bluuebunny/crossref_metadata_2025 huggingface dataset:
Markers of Monocyte Activation Revealed by Lipidomic Profiling of Arachidonic Acid-Containing Phospholipids
Authors: Balgoma David , Astudillo Alma M. , Pérez-Chacón Gema , Montero Olimpio , Balboa María A. , Balsinde Jesús
Published: February 2010

Stimulated human monocytes undergo an intense trafficking of arachidonic acid (AA) among glycerophospholipidclasses. Using HPLC coupled to electrospray ionization mass spectrometry, we have characterized changes in the levels of AA-containing phospholipid species in human monocytes. In resting cells, AA was found esterified into various molecular species of phosphatidylinositol (PI), choline glycerophospholipids (PCs), and ethanolamine glycerophospholipids (PEs). All major AA-containing PC and PI molecular species decreased in zymosan-stimulated cells; however, no PE molecular species was found to decrease. In contrast, the levels of three AA-containing species increased in zymosan-activated cells compared with resting cells: 1,2-diarachidonyl-glycero-3-phosphoinositol [PI(20:4/20:4)]; 1,2-diarachidonyl-glycero-3-phosphocholine [PC(20:4/20:4)]; and 1-palmitoleoyl-2-arachidonyl-glycero-3-phosphoethanolamine [PE(16:1/20:4)]. PI(20:4/20:4) and PC(20:4/20:4), but not PE(16:1/20:4), also significantly increased when platelet-activating factor or PMA were used instead of zymosan to stimulate the monocytes. Analysis of the pathways involved in the synthesis of these three lipids suggest that PI(20:4/20:4) and PC(20:4/20:4) were produced in a deacylation/reacylation pathway via acyl-CoA synthetase–dependent reactions, whereas PE(16:1/20:4) was generated via a CoA-independent transacylation reaction. Collectively, our results define the increases in PI(20:4/20:4) and PC(20:4/20:4) as lipid metabolic markers of human monocyte activation and establish lipidomics as a powerful tool for cell typing under various experimental conditions.
Melatonin Protects CD4+ T Cells from Activation-Induced Cell Death by Blocking NFAT-Mediated CD95 Ligand Upregulation
Authors: Pedrosa Alziana Moreno da Cunha , Weinlich Ricardo , Mognol Giuliana Patricia , Robbs Bruno Kaufmann , Viola João Paulo de Biaso , Campa Ana , Amarante-Mendes Gustavo Pessini
Published: February 2010

Over the past 20 y, the hormone melatonin was found to be produced in extrapineal sites, including cells of the immune system. Despite the increasing data regarding the biological effects of melatonin on the regulation of the immune system, the effect of this molecule on T cell survival remains largely unknown. Activation-induced cell death plays a critical role in the maintenance of the homeostasis of the immune system by eliminating self-reactive or chronically stimulated T cells. Because activated T cells not only synthesize melatonin but also respond to it, we investigated whether melatonin could modulate activation-induced cell death. We found that melatonin protects human and murine CD4+ T cells from apoptosis by inhibiting CD95 ligand mRNA and protein upregulation in response to TCR/CD3 stimulation. This inhibition is a result of the interference with calmodulin/calcineurin activation of NFAT that prevents the translocation of NFAT to the nucleus. Accordingly, melatonin has no effect on T cells transfected with a constitutively active form of NFAT capable of migrating to the nucleus and transactivating target genes in the absence of calcineurin activity. Our results revealed a novel biochemical pathway that regulates the expression of CD95 ligand and potentially other downstream targets of NFAT activation.
Matrix Metalloproteinase 12-Deficiency Augments Extracellular Matrix Degrading Metalloproteinases and Attenuates IL-13–Dependent Fibrosis
Authors: Madala Satish K. , Pesce John T. , Ramalingam Thirumalai R. , Wilson Mark S. , Minnicozzi Samantha , Cheever Allen W. , Thompson Robert W. , Mentink-Kane Margaret M. , Wynn Thomas A.
Published: February 2010

