bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased vulnerability of rural children on antiretroviral therapy attending public health facilities in South Africa: a retrospective cohort study
Authors: Fatti Geoffrey , Bock Peter , Grimwood Ashraf , Eley Brian 
Published: November 2010

BackgroundA large proportion of the 340,000 HIV‐positive children in South Africa live in rural areas, yet there is little sub‐Saharan data comparing rural paediatric antiretroviral therapy (ART) programme outcomes with urban facilities. We compared clinical, immunological and virological outcomes between children at seven rural and 37 urban facilities across four provinces in South Africa.MethodsWe conducted a retrospective cohort study of routine data of children enrolled on ART between November 2003 and March 2008 in three settings, namely: urban residence and facility attendance (urban group); rural residence and facility attendance (rural group); and rural residents attending urban facilities (rural/urban group). Outcome measures were: death, loss to follow up (LTFU), virological suppression, and changes in CD4 percentage and weight‐for‐age‐z (WAZ) scores. Kaplan‐Meier estimates, logrank tests, multivariable Cox regression and generalized estimating equation models were used to compare outcomes between groups.ResultsIn total, 2332 ART‐naïve children were included, (1727, 228 and 377 children in the urban, rural and rural/urban groups, respectively). At presentation, rural group children were older (6.7 vs. 5.6 and 5.8 years), had lower CD4 cell percentages (10.0% vs. 12.8% and 12.7%), lower WAZ scores (‐2.06 vs. ‐1.46 and ‐1.41) and higher proportions with severe underweight (26% vs.15% and 15%) compared with the urban and rural/urban groups, respectively. Mortality was significantly higher in the rural group and LTFU significantly increased in the rural/urban group. After 24 months of ART, mortality probabilities were 3.4% (CI: 2.4‐4.8%), 7.7% (CI: 4.5‐13.0%) and 3.1% (CI: 1.7‐5.6%) p = 0.0137; LTFU probabilities were 11.5% (CI: 9.3‐14.0%), 8.8% (CI: 4.5‐16.9%) and 16.6% (CI: 12.4‐22.6%), p = 0.0028 in the urban, rural and rural/urban groups, respectively. The rural group had an increased adjusted mortality probability, adjusted hazards ratio 2.41 (CI: 1.25‐4.67) and the rural/urban group had an increased adjusted LTFU probability, aHR 2.85 (CI: 1.41‐5.79). The rural/urban group had a decreased adjusted probability of virological suppression compared with the urban group at any timepoint on treatment, adjusted odds ratio 0.67 (CI: 0.48‐0.93).ConclusionsRural HIV‐positive children are a vulnerable group, exhibiting delayed access to ART and an increased risk of poor outcomes while on ART. Expansion of rural paediatric ART programmes, with future research exploring improvements to rural health system effectiveness, is required.
Systematic detection of putative tumor suppressor genes through the combined use of exome and transcriptome sequencing
Authors: Zhao Qi , Kirkness Ewen F , Caballero Otavia L , Galante Pedro A , Parmigiani Raphael B , Edsall Lee , Kuan Samantha , Ye Zhen , Levy Samuel , Vasconcelos Ana Tereza R , Ren Bing , de Souza Sandro J , Camargo Anamaria A , Simpson Andrew JG , Strausberg Robert L 
Published: November 2010

Abstract
Background
To identify potential tumor suppressor genes, genome-wide data from exome and transcriptome sequencing were combined to search for genes with loss of heterozygosity and allele-specific expression. The analysis was conducted on the breast cancer cell line HCC1954, and a lymphoblast cell line from the same individual, HCC1954BL.

Results
By comparing exome sequences from the two cell lines, we identified loss of heterozygosity events at 403 genes in HCC1954 and at one gene in HCC1954BL. The combination of exome and transcriptome sequence data also revealed 86 and 50 genes with allele specific expression events in HCC1954 and HCC1954BL, which comprise 5.4% and 2.6% of genes surveyed, respectively. Many of these genes identified by loss of heterozygosity and allele-specific expression are known or putative tumor suppressor genes, such as BRCA1, MSH3 and SETX, which participate in DNA repair pathways.

