bluuebunny/crossref_metadata_2025_split huggingface dataset:
White-matter Volume Reduction and the Protective Effect of Immunosuppressive Therapy in Systemic Lupus Erythematosus Patients with Normal Appearance by Conventional Magnetic Resonance Imaging
Authors: XU JIAN , CHENG YUQI , CHAI PEI , LU ZHAOPING , LI HAIJUN , LUO CHUNRONG , LI XIZHI , LI LIN , ZHOU QIXIN , CHEN BING , CAO JUN , XU XIUFENG , SHAN BAOCI , XU LIN , WEN JIANFAN 
Published: March 2010

Objective.The central nervous system (CNS) is often affected by systemic lupus erythematosus (SLE), but assessment of CNS outcomes using noninvasive cerebral structural measures remains in its infancy. Magnetic resonance imaging (MRI) with expert visual interpretation is critical to diagnosis, but does not permit quantitative measurements. Our pilot study investigated whether quantitative brain volumetric analyses could be used to detect white-matter (WM) abnormalities and responses to treatment in SLE (ClinicalTrials.gov: NCT00703742).Methods.Forty-two pairs of SLE patients and healthy controls underwent high-resolution 3-dimensional structural MRI scans. Combining voxel-based morphometry and region of interest analyses, subtle WM volume abnormalities in whole brains from SLE patients were identified, and regional WM volume was calculated. Associations between WM volume and symptom severity, as well as the effects of immunosuppressive therapy, were then investigated.Results.The WM volume of the SLE group was significantly decreased in the bilateral posterior and anterior crus of the internal capsule (PIC and AIC, respectively), the subgyral right frontal lobe, and left temporal lobe (p < 0.001). Regional WM volume (left PIC and right AIC) was correlated with SLEDAI scores. The WM volume of patients treated with immunosuppressive therapy was greater than that of patients who were never treated with immunosuppressive therapy.Conclusion.Quantitative brain volumetric analyses detect brain injuries in WM for SLE that are not obvious by conventional MRI, and may be adequately sensitive and quantitative to measure the effect of therapeutic interventions in preventing brain injury and outcomes in SLE.
Risk Factors for Axial Inflammatory Arthritis in Patients with Psoriatic Arthritis
Authors: CHANDRAN VINOD , TOLUSSO DAVID C. , COOK RICHARD J. , GLADMAN DAFNA D. 
Published: March 2010

Objective.Axial involvement is an important manifestation of psoriatic arthritis (PsA). We aimed to identify risk factors associated with the presence of axial PsA (AxPsA) in patients with PsA.Methods.Patients with AxPsA (bilateral sacroiliitis ≥ grade 2/unilateral sacroiliitis ≥ 3 and inflammatory neck/back pain or limited spinal mobility) at first clinic visit were identified from the University of Toronto PsA clinic database. Risk factors associated with the presence of AxPsA were determined. Subsequently, patients without AxPsA at first clinic visit were identified. Under a multistate framework, the proportion of patients with PsA who subsequently developed AxPsA was estimated robustly using marginal methods and a Markov model. Risk factors at baseline that were associated with future development of AxPsA were identified through multiplicative time-homogeneous Markov models.Results.Our study included 206 patients. Fifty patients had AxPsA at first clinic visit. HLA-B*27, radiographic damage to peripheral joints, and elevated erythrocyte sedimentation rate (ESR) increased odds of having AxPsA, while family history of PsA decreased the odds. One hundred fifty-six patients did not have AxPsA at first clinic visit. On followup, 28 developed AxPsA, and 11 died. We estimated that after 10 years of followup, 15% would develop AxPsA. Nail dystrophy, number of radiographically damaged joints, periostitis, and elevated ESR increased the risk of developing AxPsA, while swollen joints decreased the risk.Conclusion.These results suggest that severe peripheral arthritis and HLA-B*27 are risk factors for AxPsA.
Evidence for Unfolded Protein Response Activation in Monocytes from Individuals with α-1 Antitrypsin Deficiency
Authors: Carroll Tomás P. , Greene Catherine M. , O’Connor Catherine A. , Nolan Áine M. , O’Neill Shane J. , McElvaney Noel G. 
Published: March 2010

