitlin J , Fisman David N 
Published: December 2011

BackgroundGenital tract infections caused byNeisseria gonorrhoeaeare a major cause of sexually transmitted disease worldwide. Surveillance data suggest that incidence has increased in recent years after initially falling in the face of intensified control efforts.ObjectivesThe authors sought to evaluate the potential contribution of antimicrobial resistance to such rebound and to identify optimal treatment strategies in the face of resistance using a mathematical model of gonorrhoea.MethodsThe authors built risk-structured ‘susceptible–infectious–susceptible’ models with and without the possibility of antibiotic resistance and used these models as a platform for the evaluation of competing plausible treatment strategies, including changing antimicrobial choice when resistance prevalence surpassed fixed thresholds, random assignment of treatment and use of combination antimicrobial therapy.ResultsAbsent antimicrobial resistance, strategies that focus on treatment of highest risk individuals (the so-called core group) result in collapse of disease transmission. When antimicrobial resistance exists, a focus on the core group causes rebound in incidence, with maximal dissemination of antibiotic resistance. Random assignment of antimicrobial treatment class outperformed the use of fixed resistance thresholds with respect to sustained reduction in gonorrhoea prevalence.ConclusionsGonorrhoea control is achievable only when core groups are treated, but treatment of core groups maximises dissemination of antimicrobial-resistant strains. This paradox poses a great dilemma to the control and prevention of gonorrhoea and underlines the need for gonococcal vaccines.
A Human Fab-Based Immunoconjugate Specific for the LMP1 Extracellular Domain Inhibits Nasopharyngeal Carcinoma Growth In Vitro and In Vivo
Authors: Chen Renjie , Zhang Dawei , Mao Yuan , Zhu Jin , Ming Hao , Wen Juan , Ma Jun , Cao Qing , Lin Hong , Tang Qi , Liang Jie , Feng Zhenqing 
Published: December 2011

Abstract
Nasopharyngeal carcinoma (NPC) is a major cause of cancer-related death in Southeast Asia and China. Metastasis and relapse are the primary cause of morbidity and mortality in NPC. Recent evidence suggests that the Epstein–Barr virus latent membrane protein 1 (LMP1) is exclusively expressed in most NPC and is a potential target for biotherapy. In this study, we successfully prepared a novel human antibody Fab (HLEAFab) against LMP1 extracellular domain, which was subsequently conjugated with mitomycin C (MMC), thus forming an immunoconjugate (HLEAFab-MMC). The effects of HLEAFab-MMC on proliferation and apoptosis in NPC cell lines HNE2/LMP1 and the inhibition rate of growth of NPC xenografts in nude mice were examined. The inhibition rate of HNE2/LMP1 cell proliferation was the highest for HLEAFab-MMC (76%) compared with MMC (31%) and HLEAFab (22%) at a concentration of 200 nmol/L and showed dose-dependent fashion. The apoptosis rate of HNE2/LMP1 cell lines was 13.88% in HLEAFab-MMC group, 3.04% in MMC group, 2.78% in HLEAFab group, and 2.10% in negative control group at the same concentration, respectively. In vivo, the inhibition rate of growth of NPC xenografts in nude mice was 55.1% in HLEAFab-MMC group, 26.5% in MMC group, and 5.64% in HLEAFab group. In summary, our findings show that HLEAFab-MMC is a unique immunoconjugate with the potential as a novel therapeutic agent in the treatment of LMP1-expressing NPC. Mol Cancer Ther; 11(3); 594–603. ©2011 AACR.
Analytical Expressions for Doppler Spectra of Scatter from Hydrometeors Observed with a Vertically Directed Radar Beam
Authors: Fang Ming , Doviak Richard J. , Albrecht Bruce A. 
Published: December 2011