Infection with the parasitic helminth Schistosoma mansoni causes significant liver fibrosis and extracellular matrix (ECM) remodeling. Matrix metalloproteinases (MMP) are important regulators of the ECM by regulating cellular inflammation, extracellular matrix deposition, and tissue reorganization. MMP12 is a macrophage-secreted elastase that is highly induced in the liver and lung in response to S. mansoni eggs, confirmed by both DNA microarray and real-time PCR analysis. However, the function of MMP12 in chronic helminth-induced inflammation and fibrosis is unclear. In this study, we reveal that MMP12 acts as a potent inducer of inflammation and fibrosis after infection with the helminth parasite S. mansoni. Surprisingly, the reduction in liver and lung fibrosis in MMP12-deficient mice was not associated with significant changes in cytokine, chemokine, TGF-β1, or tissue inhibitors of matrix metalloproteinase expression. Instead, we observed marked increases in MMP2 and MMP13 expression, suggesting that Mmp12 was promoting fibrosis by limiting the expression of specific ECM-degrading MMPs. Interestingly, like MMP12, MMP13 expression was highly dependent on IL-13 and type II–IL-4 receptor signaling. However, in contrast to MMP12, expression of MMP13 was significantly suppressed by the endogenous IL-13 decoy receptor, IL-13Rα2. In the absence of MMP12, expression of IL-13Rα2 was significantly reduced, providing a possible explanation for the increased IL-13-driven MMP13 activity and reduced fibrosis. As such, these data suggest important counter-regulatory roles between MMP12 and ECM-degrading enzymes like MMP2, MMP9, and MMP13 in Th2 cytokine-driven fibrosis.
FoxP3+RORγt+ T Helper Intermediates Display Suppressive Function against Autoimmune Diabetes
Authors: Tartar Danielle M. , VanMorlan Amie M. , Wan Xiaoxiao , Guloglu F. Betul , Jain Renu , Haymaker Cara L. , Ellis Jason S. , Hoeman Christine M. , Cascio Jason A. , Dhakal Mermagya , Oukka Mohamed , Zaghouani Habib
Published: February 2010

Recently, traces of double-positive FoxP3+RORγt+ T cells were identified and viewed as dual programming differentiation intermediates geared toward development into T regulatory or Th17 cells. In this study, we report that FoxP3+RORγt+ intermediates arise in the NOD mouse T cell repertoire prior to inflammation and can be expanded with tolerogen without further differentiation. Furthermore, FoxP3+RORγt+ cells express both CD62L and membrane-bound TGFβ and use the former to traffic to the pancreas and the latter to suppress effector T cells both in vitro and in vivo. The cells perform these functions as FoxP3+RORγt+ intermediates, despite being able to terminally differentiate into either FoxP3+RORγt− T regulatory or FoxP3−RORγt+ Th17 cells on polarization. These previously unrecognized observations extend plasticity to both differentiation and function and indicate that the intermediates are poised to traffic to sites of inflammation and target diverse pathogenic T cells, likely without prior conditioning by effector T cells, thus broadening efficacy against autoimmunity.
The Septic Shock-Associated IL-10 −1082 A > G Polymorphism Mediates Allele-Specific Transcription via Poly(ADP-Ribose) Polymerase 1 in Macrophages Engulfing Apoptotic Cells
Authors: Kang Xiaoyan , Kim Ha-Jeong , Ramirez Michelle , Salameh Sarah , Ma Xiaojing
Published: February 2010

The biallelic IL-10 single nucleotide polymorphism at −1082 of the promoter region linked to individual variation in cytokine inducibility has been strongly implicated in several pathological conditions including the development of, and outcomes in, septic shock during pneumococcal infection, acute respiratory distress syndrome, and cardiac dysfunction. However, the molecular basis of the single nucleotide polymorphism-mediated variable IL-10 production levels has not been explored. In this study, we report that the −1082G > A alleles in the promoter region of the human IL-10 gene physically interact with a nuclear protein in an allele-specific manner that results in different levels of IL-10 transcription. This protein has been identified as poly(ADP-ribose) polymerase 1 (PARP-1). We show that PARP-1 acts as a transcription repressor, and its DNA-binding activity is strongly regulated in macrophages that engulf apoptotic cells but not stimulated with LPS. These findings unveil a novel role of PARP-1 in the regulation of IL-10 production in an allele-dependent way, which determines individual susceptibility to sepsis-induced inflammatory pathology and the immunological sequelae in a physiological process in which clearance of infection-induced apoptotic cells by professional phagocytes triggers the cytokine synthesis.
Expression of Helios, an Ikaros Transcription Factor Family Member, Differentiates Thymic-Derived from Peripherally Induced Foxp3+ T Regulatory Cells
Authors: Thornton Angela M. , Korty Patricia E. , Tran Dat Q. , Wohlfert Elizabeth A. , Murray Patrick E. , Belkaid Yasmine , Shevach Ethan M.
Published: February 2010