Abstract
The hereditary disorder α-1 antitrypsin (AAT) deficiency results from mutations in the SERPINA1 gene and presents with emphysema in young adults and liver disease in childhood. The most common form of AAT deficiency occurs because of the Z mutation, causing the protein to fold aberrantly and accumulate in the endoplasmic reticulum (ER). This leads to ER stress and contributes significantly to the liver disease associated with the condition. In addition to hepatocytes, AAT is also synthesized by monocytes, neutrophils, and epithelial cells. In this study we show for the first time that the unfolded protein response (UPR) is activated in quiescent monocytes from ZZ individuals. Activating transcription factor 4, X-box binding protein 1, and a subset of genes involved in the UPR are increased in monocytes from ZZ compared with MM individuals. This contributes to an inflammatory phenotype with ZZ monocytes exhibiting enhanced cytokine production and activation of the NF-κB pathway when compared with MM monocytes. In addition, we demonstrate intracellular accumulation of AAT within the ER of ZZ monocytes. These are the first data showing that Z AAT protein accumulation induces UPR activation in peripheral blood monocytes. These findings change the current paradigm regarding lung inflammation in AAT deficiency, which up until now was derived from the protease–anti-protease hypothesis, but which now must include the exaggerated inflammatory response generated by accumulated aberrantly folded AAT in circulating blood cells.
Chlamydial Respiratory Infection during Allergen Sensitization Drives Neutrophilic Allergic Airways Disease
Authors: Horvat Jay C. , Starkey Malcolm R. , Kim Richard Y. , Beagley Kenneth W. , Preston Julie A. , Gibson Peter G. , Foster Paul S. , Hansbro Philip M. 
Published: March 2010

Abstract
Neutrophilic asthma is a prevalent, yet recently described phenotype of asthma. It is characterized by neutrophilic rather than eosinophilic airway inflammation and airways hyperresponsiveness (AHR) and may have an infectious origin. Chlamydial respiratory infections are associated with asthma, but how these Th1-inducing bacteria influence Th2-mediated asthma remains unknown. The effects of chlamydial infection on the development of asthma were investigated using a BALB/c mouse model of OVA-induced allergic airways disease (AAD). The effects of current and resolved Chlamydia muridarum infection during OVA sensitization on AAD were assessed and compared with uninfected and nonsensitized controls. Current, but not resolved, infection attenuated hallmark features of AAD: pulmonary eosinophil influx, T cell production of IL-5, mucus-secreting cell hyperplasia, and AHR. Current infection also induced robust OVA-driven neutrophilic inflammation and IFN-γ release from T cells. The phenotype of suppressed but persistent Th2 responses in association with enhanced neutrophilia is reminiscent of neutrophilic asthma. This phenotype was also characterized by increased pulmonary IL-12 and IL-17 expression and activation of APCs, as well as by reduced thymus- and activation-regulated chemokine. Inhibition of pulmonary neutrophil influx during infection blocked OVA-induced neutrophilic inflammation and T cell IFN-γ production and reversed the suppressive effects on mucus-secreting cell hyperplasia and AHR during AAD. These changes correlated with decreased IL-12 and IL-17 expression, increased thymus- and activation-regulated chemokine and altered APC activation. Blocking IFN-γ and IL-17 during OVA challenge had no effect. Thus, active chlamydial respiratory infection during sensitization enhances subsequent neutrophilic inflammation and Th1/Th17 responses during allergen exposure and may have a role in the pathogenesis of neutrophilic asthma.
Differential IL-17 Production and Mannan Recognition Contribute to Fungal Pathogenicity and Commensalism
Authors: Rizzetto Lisa , Kuka Mirela , De Filippo Carlotta , Cambi Alessandra , Netea Mihai G. , Beltrame Luca , Napolitani Giorgio , Torcia Maria Gabriella , D’Oro Ugo , Cavalieri Duccio 
Published: March 2010

Abstract
In this study, we present evidence of differential Th17 responses in human monocyte-derived dendritic cells exposed to the pathogenic Candida albicans or the nonpathogenic Saccharomyces cerevisiae. We use different forms of the microorganisms, cells, hyphae, and spores, as a toolbox to dissect the role of surface mannan in the fungal immune response. In contrast to the S. cerevisiae yeast cell-induced Th1 response, dendritic cells stimulated with spores or C. albicans hyphae induce cellular responses shifted toward Th17 differentiation. The differential recognition of specific mannan structures is the master regulator of the discrimination between harmful and harmless fungi. The switch between spores and yeast is crucial for the commensalism of S. cerevisiae and depends on the use of a different receptor repertoire. Understanding the role of cell wall recognition during infection might lead to understanding the boundaries between safety and pathogenicity.
Unexpected Role for the Immunoproteasome Subunit LMP2 in Antiviral Humoral and Innate Immune Responses
Authors: Hensley Scott E. , Zanker Damien , Dolan Brian P. , David Alexandre , Hickman Heather D. , Embry Alan C. , Skon Cara N. , Grebe Kristie M. , Griffin Thomas A. , Chen Weisan , Bennink Jack R. , Yewdell Jonathan W. 
Published: March 2010