Abstract
A generalized expression is derived for the correlation function of signals backscattered from hydrometeors observed with a vertically pointed radar beam in which particle size distribution, turbulence, and mean wind are not homogeneous. This study extends the previous work of Fang and Doviak by including the effects of particle size distribution on the measured Doppler spectrum. It shows the measured Doppler spectrum to be the volumetric mean of the weighted convolution of the normalized Doppler spectra associated with turbulence, mean wind, particle oscillation/wobble, and terminal velocity. Without particle oscillation/wobble, mean wind, and turbulence, the Doppler spectrum is the mirror image of the terminal velocity spectrum under the condition that the second-order effect of finite beamwidth can be ignored. This generalized Doppler spectrum reduces further to a previously derived expression if the particle size distribution, or equivalently reflectivity, is uniform. Provided there is a unique relationship between the particle’s terminal velocity and its effective diameter, the derived equations can be applied to scatterers consisting of ice particles as well as water droplets. This study derives the analytical expression for the Doppler spectrum of mean wind and also shows that if stationary homogeneous turbulence is the only contributor to spectral broadening, then the average of a large number of radar-measured Doppler spectra will be equal to the velocity probability density function of turbulence independent of the angular, range, reflectivity, and weighting functions.
Perseverative negative cognitive processes are associated with depression in people with long-term conditions
Authors: Dickens Chris , Coventry Peter , Khara Angee , Bower Peter , Mansell Warren , Bakerly Nawar Diar 
Published: December 2011

Background: Perseverative negative cognitive processes, such as worry, suppression and avoidance of undesirable thoughts, have been linked to persistence and relapse of depression. Such processes could account for poor treatment response though they have received little research attention in people with long-term conditions (LTCs). Method: We conducted a cross-sectional study to investigate the associations of perseverative negative cognitive processes with depression among medical outpatients with LTCs. In 190 patients, we recorded levels of depression (Hospital Anxiety and Depression Scale), worry (Penn State Worry Questionnaire), suppression (White Bear Suppression Inventory) and avoidance of undesirable thoughts (Acceptance and Action Questionnaire). Associations between these constructs were assessed using linear correlation and logistic regression. Results: Both depression (32%) and anxiety (40%) were common in patients recruited. After controlling for demographic and medical confounders, subjects in the top tertile of worry, suppression and avoidance of undesirable thoughts were 20 (95% CIs, 6.6–58.3), 10 (95% CIs, 3.5–25.9) and 22 (95% CIs, 6.0–80.0) times more likely to have possible depression compared to those in the lowest tertile. Conclusions: Prospective research is required to investigate causal relationships between these constructs, and to assess the potential of psychological interventions that target these processes to improve outcomes in patients with LTCs.
Réduction de la mortalité maternelle : quel rôle pour les matrones ?
Authors: Fournier Pierre 
Published: December 2011

Résumé La mortalité maternelle demeure un problème de santé mondiale majeur pour lequel on enregistre peu ou pas de progrès dans de nombreux pays. La communauté internationale est mobilisée autour de cette question et de nombreuses initiatives sont en cours. Actuellement un débat porte sur le rôle des matrones dans la lutte pour la réduction de la mortalité maternelle. Ces accoucheuses traditionnelles ont précédé toutes les formes d’accouchements assistés par du personnel professionnel de santé. On ne peut pas recommander leur utilisation à large échelle car il n’y a pas suffisamment d’évidence sur leur impact, même après avoir été formées ou recyclées. Leur rôle est établi en ce qui concerne la santé périnatale. Pour les mères, elles peuvent contribuer à améliorer des pratiques de santé durant la grossesse, pendant et après l’accouchement. Alors que certains prônent le recours aux matrones qui ont une légitimité culturelle indéniable, d’autres les considèrent comme un frein à la réduction de la mortalité maternelle. Ce commentaire soutient que la tendance à recourir à leurs services diminue de façon inexorable sous le double effet de l’urbanisation et de l’amélioration de l’accès aux services de santé. Le rôle des matrones là où l’accessibilité aux services de santé est faible ne se discute pas car il n’y a pas d’autres alternatives. La mortalité maternelle persiste dans les pays ou les régions dans lesquelles il y a des inégalités d’accès aux services de santé. Le principe d’équité commande que l’on réduise ces inégalités le plus rapidement possible et cela constitue le seul moyen de faire diminuer la mortalité maternelle à l’échelle mondiale.
Asymmetric segregation and self-renewal of hematopoietic stem and progenitor cells with endocytic Ap2a2
Authors: Ting Stephen B. , Deneault Eric , Hope Kristin , Cellot Sonia , Chagraoui Jalila , Mayotte Nadine , Dorn Jonas F. , Laverdure Jean-Philippe , Harvey Michael , Hawkins Edwin D. , Russell Sarah M. , Maddox Paul S. , Iscove Norman N. , Sauvageau Guy 
Published: December 2011

