bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longer-Term Outcomes of Geriatric Odontoid Fracture Nonunion
Authors: Raudenbush Brandon , Molinari Robert 
Published: July 2015

Introduction: Longer-term outcomes of patients with geriatric type II odontoid fracture nonunion remain unclear. Methods: Thirty-four consecutive geriatric patients (>70 years old) with minimally displaced (<50% displacement) type II odontoid fractures were treated 24 hours a day for 12 weeks with rigid collar immobilization between the years 2003 and 2011. Radiographic and medical record reviews were performed on all 34 patients. Additionally, 7 patients were available for clinical longer-term follow-up (>4 years). Results: In all, 30 (88%) of the 34 patients had nonunion after 12 weeks of treatment, 2 (6%) patients had union, and 2 (6%) patients died during the first 12 weeks. Twenty-one of the 30 patients with nonunion had a displaced or mobile nonunion (70%), and 4 (12%) patients were lost to follow-up. At longer-term follow-up, 23 (68%) patients had died. The average time death occurred was 3.8 years with a range of 0.17 years to 9.42 years postinjury. Twenty of the 23 deaths were attributed to medical comorbidities not related to the patient’s odontoid nonunion. We were unable to determine the cause of death in 3 patients. None of the patients who died had identifiable clinical myelopathy prior to their death on chart review. Of the 7 patients who were alive, all were determined to have odontoid nonunion, of which 5 (70%) were mobile odontoid nonunion. Visual Analog Scale (VAS) and Neck Disability Index (NDI) scores were low (VAS averaged 0.57 and NDI averaged 6.9%) and treatment satisfaction was high (averaged 9.7 of 10). Scores for pain and function did not differ significantly when compared to age-matched controls ( P = .08, t test). Conclusion: Rates of odontoid nonunion are high in patients with geriatric odontoid fractures that are treated with continuous rigid collar for 12 weeks. The majority of patients with nonunion appear to achieve high functional outcomes. In this study, mortality did not appear to be related to adverse neurologic events after treatment.
Targeting glutaminolysis has antileukemic activity in acute myeloid leukemia and synergizes with BCL-2 inhibition
Authors: Jacque Nathalie , Ronchetti Anne Marie , Larrue Clément , Meunier Godelieve , Birsen Rudy , Willems Lise , Saland Estelle , Decroocq Justine , Maciel Thiago Trovati , Lambert Mireille , Poulain Laury , Hospital Marie Anne , Sujobert Pierre , Joseph Laure , Chapuis Nicolas , Lacombe Catherine , Moura Ivan Cruz , Demo Susan , Sarry Jean Emmanuel , Recher Christian , Mayeux Patrick , Tamburini Jérôme , Bouscary Didier 
Published: July 2015

Key Points
Genetic- or compound CB-839–induced GAC inhibition reduces OXPHOS and has antileukemic activity in AML. GAC inhibition synergizes with BCL-2 inhibition by compound ABT-199.
Leukemic marrow infiltration reveals a novel role for Egr3 as a potent inhibitor of normal hematopoietic stem cell proliferation
Authors: Cheng Hui , Hao Sha , Liu Yanfeng , Pang Yakun , Ma Shihui , Dong Fang , Xu Jing , Zheng Guoguang , Li Shaoguang , Yuan Weiping , Cheng Tao 
Published: July 2015

Key Points
Increased quiescence of HSCs and HPCs in leukemogenesis, and reversible suppression of HSCs was observed in leukemic bone marrow. A novel inhibitory role of Egr3 in HSC proliferation was revealed by leukemic infiltration in bone marrow.
The biology of pediatric acute megakaryoblastic leukemia
Authors: Gruber Tanja A. , Downing James R. 
Published: July 2015

Abstract
Acute megakaryoblastic leukemia (AMKL) comprises between 4% and 15% of newly diagnosed pediatric acute myeloid leukemia patients. AMKL in children with Down syndrome (DS) is characterized by a founding GATA1 mutation that cooperates with trisomy 21, followed by the acquisition of additional somatic mutations. In contrast, non–DS-AMKL is characterized by chimeric oncogenes consisting of genes known to play a role in normal hematopoiesis. CBFA2T3-GLIS2 is the most frequent chimeric oncogene identified to date in this subset of patients and confers a poor prognosis.
The TNF-family cytokine TL1A: from lymphocyte costimulator to disease co-conspirator
Authors: Richard Arianne C , Ferdinand John R , Meylan Francoise , Hayes Erika T , Gabay Odile , Siegel Richard M 
Published: July 2015