Abstract
Proteasomes are multisubunit proteases that initiate degradation of many Ags presented by MHC class I molecules. Vertebrates express alternate forms of each of the three catalytic proteasome subunits: standard subunits, and immunosubunits, which are constitutively expressed by APCs and are induced in other cell types by exposure to cytokines. The assembly of mixed proteasomes containing standard subunits and immunosubunits is regulated in a tissue specific manner. In this study, we report that the presence of mixed proteasomes in immune cells in LMP2−/− mice compromises multiple components that contribute to the generation of antiviral Ab responses, including splenic B cell numbers, survival and function of adoptively transferred B cells, Th cell function, and dendritic cell secretion of IL-6, TNF-α, IL-1β, and type I IFNs. These defects did not result from compromised overall protein degradation, rather they were associated with altered NF-κB activity. These findings demonstrate an important role for immunoproteasomes in immune cell function beyond their contribution to Ag processing.
IL-17 Promotes p38 MAPK-Dependent Endothelial Activation Enhancing Neutrophil Recruitment to Sites of Inflammation
Authors: Roussel Lucie , Houle François , Chan Carlos , Yao Yu , Bérubé Julie , Olivenstein Ron , Martin James G. , Huot Jacques , Hamid Qutayba , Ferri Lorenzo , Rousseau Simon 
Published: March 2010

Abstract
Neutrophilic inflammation plays an important role in lung tissue destruction occurring in many chronic pulmonary diseases. Neutrophils can be recruited to sites of inflammation via the action of the cytokine IL-17. In this study, we report that IL-17RA and IL-17RC mRNA expression is significantly increased in asthmatic bronchoscopic biopsies and that these receptors are not only expressed on epithelial and inflammatory cells but also on endothelial cells. IL-17 potently stimulates lung microvascular endothelial cells to produce chemoattractants (CXCL8 and derivatives of the 5-lipoxygenase pathway) that selectively drive neutrophil but not lymphocyte chemotaxis. Moreover, IL-17 promotes endothelial activation by inducing the expression of endothelial adhesion markers (E-selectin, VCAM-1, and ICAM-1) in a p38 MAPK-dependent manner. This increased expression of adhesion molecules stimulates the trans-endothelial migration of neutrophils, as well as the transmigration of HT-29 colon carcinoma cells, suggesting a further role in promoting lung metastasis. Finally, IL-17 increased neutrophil adhesion to the endothelium in vivo as determined by intravital microscopy of mice cremaster muscle. Overall, our results demonstrate that IL-17 is a potent activator of the endothelium in vivo leading to neutrophil infiltration. Therefore, preventing neutrophil recruitment by blocking the action of IL-17 on endothelial cells may prove to be highly beneficial in diseases in which neutrophilic inflammation plays a key role.
Peripheral B Cell Tolerance and Function in Transgenic Mice Expressing an IgD Superantigen
Authors: Duong Bao Hoa , Ota Takayuki , Aït-Azzouzene Djemel , Aoki-Ota Miyo , Vela José Luis , Huber Christoph , Walsh Kevin , Gavin Amanda L. , Nemazee David 
Published: March 2010

AbstractTransitional B cells turn over rapidly in vivo and are sensitive to apoptosis upon BCR ligation in vitro. However, little direct evidence addresses their tolerance sensitivity in vivo. A key marker used to distinguish these cells is IgD, which, through alternative RNA splicing of H chain transcripts, begins to be coexpressed with IgM at this stage. IgD is also expressed at high levels on naive follicular (B-2) and at lower levels on marginal zone and B-1 B cells. In this study, mice were generated to ubiquitously express a membrane-bound IgD-superantigen. These mice supported virtually no B-2 development, a greatly reduced marginal zone B cell population, but a relatively normal B-1 compartment. B cell development in the spleen abruptly halted at the transitional B cell population 1 to 2 stage, a block that could not be rescued by either Bcl-2 or BAFF overexpression. The developmentally arrested B cells appeared less mature and turned over more rapidly than nontransgenic T2 cells, exhibiting neither conventional features of anergy nor appreciable receptor editing. Paradoxically, type-2 T-independent responses were more robust in the transgenic mice, although T-dependent responses were reduced and had skewed IgL and IgH isotype usages. Nevertheless, an augmented memory response to secondary challenge was evident. The transgenic mice also had increased serum IgM, but diminished IgG, levels mirrored by the increased numbers of IgM+ plasma cells. This model should facilitate studies of peripheral B cell tolerance, with the advantages of allowing analysis of polyclonal populations, and of B cells naturally lacking IgD.
Chronic Cigarette Smoke Exposure Primes NK Cell Activation in a Mouse Model of Chronic Obstructive Pulmonary Disease
Authors: Motz Gregory T. , Eppert Bryan L. , Wortham Brian W. , Amos-Kroohs Robyn M. , Flury Jennifer L. , Wesselkamper Scott C. , Borchers Michael T. 
Published: March 2010