Conclusions
Our results demonstrate that the combined application of high throughput sequencing to exome and allele-specific transcriptome analysis can reveal genes with known tumor suppressor characteristics, and a shortlist of novel candidates for the study of tumor suppressor activities.
Neutrophil IL-10 suppresses peritoneal inflammatory monocytes during polymicrobial sepsis
Authors: Ocuin Lee M , Bamboat Zubin M , Balachandran Vinod P , Cavnar Michael J , Obaid Hebroon , Plitas George , DeMatteo Ronald P 
Published: November 2010

ABSTRACT
Septic peritonitis remains a major cause of death. Neutrophils and inflammatory monocytes are principal components of the innate immune system and are essential for defense against a range of microbial pathogens. Their role and interaction in polymicrobial sepsis have not been defined clearly. Using a murine model of CLP to induce moderate sepsis, we found that neutrophil depletion did not alter survival, whereas depletion of neutrophils and inflammatory monocytes markedly reduced survival. After neutrophil depletion, inflammatory monocytes had greater phagocytic capacity and oxidative burst, and increased expression of costimulatory molecules, TNF, and iNOS. Notably, peritoneal neutrophils produced IL-10 following CLP. Adoptive i.p. transfer of WT but not IL-10−/− neutrophils into septic mice reduced monocyte expression of TNF. In vitro experiments confirmed that monocyte suppression was mediated by neutrophil-derived IL-10. Thus, during septic peritonitis, neutrophils suppress peritoneal inflammatory monocytes through IL-10 and are dispensable for survival.
Glucocorticoids Differentially Regulate the Expression of CRFR1 and CRFR2α in MIN6 Insulinoma Cells and Rodent Islets
Authors: Huising M. O. , Pilbrow A. P. , Matsumoto M. , van der Meulen T. , Park H. , Vaughan J. M. , Lee S. , Vale W. W. 
Published: November 2010

Abstract
Urocortin 3 (Ucn 3), member of the corticotropin-releasing factor (CRF) family of peptide hormones, is released from β-cells to potentiate insulin secretion. Ucn 3 activates the CRF type-2 receptor (CRFR2) but does not activate the type-1 receptor (CRFR1), which was recently demonstrated on β-cells. While the direct actions of Ucn 3 on insulin secretion suggest the presence of cognate receptors within the islet microenvironment, this has not been established. Here we demonstrate that CRFR2α is expressed by MIN6 insulinoma cells and by primary mouse and human islets, with no detectable expression of CRFR2β. Furthermore, stimulation of MIN6 cells or primary mouse islets in vitro or in vivo with glucocorticoids (GCs) robustly and dose-dependently increases the expression of CRFR2α, while simultaneously inhibiting the expression of CRFR1 and incretin receptors. Luciferase reporters driven by the mouse CRFR1 or CRFR2α promoter in MIN6 cells confirm these differential effects of GCs. In contrast, GCs inhibit CRFR2α promoter activity in HEK293 cells and inhibit the expression of CRFR2β in A7r5 rat aortic smooth muscle cells and differentiated C2C12 myotubes. These findings suggest that the GC-mediated increase of CRFR2α depends on the cellular context of the islet and deviates from the GC-mediated suppression of CRFR1 and incretin receptors. Furthermore, GC-induced increases in CRFR2α expression coincide with increased Ucn 3-dependent activation of cAMP and MAPK pathways. We postulate that differential effect of GCs on the expression of CRFR1 and CRFR2α in the endocrine pancreas represent a mechanism to shift sensitivity from CRFR1 to CRFR2 ligands.
11β-Hydroxysteroid Dehydrogenase Type 2 Deficiency Accelerates Atherogenesis and Causes Proinflammatory Changes in the Endothelium in Apoe−/− Mice
Authors: Deuchar Graeme A. , McLean Danielle , Hadoke Patrick W. F. , Brownstein David G. , Webb David J. , Mullins John J. , Chapman Karen , Seckl Jonathan R. , Kotelevtsev Yuri V. 
Published: November 2010