Abstract
Originally described in 2002 as a T cell-costimulatory cytokine, the tumor necrosis factor family member TNF-like factor 1A (TL1A), encoded by the TNFSF15 gene, has since been found to affect multiple cell lineages through its receptor, death receptor 3 (DR3, encoded by TNFRSF25) with distinct cell-type effects. Genetic deficiency or blockade of TL1A-DR3 has defined a number of disease states that depend on this cytokine-receptor pair, whereas excess TL1A leads to allergic gastrointestinal inflammation through stimulation of group 2 innate lymphoid cells. Noncoding variants in the TL1A locus are associated with susceptibility to inflammatory bowel disease and leprosy, predicting that the level of TL1A expression may influence host defense and the development of autoimmune and inflammatory diseases.
Spatiotemporal dynamics of effector CD8+ T cell responses within the liver
Authors: Inverso Donato , Iannacone Matteo 
Published: July 2015

Abstract
CD8+ T cells play a critical role in controlling hepatotropic viral infections, such as those caused by hepatitis B and hepatitis C viruses. The capacity of these cells to protect against such pathogens is mediated by antigen-experienced effector cells and relies on their ability to home to the liver, recognize pathogen-derived antigens, and deploy effector functions. Here, we review how dynamic imaging of hepatic effector CD8+ T cell migration and function in mouse models of hepatitis B virus pathogenesis has recently revealed a unique and novel mode of adaptive immune surveillance. Circulating effector CD8+ T cells initially arrest within liver sinusoids by docking onto adherent platelets and then actively crawl along the liver vasculature, probing hepatocytes for the presence of antigens by extending protrusions through the fenestrated sinusoidal endothelial cells. Hepatocellular antigen recognition and effector functions occur while CD8+ T cells are still confined to the intravascular space and are inhibited by the pathologic processes that characterize liver fibrosis. A detailed understanding of the spatiotemporal dynamics of effector CD8+ T cells within the liver is important for the rational design of targeted immunotherapeutic approaches for chronic liver infections.
Paradoxical changes in innate immunity in aging: recent progress and new directions
Authors: Montgomery Ruth R , Shaw Albert C 
Published: July 2015

Abstract
Immunosenescence, describing alterations, including decline of immune responses with age, is comprised of inappropriate elevations, decreases, and dysregulated immune responses, leading to more severe consequences of bacterial and viral infections and reduced responses to vaccination. In adaptive immunity, these changes include increased proportions of antigen-experienced B and T cells at the cost of naïve cell populations. Innate immune changes in aging are complex in spanning multiple cell types, activation states, and tissue context. Innate immune responses are dampened in aging, yet there is also a paradoxical increase in certain signaling pathways and cytokine levels. Here, we review recent progress and highlight novel directions for expected advances that can lead the aging field to a new era of discovery that will embrace the complexity of aging in human populations.
Transcriptome of pancreas-specificBmpr1a-deleted islets links to TPH1–5-HT axis
Authors: Jiang Fang-Xu , Mishina Yuji , Baten Akma , Morahan Grant , Harrison Leonard C. 
Published: July 2015

ABSTRACTBone morphogenetic protein (BMP) signaling is crucial for the development and function of numerous organs, but its role on the function of pancreatic islets is not completely clear. To explore this question, we applied the high throughput transcriptomic analyses on the islets isolated from mice with a pancreas-specific deletion of the gene, Bmpr1a, encoding the type 1a BMP receptor. Consistently, these pBmpr1aKO mice had impaired glucose homeostasis at 3 months, and were more severely affected at 12 months of age. These had lower fasting blood insulin concentrations, with reduced expression of several key regulators of β-cell function. Importantly, transcriptomic profiling of 3-month pBmpr1aKO islets and bioinformatic analyses revealed abnormal expression of 203 metabolic genes. Critically among these, the tryptophan hydroxylase 1 gene (Tph1), encoding the rate-limiting enzyme for the production of 5-hydroxytryptamine (5-HT) was the highest over-expressed one. 5-HT is an important regulator of insulin secretion from β cells. Treatment with excess 5-HT inhibited this secretion. Thus our transcriptomic analysis links two highly conserved molecular pathways the BMP signaling and the TPH1–5-HT axis on glucose homeostasis.
Evolutionarily conserved sites in yeast tropomyosin function in cell polarity, transport and contractile ring formation
Authors: Cranz-Mileva Susanne , MacTaggart Brittany , Russell Jacquelyn , Hitchcock-DeGregori Sarah E. 
Published: July 2015