Abstract
Chronic obstructive pulmonary disease (COPD) is a debilitating, progressive lung disease punctuated by exacerbations of symptoms. COPD exacerbations are most often associated with viral infections, and exposure to cigarette smoke (CS) followed by viral infection has been shown experimentally to enhance lung inflammation, tissue destruction, and airway fibrosis. Despite this, however, the cellular mechanisms responsible for this effect are unknown. In this study, we examined NK cell function in a mouse model of COPD given the vital role of NK cells following viral infection. Ex vivo stimulation of lung leukocytes with poly(I:C), ssRNA40, or ODN1826 enhanced production of NK cell-derived IFN-γ in CS-exposed mice. NK cells from CS-exposed mice exhibited a novel form of priming; highly purified NK cells from CS-exposed mice, relative to NK cells from filtered air-exposed mice, produced more IFN-γ following stimulation with IL-12, IL-18, or both. Further, NK cell priming was lost following smoking cessation. NKG2D stimulation through overexpression of Raet1 on the lung epithelium primed NK cell responsiveness to poly(I:C), ssRNA40, or ODN1826 stimulation, but not cytokine stimulation. In addition, NK cells from CS-exposed mice expressed more cell surface CD107a upon stimulation, demonstrating that the NK cell degranulation response was also primed. Together, these results reveal a novel mechanism of activation of the innate immune system and highlight NK cells as important cellular targets in controlling COPD exacerbations.
Cutting Edge: CD28 and c-Rel–Dependent Pathways Initiate Regulatory T Cell Development
Authors: Vang Kieng B. , Yang Jianying , Pagán Antonio J. , Li Lin-Xi , Wang Junmei , Green Jonathan M. , Beg Amer A. , Farrar Michael A. 
Published: March 2010

Abstract
Regulatory T cell (Treg) development proceeds via a two-step process in which naive CD4+ thymocytes are first converted into CD4+CD25+CD122+GITR+Foxp3− Treg progenitors, followed by a second step in which IL-2 converts these Treg progenitors into CD4+Foxp3+ Tregs. The costimulatory molecule CD28 is required for efficient Treg development. However, the stage at which CD28 affects Treg development remains undefined. In this article, we demonstrate that Cd28−/− mice lack Treg progenitors. Furthermore, the P187YAP motif in the cytoplasmic tail of CD28, which links CD28 to Lck activation, is required for this process. In contrast, the Y170MNM motif, which links CD28 to PI3K activation, is not required for Treg progenitor development. Finally, the CD28/Lck pathway was shown to activate the NF-κB family of transcription factors. We demonstrate that c-Rel, but not NF-κB1, promotes the development of Treg progenitors. Thus, a CD28/c-Rel–dependent pathway is involved in initiating Treg development.
Multiscale variability of the evapotranspiration in eastern Amazonia
Authors: de Sousa Adriano M. L. , Castro Nilza M. R. , Canales Fausto A. , Louzada José A. S. , Vitorino Maria I. , de Souza Everaldo B. 
Published: March 2010

AbstractThis article reports the characteristics of multiple time scales of signals, evapotranspiration (ET) and outgoing long‐wave radiation, in the eastern Amazonia. This has to apply the technique of mathematics Morlet wavelet transform. The results show a difference in the time scales between intraseasonal, synoptic and mesoscale for events. For the non‐flooded event (13 September 2004), hourly fluctuations in ET in scales from 2 to 5 h were more intense than those in the case of the flooded event (9 April 2005). This can be related to mesoscale circulations, possibly caused by local surface conditions, such as Lake Breeze. Copyright © 2010 Royal Meteorological Society
Evolution of Metal Complex‐Catalysts by Dynamic Templating with Transition State Analogs
Authors: Matsumoto Masaomi , Estes Deven , Nicholas Kenneth M. 
Published: March 2010