Abstract
Mineralocorticoid receptor (MR) activation is proinflammatory and proatherogenic. Antagonism of MR improves survival in humans with congestive heart failure caused by atherosclerotic disease. In animal models, activation of MR exacerbates atherosclerosis. The enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) prevents inappropriate activation of the MR by inactivating glucocorticoids in mineralocorticoid-target tissues. To determine whether glucocorticoid-mediated activation of MR increases atheromatous plaque formation, we generated Apoe−/−/11β-HSD2−/− double-knockout (E/b2) mice. On chow diet, E/b2 mice developed atherosclerotic lesions by 3 months of age, whereas Apolipoprotein E (Apoe−/−) mice remained lesion free. Brachiocephalic plaques in 3-month-old E/b2 mice showed increased macrophage and lipid content and reduced collagen content compared with similar sized brachiocephalic plaques in 6-month-old Apoe−/− mice. Crucially, treatment of E/b2 mice with eplerenone, an MR antagonist, reduced plaque development and macrophage infiltration while increasing collagen and smooth muscle cell content without any effect on systolic blood pressure. In contrast, reduction of systolic blood pressure in E/b2 mice using the epithelial sodium channel blocker amiloride produced a less-profound atheroprotective effect. Vascular cell adhesion molecule 1 expression was increased in the endothelium of E/b2 mice compared with Apoe−/− mice. Similarly, aldosterone increased vascular cell adhesion molecule 1 expression in mouse aortic endothelial cells, an effect mimicked by corticosterone only in the presence of an 11β-HSD2 inhibitor. Thus, loss of 11β-HSD2 leads to striking atherogenesis associated with activation of MR, stimulating proinflammatory processes in the endothelium of E/b2 mice.
Alendronate for the Treatment of Pediatric Osteogenesis Imperfecta: A Randomized Placebo-Controlled Study
Authors: Ward L. M. , Rauch F. , Whyte M. P. , D'Astous J. , Gates P. E. , Grogan D. , Lester E. L. , McCall R. E. , Pressly T. A. , Sanders J. O. , Smith P. A. , Steiner R. D. , Sullivan E. , Tyerman G. , Smith-Wright D. L. , Verbruggen N. , Heyden N. , Lombardi A. , Glorieux F. H. 
Published: November 2010

abstract

Context:
Information on the use of oral bisphosphonate agents to treat pediatric osteogenesis imperfecta (OI) is limited.

Objective:
The objective of the investigation was to study the efficacy and safety of daily oral alendronate (ALN) in children with OI.

Design and Participants:
We conducted a multicenter, double-blind, randomized, placebo-controlled study. One hundred thirty-nine children (aged 4–19 yr) with type I, III, or IV OI were randomized to either placebo (n = 30) or ALN (n = 109) for 2 yr. ALN doses were 5 mg/d in children less than 40 kg and 10 mg/d for those 40 kg and greater.

Main Outcome Measures:
Spine areal bone mineral density (BMD) z-score, urinary N-telopeptide of collagen type I, extremity fracture incidence, vertebral area, iliac cortical width, bone pain, physical activity, and safety parameters were measured.

Results:
ALN increased spine areal BMD by 51% vs. a 12% increase with placebo (P &lt; 0.001); the mean spine areal BMD z-score increased significantly from −4.6 to −3.3 (P &lt; 0.001) with ALN, whereas the change in the placebo group (from −4.6 to −4.5) was insignificant. Urinary N-telopeptide of collagen type I decreased by 62% in the ALN-treated group, compared with 32% with placebo (P &lt; 0.001). Long-bone fracture incidence, average midline vertebral height, iliac cortical width, bone pain, and physical activity were similar between groups. The incidences of clinical and laboratory adverse experiences were also similar between the treatment and placebo groups.

Conclusions:
Oral ALN for 2 yr in pediatric patients with OI significantly decreased bone turnover and increased spine areal BMD but was not associated with improved fracture outcomes.
High Expression of the Urokinase Plasminogen Activator and Its Cognate Receptor Associates with Advanced Stages and Reduced Disease-Free Interval in Papillary Thyroid Carcinoma
Authors: Ulisse Salvatore , Baldini Enke , Sorrenti Salvatore , Barollo Susi , Gnessi Lucio , Catania Antonio , Pellizzo Maria Rosa , Nardi Francesco , Mian Caterina , De Antoni Enrico , D'Armiento Massimino , Frati Luigi 
Published: November 2010

abstract

Context:
The urokinase plasminogen activating system is implicated in neoplastic progression, and high tissue levels of urokinase plasminogen activating system components correlate with poor prognosis in various human cancers.

Objective:
The objective of the study was to investigate the prognostic relevance of the urokinase plasminogen activator (uPA), its cognate receptor (uPAR), and the plasminogen activator inhibitor 1 (PAI-1) in human papillary thyroid cancer (PTC).

Design:
The expression of uPA, uPAR, and PAI-1 genes was analyzed in PTC and normal matched tissues by quantitative RT-PCR. The case study consisted of 99 patients (21 males and 78 females) affected by PTC including 77 classical, 15 follicular, four tall cell, and three oncocytic variants. Forty-one patients had lymph node metastases at the time of diagnosis. All the patients underwent thyroidectomy and radioiodine therapy followed by thyroid hormone replacement therapy. Follow-up data were available for 76 patients up to 64 months.