ABSTRACTTropomyosin is a coiled-coil protein that binds and regulates actin filaments. The tropomyosin gene in Schizosaccharomyces pombe, cdc8, is required for formation of actin cables, contractile rings, and polar localization of actin patches. The roles of conserved residues were investigated in gene replacement mutants. The work validates an evolution-based approach to identify tropomyosin functions in living cells and sites of potential interactions with other proteins. A cdc8 mutant with near-normal actin affinity affects patch polarization and vacuole fusion, possibly by affecting Myo52p, a class V myosin, function. The presence of labile residual cell attachments suggests a delay in completion of cell division and redistribution of cell patches following cytokinesis. Another mutant with a mild phenotype is synthetic negative with GFP-fimbrin, inferring involvement of the mutated tropomyosin sites in interaction between the two proteins. Proteins that assemble in the contractile ring region before actin do so in a mutant cdc8 strain that cannot assemble condensed actin rings, yet some cells can divide. Of general significance, LifeAct-GFP negatively affects the actin cytoskeleton, indicating caution in its use as a biomarker for actin filaments.
Cooperation of the BTB-Zinc finger protein, Abrupt, with cytoskeletal regulators inDrosophilaepithelial tumorigenesis
Authors: Turkel Nezaket , Portela Marta , Poon Carole , Li Jason , Brumby Anthony M. , Richardson Helena E. 
Published: July 2015

ABSTRACTThe deregulation of cell polarity or cytoskeletal regulators is a common occurrence in human epithelial cancers. Moreover, there is accumulating evidence in human epithelial cancer that BTB-ZF genes, such as Bcl6 and ZBTB7A, are oncogenic. From our previous studies in the vinegar fly, Drosophila melanogaster, we have identified a cooperative interaction between a mutation in the apico-basal cell polarity regulator Scribble (Scrib) and overexpression of the BTB-ZF protein Abrupt (Ab). Herein, we show that co-expression of ab with actin cytoskeletal regulators, RhoGEF2 or Src64B, in the developing eye-antennal epithelial tissue results in the formation of overgrown amorphous tumours, whereas ab and DRac1 co-expression leads to non-cell autonomous overgrowth. Together with ab, these genes affect the expression of differentiation genes, resulting in tumours locked in a progenitor cell fate. Finally, we show that the expression of two mammalian genes related to ab, Bcl6 and ZBTB7A, which are oncogenes in mammalian epithelial cancers, significantly correlate with the upregulation of cytoskeletal genes or downregulation of apico-basal cell polarity neoplastic tumour suppressor genes in colorectal, lung and other human epithelial cancers. Altogether, this analysis has revealed that upregulation of cytoskeletal regulators cooperate with Abrupt in Drosophila epithelial tumorigenesis, and that high expression of human BTB-ZF genes, Bcl6 and ZBTB7A, shows significant correlations with cytoskeletal and cell polarity gene expression in specific epithelial tumour types. This highlights the need for further investigation of the cooperation between these genes in mammalian systems.
Alveolar Epithelial A2B Adenosine Receptors in Pulmonary Protection during Acute Lung Injury
Authors: Hoegl Sandra , Brodsky Kelley S. , Blackburn Michael R. , Karmouty-Quintana Harry , Zwissler Bernhard , Eltzschig Holger K. 
Published: July 2015

Abstract
Acute lung injury (ALI) is an acute inflammatory lung disease that causes morbidity and mortality in critically ill patients. However, there are many instances where ALI resolves spontaneously through endogenous pathways that help to control excessive lung inflammation. Previous studies have implicated the extracellular signaling molecule adenosine and signaling events through the A2B adenosine receptor in lung protection. In this context, we hypothesized that tissue-specific expression of the A2B adenosine receptor is responsible for the previously described attenuation of ALI. To address this hypothesis, we exposed mice with tissue-specific deletion of Adora2b to ALI, utilizing a two-hit model where intratracheal LPS treatment is followed by injurious mechanical ventilation. Interestingly, a head-to-head comparison of mice with deletion of Adora2b in the myeloid lineage (Adora2bloxP/loxP LysM Cre+), endothelial cells (Adora2bloxP/loxP VE-cadherin Cre+), or alveolar epithelial cells (Adora2bloxP/loxP SPC Cre+) revealed a selective increase in disease susceptibility in Adora2bloxP/loxP SPC Cre+ mice. More detailed analysis of Adora2bloxP/loxP SPC Cre+ mice confirmed elevated lung inflammation and attenuated alveolar fluid clearance. To directly deliver an A2B adenosine receptor–specific agonist to alveolar epithelial cells, we subsequently performed studies with inhaled BAY 60-6583. Indeed, aerosolized BAY 60-6583 treatment was associated with attenuated pulmonary edema, improved histologic lung injury, and dampened lung inflammation. Collectively, these findings suggest that alveolar epithelial A2B adenosine receptor signaling contributes to lung protection, and they implicate inhaled A2B adenosine receptor agonists in ALI treatment.
Copy Number Variations in CTNNA3 and RBFOX1 Associate with Pediatric Food Allergy
Authors: Li Jin , Fung Irene , Glessner Joseph T. , Pandey Rahul , Wei Zhi , Bakay Marina , Mentch Frank D. , Pellegrino Renata , Wang Tiancheng , Kim Cecilia , Hou Cuiping , Wang Fengxiang , Chiavacci Rosetta M. , Thomas Kelly A. , Spergel Jonathan M. , Hakonarson Hakon , Sleiman Patrick M. A. 
Published: July 2015