AbstractThe elicitation of hydrolytic catalysts from a dynamic library of imine‐zinc(II) complexes (and their precursor aldehydes and amines) via templating with pro‐transition state analogs (pro‐TSA) is described. pro‐TSA (2‐pyridyl)phosphonate 2 amplifies a benzimidazole‐derived complex at the expense of an imidazole analogue; the amplified complex is also more active for the hydrolysis of the pyridyl ester 1a. Employing pro‐TSA pyridyl hydrate 3 with libraries of Zn complexes of imines having nucleophilic side chains also perturbs the library in favor of imine‐Zn complexes which prove to be the more active hydrolytic agents and catalysts. The catalytichydrolyses exhibit both saturation kinetics and inhibition by the pro‐TSA. This process for catalyst evolution is operationally simple, amenable to high throughput screening, potentially applicable to a wide variety of catalytic reactions and thus could offer a practical alternative to catalytic antibodies and imprinted polymers.
Fraction of organic carbon predicts labile desorption rates of chlorinated organic pollutants in laboratory-spiked geosorbents
Authors: Ginsbach Jake W. , Killops Kato L. , Olsen Robert M. , Peterson Brittney , Dunnivant Frank M. 
Published: March 2010

Abstract
The resuspension of large volumes of sediments that are contaminated with chlorinated pollutants continues to threaten environmental quality and human health. Whereas kinetic models are more accurate for estimating the environmental impact of these events, their widespread use is substantially hampered by the need for costly, time-consuming, site-specific kinetics experiments. The present study investigated the development of a predictive model for desorption rates from easily measurable sorbent and pollutant properties by examining the relationship between the fraction of organic carbon (fOC) and labile release rates. Duplicate desorption measurements were performed on 46 unique combinations of pollutants and sorbents with fOC values ranging from 0.001 to 0.150. Labile desorption rate constants indicate that release rates predominantly depend upon the fOC in the geosorbent. Previous theoretical models, such as the macro-mesopore and organic matter (MOM) diffusion model, have predicted such a relationship but could not accurately predict the experimental rate constants collected in the present study. An empirical model was successfully developed to correlate the labile desorption rate constant (krap) to the fraction of organic material where log(krap) = 0.291−0.785 · log(fOC). These results provide the first experimental evidence that kinetic pollution releases during resuspension events are governed by the fOC content in natural geosorbents. Environ. Toxicol. Chem. 2010;29:1049–1055. © 2010 SETAC
Fate of trace organic compounds during vadose zone soil treatment in an onsite wastewater system
Authors: Conn Kathleen E. , Siegrist Robert L. , Barber Larry B. , Meyer Michael T. 
Published: March 2010

Abstract
During onsite wastewater treatment, trace organic compounds are often present in the effluents applied to subsurface soils for advanced treatment during vadose zone percolation and groundwater recharge. The fate of the endocrine-disrupting surfactant metabolites 4-nonylphenol (NP), 4-nonylphenolmonoethoxylate (NP1EO), and 4-nonylphenolmonoethoxycarboxylate (NP1EC), metal-chelating agents ethylenediaminetetraacetic acid (EDTA) and nitrilotriacetic acid (NTA), antimicrobial agent triclosan, stimulant caffeine, and antibiotic sulfamethoxazole during transport through an unsaturated sandy loam soil was studied at a field-scale test site. To assess the effects of effluent quality and hydraulic loading rate (HLR) on compound fate in the soil profile, two effluents (septic tank or textile biofilter) were applied at two design HLRs (2 or 8 cm/d). Chemical concentrations were determined in the two effluents and soil pore water at 60, 120, and 240 cm below the soil infiltrative surface. Concentrations of trace organic compounds in septic tank effluent were reduced by more than 90% during transport through 240 cm (often within 60 cm) of soil, likely due to sorption and biotransformation. However, the concentration of NP increased with depth in the shallow soil profile. Additional treatment of anaerobic septic tank effluent with an aerobic textile biofilter reduced effluent concentrations of many compounds, but generally did not affect any changes in pore water concentrations. The soil profile receiving septic tank effluent (vs. textile biofilter effluent) generally had greater percent removal efficiencies. EDTA, NP, NP1EC, and sulfamethoxazole were measured in soil pore water, indicating the ability of some trace organic compounds to reach shallow groundwater. Risk is highly dependent on the degree of further treatment in the saturated zone and the types and proximity of uses for the receiving groundwater environment. Environ. Toxicol. Chem. 2010;29:285–293. © 2009 SETAC