Abstract
The stem cell–intrinsic model of self-renewal via asymmetric cell division (ACD) posits that fate determinants be partitioned unequally between daughter cells to either activate or suppress the stemness state. ACD is a purported mechanism by which hematopoietic stem cells (HSCs) self-renew, but definitive evidence for this cellular process remains open to conjecture. To address this issue, we chose 73 candidate genes that function within the cell polarity network to identify potential determinants that may concomitantly alter HSC fate while also exhibiting asymmetric segregation at cell division. Initial gene-expression profiles of polarity candidates showed high and differential expression in both HSCs and leukemia stem cells. Altered HSC fate was assessed by our established in vitro to in vivo screen on a subcohort of candidate polarity genes, which revealed 6 novel positive regulators of HSC function: Ap2a2, Gpsm2, Tmod1, Kif3a, Racgap1, and Ccnb1. Interestingly, live-cell videomicroscopy of the endocytic protein AP2A2 shows instances of asymmetric segregation during HSC/progenitor cell cytokinesis. These results contribute further evidence that ACD is functional in HSC self-renewal, suggest a role for Ap2a2 in HSC activity, and provide a unique opportunity to prospectively analyze progeny from HSC asymmetric divisions.
Next generation DNA sequencing technology delivers valuable genetic markers for the genomic orphan legume species, Bituminaria bituminosa
Authors: Pazos-Navarro María , Dabauza Mercedes , Correal Enrique , Hanson Kelly , Teakle Natasha , Real Daniel , Nelson Matthew N 
Published: December 2011

Abstract

Background

Bituminaria bituminosa is a perennial legume species from the Canary Islands and Mediterranean region that has potential as a drought-tolerant pasture species and as a source of pharmaceutical compounds. Three botanical varieties have previously been identified in this species: albomarginata, bituminosa and crassiuscula. B. bituminosa can be considered a genomic 'orphan' species with very few genomic resources available. New DNA sequencing technologies provide an opportunity to develop high quality molecular markers for such orphan species.

Results
432,306 mRNA molecules were sampled from a leaf transcriptome of a single B. bituminosa plant using Roche 454 pyrosequencing, resulting in an average read length of 345 bp (149.1 Mbp in total). Sequences were assembled into 3,838 isotigs/contigs representing putatively unique gene transcripts. Gene ontology descriptors were identified for 3,419 sequences. Raw sequence reads containing simple sequence repeat (SSR) motifs were identified, and 240 primer pairs flanking these motifs were designed. Of 87 primer pairs developed this way, 75 (86.2%) successfully amplified primarily single fragments by PCR. Fragment analysis using 20 primer pairs in 79 accessions of B. bituminosa detected 130 alleles at 21 SSR loci. Genetic diversity analyses confirmed that variation at these SSR loci accurately reflected known taxonomic relationships in original collections of B. bituminosa and provided additional evidence that a division of the botanical variety bituminosa into two according to geographical origin (Mediterranean region and Canary Islands) may be appropriate. Evidence of cross-pollination was also found between botanical varieties within a B. bituminosa breeding programme.

Conclusions

B. bituminosa can no longer be considered a genomic orphan species, having now a large (albeit incomplete) repertoire of expressed gene sequences that can serve as a resource for future genetic studies. This experimental approach was effective in developing codominant and polymorphic SSR markers for application in diverse genetic studies. These markers have already given new insight into genetic variation in B. bituminosa, providing evidence that a division of the botanical variety bituminosa may be appropriate. This approach is commended to those seeking to develop useful markers for genomic orphan species.
Protective effect of probiotics on Salmonella infectivity assessed with combined in vitro gut fermentation-cellular models
Authors: Zihler Annina , Gagnon Mélanie , Chassard Christophe , Lacroix Christophe 
Published: December 2011