Results:
The uPA, uPAR, and PAI-1 mRNA levels were significantly higher in PTC compared with normal matched tissues by 9.63 ± 1,29-, 4.82 ± 0.45-, and 5.64 ± 0.71-fold, respectively. The increased expression of uPA and uPAR correlated statistically with advanced pT and N status. The uPA was also significantly associated with advanced tumor node metastasis stages. The Kaplan-Meier analysis showed a significant association of uPA and uPAR levels with reduced patient disease-free interval (DFI), and this association was stronger in stage I patients.

Conclusion:
The study demonstrated that in PTC the increased gene expression of uPA and uPAR is associated with tumor invasiveness, advanced stages, and shorter DFI, suggesting their prognostic relevance. These observations warrant further investigation in larger patient populations with longer follow-up.
Changes in Placental CRH, Urocortins, and CRH-Receptor mRNA Expression Associated with Preterm Delivery and Chorioamnionitis
Authors: Torricelli Michela , Novembri Romina , Bloise Errico , De Bonis Maria , Challis John R. , Petraglia Felice 
Published: November 2010

abstractContext:The pathogenesis of preterm delivery (PTD) is not clear, although inflammation/infection play a major role. Corticotropin releasing-hormone (CRH) and Urocortins (Ucns) are involved in the pathophysiology of PTD.Objective:This study evaluates trophoblast mRNA expression of CRH, Ucn, Ucn2, Ucn3, and their receptors [CRH-type 1 receptor (CRH-R1), CRH-R2] in infective conditions. To determine whether infection or glucocorticoids contribute to change their placental mRNA expression, the effects of lipopolysaccharide or dexamethasone was evaluated.Design:Placentas were obtained from spontaneous PTD; premature rupture of membranes (pPROM) and pPROM with chorioamnionitis.Setting:Placental specimens were collected from women receiving perinatal care at our Division of Obstetrics and Gynecology.Patients or Other Participants:Pregnant women delivered preterm were enrolled.Interventions:mRNA expression was evaluated by RT-PCR.Main Outcome Measure:Because CRH and Ucns are involved in immunological functions we evaluated their involvement in PTD with or without infection.Results:CRH, Ucn2, and CRH-R1 mRNA expression were higher, while Ucn and CRHR-2 were lower in pPROM with chorioamnionitis than in PTD and pPROM. Ucn3 mRNA expression was lower in pPROM with and without chorioamnionitis than in PTD. The addition of lipopolysaccharide in trophoblast explants decreased Ucn, Ucn3, and CRH-R2 and increased CRH, Ucn2, and CRH-R1 mRNA expression in a dose-dependent manner. Dexamethasone increased CRH and decreased Ucn2 mRNA expression in a dose dependent manner.Conclusions:Our findings showed a significant impact of pPROM with chorioamnionitis on placental CRH peptides and receptors, suggesting that placental expression of stress-related pathways is activated in infective process.
Formation of Amylose–Poly(tetrahydrofuran) Inclusion Complexes in Ionic Liquid Media
Authors: Kaneko Yoshiro , Kyutoku Tsuyoshi , Shimomura Naoyuki , Kadokawa Jun-ichi 
Published: November 2010

Abstract
In this study, we found that amylose–poly(tetrahydrofuran) (PTHF) inclusion complexes were formed when a mixture of amylose with PTHF was stirred in 1-butyl-3-methylimidazolium chloride of an ionic liquid at high temperature under reduced pressure, followed by cooling and precipitation by addition of methanol.
Graphene Nanoplatelets via Exfoliation of Platelet Carbon Nanofibers and Its Electric Double Layer Capacitance
Authors: Sato Jun , Takasu Yoshio , Fukuda Katsutoshi , Sugimoto Wataru 
Published: November 2010

Abstract
Graphite oxide nanoplatelets with thickness of approximately 1 nm were synthesized via exfoliation of platelet carbon nanofibers with average diameter of 150 nm. The lateral size of the graphite oxide nanoplatelets was in accord with the diameter of the parent platelet carbon nanofibers. Subsequent chemical reduction of the graphite oxide nanoplatelets resulted in graphene nanoplatelet aggregates. Specific capacitance of 132 F g−1 in sulfuric acid electrolyte was obtained for the graphene nanoplatelet electrodes, which is about 1.6 times higher than graphene nanosheet aggregates obtained from natural graphite. The capacitive properties are discussed based on the size of the graphene nanoplatelets.
Ceramide synthases in mammalians, worms, and insects: emerging schemes
Authors: Voelzmann André , Bauer Reinhard 
Published: November 2010