Abstract
Food allergy is a significant public health concern, especially among children. Previous candidate gene studies suggested a few susceptibility loci for food allergy, but no study investigated the contribution of copy number variations (CNVs) to food allergy on a genome-wide scale. To investigate the genetics of food allergy, we performed CNV assessment using high-resolution genome-wide single nucleotide polymorphism arrays. CNV calls from a total of 357 cases with confirmed food allergy and 3980 controls were analyzed within a discovery cohort, followed by a replication analysis composed of 167 cases and 1573 controls. We identified that CNVs in CTNNA3 were significantly associated with food allergy in both the discovery cohort and the replication cohort. Of particular interest, CTNNA3 CNVs hit exons or intron regions rich in histone marker H3K4Me1. CNVs in a second gene (RBFOX1) showed a significant association (p = 7.35 × 10−5) with food allergy at the genome-wide level in our meta-analysis of the European ancestry cohorts. The presence of these CNVs was confirmed by quantitative PCR. Furthermore, knockdown of CTNNA3 resulted in upregulation of CD63 and CD203c in mononuclear cells upon PMA stimulation, suggesting a role in sensitization to allergen. We uncovered at least two plausible genes harboring CNV loci that are enriched in pediatric patients with food allergies. The novel gene candidates discovered in this study by genome-wide CNV analysis are compelling drug and diagnostic targets for food allergy.
An Inhibitory Role for the Transcription Factor Stat3 in Controlling IL-4 and Bcl6 Expression in Follicular Helper T Cells
Authors: Wu Hao , Xu Lin-Lin , Teuscher Paulla , Liu Hong , Kaplan Mark H. , Dent Alexander L. 
Published: July 2015

Abstract
The transcription factor Bcl6 is required for development of follicular helper T (TFH) cells. Cytokines that activate Stat3 promote Bcl6 expression and TFH cell differentiation. Previous studies with an acute virus infection model showed that TFH cell differentiation was decreased but not blocked in the absence of Stat3. In this study, we further analyzed the role of Stat3 in TFH cells. In Peyer’s patches, we found that compared with wild-type, Stat3-deficient TFH cells developed at a 25% lower rate and expressed increased IFN-γ and IL-4. Whereas Peyer’s patch germinal center B cells developed at normal numbers with Stat3-deficient TFH cells, IgG1 class switching was greatly increased. Following immunization with sheep RBCs, splenic Stat3-deficient TFH cells developed at a slower rate than in control mice, and splenic germinal center B cells were markedly decreased. Stat3-deficient TFH cells developed poorly in a competitive bone marrow chimera environment. Under all conditions tested, Stat3-deficient TFH cells overexpressed both IL-4 and Bcl6, a pattern specific for the TFH cell population. Finally, we found in vitro that repression of IL-4 expression in CD4 T cells by Bcl6 required Stat3 function. Our data indicate that Stat3 can repress the expression of Bcl6 and IL-4 in TFH cells, and that Stat3 regulates the ability of Bcl6 to repress target genes. Overall, we conclude that Stat3 is required to fine-tune the expression of multiple key genes in TFH cells, and that the specific immune environment determines the function of Stat3 in TFH cells.
Noninvasive In Toto Imaging of the Thymus Reveals Heterogeneous Migratory Behavior of Developing T Cells
Authors: Bajoghli Baubak , Kuri Paola , Inoue Daigo , Aghaallaei Narges , Hanelt Marleen , Thumberger Thomas , Rauzi Matteo , Wittbrodt Joachim , Leptin Maria 
Published: July 2015