Abstract

Background
Accurate assessment of probiotics with targeted anti-Salmonella activity requires suitable models accounting for both, microbe-microbe and host-microbe interactions in gut environments. Here we report the combination of two original in vitro intestinal models closely mimicking the complex in vivo conditions of the large intestine. Effluents from continuous in vitro three-stage fermentation colonic models of Salmonella Typhimurium infection inoculated with immobilized child microbiota and Salmonella were directly applied to confluent mucus-secreting HT29-MTX cell layers. The effects of Salmonella, addition of two bacteriocinogenic strains, Bifidobacterium thermophilum RBL67 (thermophilicin B67) and Escherichia coli L1000 (microcin B17), and inulin were tested on Salmonella growth and interactions with epithelial cell layers. Salmonella adhesion and invasion were investigated and epithelial integrity assessed by transepithelial electrical resistance (TER) measurements and confocal microscopy observation. Data from complex effluents were compared with pure Salmonella cultures.

Results

Salmonella in effluents of all reactors of the colonic fermentation model stabilized at mean values of 5.3 ± 0.8 log10 cfu/ml effluent. Invasion of cell-associated Salmonella was up to 50-fold lower in complex reactor samples compared to pure Salmonella cultures. It further depended on environmental factors, with 0.2 ± 0.1% being measured with proximal, 0.6 ± 0.2% with transverse and 1.3 ± 0.7% with distal reactor effluents, accompanied by a similar high decrease of TER across cell monolayers (minus 45%) and disruption of tight junctions. Subsequent addition of E. coli L1000 stimulated Salmonella growth (6.4 ± 0.6 log10 cfu/ml effluent of all 3 reactors) and further decreased TER, but led to 10-fold decreased invasion efficiency when tested with distal reactor samples. In contrast, presence of B. thermophilum RBL67 revealed a protective effect on epithelial integrity compared to previous E. coli L1000 periods, as reflected by a significant mean increase of TER by 58% in all reactors. Inulin addition enhanced Salmonella growth and invasion when tested with distal and proximal reactor samples, respectively, but induced a limited decrease of TER (minus 18%) in all reactors.

Conclusions
Our results highlight the benefits of combining suitable cellular and colonic fermentation models to assess strain-specific first-level host protection properties of probiotics during Salmonella infection, providing an efficient system biology tool for preclinical development of new antimicrobials.
Comparative analysis of novel and conventional Hsp90 inhibitors on HIF activity and angiogenic potential in clear cell renal cell carcinoma: implications for clinical evaluation
Authors: Bohonowych Jessica ES , Peng Shuping , Gopal Udhayakumar , Hance Michael W , Wing Shane B , Argraves Kelley M , Lundgren Karen , Isaacs Jennifer S 
Published: December 2011

Abstract

Background
Perturbing Hsp90 chaperone function targets hypoxia inducible factor (HIF) function in a von Hippel-Lindau (VHL) independent manner, and represents an approach to combat the contribution of HIF to cell renal carcinoma (CCRCC) progression. However, clinical trials with the prototypic Hsp90 inhibitor 17-AAG have been unsuccessful in halting the progression of advanced CCRCC.

Methods
Here we evaluated a novel next generation small molecule Hsp90 inhibitor, EC154, against HIF isoforms and HIF-driven molecular and functional endpoints. The effects of EC154 were compared to those of the prototypic Hsp90 inhibitor 17-AAG and the histone deacetylase (HDAC) inhibitor LBH589.

Results
The findings indicate that EC154 is a potent inhibitor of HIF, effective at doses 10-fold lower than 17-AAG. While EC154, 17-AAG and the histone deacetylase (HDAC) inhibitor LBH589 impaired HIF transcriptional activity, CCRCC cell motility, and angiogenesis; these effects did not correlate with their ability to diminish HIF protein expression. Further, our results illustrate the complexity of HIF targeting, in that although these agents suppressed HIF transcripts with differential dynamics, these effects were not predictive of drug efficacy in other relevant assays.

Conclusions
We provide evidence for EC154 targeting of HIF in CCRCC and for LBH589 acting as a suppressor of both HIF-1 and HIF-2 activity. We also demonstrate that 17-AAG and EC154, but not LBH589, can restore endothelial barrier function, highlighting a potentially new clinical application for Hsp90 inhibitors. Finally, given the discordance between HIF activity and protein expression, we conclude that HIF expression is not a reliable surrogate for HIF activity. Taken together, our findings emphasize the need to incorporate an integrated approach in evaluating Hsp90 inhibitors within the context of HIF suppression.