AbstractThe ceramide synthase (CerS) gene family comprises a group of highly conserved transmembrane proteins, which are found in all studied eukaryotes. The key feature of the CerS proteins is their role in ceramide synthase activity. Therefore, their original name ‘longevity assurance gene (Lass) homologs’, after the founding member, the yeast longevity assurance genelag1, was altered to ‘CerS’. All CerS have high sequence similarity in a domain called LAG1 motif and a subset of CerS proteins is predicted to contain a Homeobox (Hox) domain. These domains could be the key to the multiple roles CerS have. CerS proteins play a role in diverse biological processes such as proliferation, differentiation, apoptosis, stress response, cancer, and neurodegeneration. In this review, we focus on CerS structure and biological function with emphasis of biological functions in the widely used model systemsCaenorhabditis elegansandDrosophila melanogaster. Also, we focus on the accumulating data suggesting a role for CerS in lipid homeostasis.
The epigenetic regulator Cfp1
Authors: Skalnik David G. 
Published: November 2010

AbstractNumerous epigenetic modifications have been identified and correlated with transcriptionally active euchromatin or repressed heterochromatin and many enzymes responsible for the addition and removal of these marks have been characterized. However, less is known regarding how these enzymes are regulated and targeted to appropriate genomic locations. Mammalian CXXC finger protein 1 is an epigenetic regulator that was originally identified as a protein that binds specifically to any DNA sequence containing an unmethylated CpG dinucleotide. Mouse embryos lacking CXXC finger protein 1 die prior to gastrulation, and embryonic stem cells lacking CXXC finger protein 1 are viable but are unable to achieve cellular differentiation and lineage commitment. CXXC finger protein 1 is a regulator of both cytosine and histone methylation. It physically interacts with DNA methyltransferase 1 and facilitates maintenance cytosine methylation. Rescue studies reveal that CXXC finger protein 1 contains redundant functional domains that are sufficient to support cellular differentiation and proper levels of cytosine methylation. CXXC finger protein 1 is also a component of the Setd1 histone H3-Lys4 methyltransferase complexes and functions to target these enzymes to unmethylated CpG islands. Depletion of CXXC finger protein 1 leads to loss of histone H3-Lys4 tri-methylation at CpG islands and inappropriate drifting of this euchromatin mark into areas of hetero-chromatin. Thus, one function of CXXC finger protein 1 is to serve as an effector protein that interprets cytosine methylation patterns and facilitates crosstalk with histone-modifying enzymes.
Mechanisms of Ion Conduction in Polyelectrolyte Multilayers and Complexes
Authors: Schönhoff Monika , Imre Árpád W. , Bhide Amthra , Cramer Cornelia 
Published: November 2010

Abstract
This paper reviews the progress made in understanding of the mechanisms of ion conduction in polyelectrolyte multilayers (PEM) and polyelectrolyte complexes (PEC). The basis are experimental conductivity data obtained by impedance spectroscopy as a function of relative humidity and temperature, respectively. Mechanically stable thin films of PEM have interesting perspectives as ion conductors, however, being prepared by self-assembly, their stoichiometry and content of ionic charge carriers is unknown. Therefore PEC act as a model material with a variable stoichiometry and known ion content.
Employing poly(sodium 4-styrene sulfonate) (NaPSS) and poly(diallyldimethyl ammoniumchloride) (PDADMAC), we present conductivity spectra of dried polyelectrolyte complexes of type xNaPSS·(1-x)PDADMAC as a function of temperature and composition, respectively. The dependence of the dc conductivity is discussed along with scaling properties of the spectra. The results show that the conductivity is always determined by the sodium ions, even in PEC with an excess of PDADMAC. The ion dynamics and transport mechanisms are, however, different in PDADMAC-rich than in NaPSS-rich PEC.
PEM of different polyionic compounds are investigated in dependence on relative humidity. A general law of an exponential increase of the dc conductivity with relative humidity is found. Absolute values of the conductivity and the strength of the humidity dependence are different for different polyion materials, however, they do not depend on the type of small counterion employed in layer formation. Therefore, it is concluded that in hydrated PEM, protons are the dominant charge carriers.
For both PEM and PEC we show that the MIGRATION concept developed by Funke and co-workers can be used for describing the experimental spectra over wide ranges in frequency. This implies that forward-backward hopping motions of small ions play a vital role in solid polyelectrolyte materials. Apart from these potentially successful hops, localized motions of charged particles are found to influence the conductivity spectra as well.