Abstract
The migration of developing T cells (thymocytes) between distinct thymic microenvironments is crucial for their development. Ex vivo studies of thymus tissue explants suggest two distinct migratory behaviors of thymocytes in the thymus. In the cortex, thymocytes exhibit a stochastic migration, whereas medullary thymocytes show confined migratory behavior. Thus far, it has been difficult to follow all thymocytes in an entire thymus and relate their differentiation steps to their migratory dynamics. To understand the spatial organization of the migratory behavior and development of thymocytes in a fully functional thymus, we developed transgenic reporter lines for the chemokine receptors ccr9a and ccr9b, as well as for rag2, and used them for noninvasive live imaging of the entire thymus in medaka (Oryzias latipes). We found that the expression of these two chemokine receptors in the medaka juvenile thymus defined two spatially distinct subpopulations of thymocytes. Landmark events of T cell development including proliferation, somatic recombination, and thymic selection can be mapped to subregions of the thymus. The migratory behavior of thymocytes within each of the subpopulations is equally heterogeneous, and specific migratory behaviors are not associated with particular domains in the thymus. During the period when thymocytes express rag2 their migratory behavior was more homogeneous. Therefore, the migratory behavior of thymocytes is partly correlated with their developmental stage rather than being defined by their spatial localization.
IgG-Mediated Immune Suppression to Erythrocytes by Polyclonal Antibodies Can Occur in the Absence of Activating or Inhibitory Fcγ Receptors in a Full Mouse Model
Authors: Bernardo Lidice , Yu Honghui , Amash Alaa , Zimring James C. , Lazarus Alan H. 
Published: July 2015

Abstract
Polyclonal anti-D has been used to prevent RhD-negative mothers from becoming immunized against RhD positive fetal erythrocytes, and this mechanism has been referred as Ab or IgG-mediated immune suppression (AMIS). Although anti-D has been highly successful, the inhibitory mechanisms remain poorly understood. Two major theories behind AMIS involve the binding of IgG to activating or inhibitory FcγR, which can induce either erythrocyte clearance or immune inhibition, respectively. In this work, we explored the absolute role of activating and inhibitory FcγR in the AMIS mechanism using the HOD mouse model of RBC immunization. HOD mice contain a RBC-specific recombinant protein composed of hen egg lysozyme (HEL), OVA and human transmembrane Duffy Ag, and erythrocytes from HOD mice can stimulate an immune response to HEL. To assess the contribution of activating and inhibitory FcγR to AMIS, C57BL/6 versus FcRγ-chain−/− or FcγRIIB−/− mice were used as recipients of HOD-RBC alone or together with anti-HEL Abs (i.e., AMIS) and the resulting immune response to HEL evaluated. We show that anti-HEL polyclonal Abs induce the same degree of AMIS effect in mice lacking these IgG binding receptors as compared with wild-type mice. In agreement with this, F(ab′)2 fragments of the AMIS Ab also significantly reduced the Ab response to the HOD cells. In conclusion, successful inhibition of in vivo Ab responses to HOD-RBC by polyclonal IgG can occur independently of activating or inhibitory FcγR involvement. These results may have implications for the understanding of RhD prophylaxis.
Application of headspace single-drop microextraction (HS-SDME) technique in geochemical exploration for petroleum
Authors: Jing Zhao , Qianyong Liang , Yongqiang Xiong , Yun Li , Chenchen Fang 
Published: July 2015

Abstract
All surface geochemical exploration methods for oil and gas are based on the theory that hydrocarbons generated and trapped at depth seep in varying but detectable quantities to the surface, and the main components detected are usually C1 -C5 hydrocarbons. The C1 -C4 hydrocarbons could come from degradation of organic matter by microbial organisms, while the gasoline range hydrocarbons are totally sourced from thermogenic processes. Therefore, the detection of gasoline range hydrocarbons in soils or sediments could be the most direct evidence for hydrocarbon seepage and the method used to detect the C6 -C12 range hydrocarbons could be a useful technique for surface geochemical exploration method for petroleum. However, because the concentration of gasoline range hydrocarbons in the soils or sediments are usually very low, and the present techniques for detecting those hydrocarbons are not adequate, the gasoline range hydrocarbons have seldom been used in surface geochemical exploration for oil and gas. In this study, the headspace single-drop microextraction (HS-SDME) technique coupled with gas chromatography-flame ionization detection (GC-FID) was employed to determine C6 -C12 gasoline range hydrocarbons in well drilling mud sample. The results show that the C6 -C12 hydrocarbons in the samples could be detected by HS-SDME, and the reservoir depth determined by the concentration of C6 -C12 hydrocarbons was the same with the actual petroleum reservoir depth, which indicated further that the HS-SDME method could be used in geochemical exploration for petroleum.