Helios, a member of the Ikaros transcription factor family, is preferentially expressed at the mRNA level by regulatory T cells (Treg cells). We evaluated Helios protein expression using a newly generated mAb and demonstrated that it is expressed in all thymocytes at the double negative 2 stage of thymic development. Although Helios was expressed by 100% of CD4+CD8−Foxp3+ thymocytes, its expression in peripheral lymphoid tissues was restricted to a subpopulation (∼70%) of Foxp3+ T cells in mice and humans. Neither mouse nor human naive T cells induced to express Foxp3 in vitro by TCR stimulation in the presence of TGF-β expressed Helios. Ag-specific Foxp3+ T cells induced in vivo by Ag feeding also failed to express Helios. Collectively, these results demonstrate that Helios is potentially a specific marker of thymic-derived Treg cells and raises the possibility that a significant percentage of Foxp3+ Treg cells are generated extrathymically.
A posteriori error controlled local resolution of evolving interfaces for generalized Cahn–Hilliard equations
Authors: Bartels Sören , Müller Rüdiger
Published: February 2010

For equations of generalized Cahn–Hilliard type we present an a posteriori error analysis that is robust with respect to a small interface length scale
γ
. We propose the solution of a fourth order elliptic eigenvalue problem in each time step to gain a fully computable error bound, which only depends polynomially (of low order) on the inverse of
γ
. A posteriori and a priori error bounds for the eigenvalue problem are also derived. In numerical examples we demonstrate that this approach extends the applicability of robust a posteriori error estimation as it removes restrictive conditions on the initial data. Moreover we show that the computation of the principal eigenvalue allows the detection of critical points during the time evolution that limit the validity of the estimate.
Convexity breaking of the free boundary for porous medium equations
Authors: Ishige Kazuhiro , Salani Paolo
Published: February 2010

We investigate the preservation of convexity of the free boundary by the solutions of the porous medium equation. We prove that starting with an initial datum with some kind of suboptimal αconcavity property, the convexity of the positivity set can be lost in a short time.
Mixed ﬁnite element method for electrowetting on dielectric with contact line pinning
Authors: Walker Shawn W. , Bonito Andrea , Nochetto Ricardo H.
Published: February 2010

We present a mixed ﬁnite element method for a model of the ﬂow in a Hele-Shaw cell of 2-D ﬂuid droplets surrounded by air driven by surface tension and actuated by an electric ﬁeld. The application of interest regards a micro-ﬂuidic device called ElectroWetting on Dielectric (EWOD). Our analysis ﬁrst focuses on the time discrete (continuous in space) problem and is presented in a mixed variational framework, which incorporates curvature as a natural boundary condition. The model includes a viscous damping term for interface motion, as well as contact line pinning (sticking of the interface) and is captured in our formulation by a variational inequality. The semi-discrete problem uses a semiimplicit time discretization of curvature. We prove the well-posedness of the semi-discrete problem and fully discrete problem when discretized with iso-parametric ﬁnite elements. We derive a priori error estimates for the space discretization. We also prove the convergence of an Uzawa algorithm for solving the semi-discrete EWOD system with inequality constraint. We conclude with a discussion about experimental orders of convergence.
Hydroxychloroquine treatment in a community‐based cohort of patients with systemic lupus erythematosus
Authors: Schmajuk Gabriela , Yazdany Jinoos , Trupin Laura , Yelin Edward
Published: February 2010

Objective

In recent years hydroxychloroquine (HCQ) has emerged as a key therapy in systemic lupus erythematosus (SLE). We determined the rates of HCQ use in a diverse, community‐based cohort of patients with SLE and identified predictors of current HCQ use.

Methods

Patients were participants in the University of California San Francisco Lupus Outcomes Study, an ongoing longitudinal study of patients with confirmed SLE. We examined the prevalence of HCQ use per person‐year and compared baseline characteristics of users and nonusers, including demographic, socioeconomic, clinical, and health system use variables. Multiple logistic regression with generalized estimating equations was used to evaluate predictors of HCQ use.

Results

A total of 881 patients contributed 3,095 person‐years of data over 4 interview cycles. The prevalence of HCQ use was 55 per 100 person‐years and was constant throughout the observation period. In multivariate models, the odds of HCQ use were nearly doubled among patients receiving their SLE care from a rheumatologist compared with those identifying generalists or nephrologists as their primary sources of SLE care. In addition, patients with shorter disease duration were more likely to use HCQ, even after adjusting for age and other covariates.

Conclusion

In this community‐based cohort of patients, HCQ use was suboptimal. Physician specialty and disease duration were the strongest predictors of HCQ use. Patients who are not using HCQ, those with longer disease duration, and those who see nonrheumatologists for their SLE care should be targeted for quality improvement.
Amyloid load in fat tissue reflects disease severity and predicts survival in amyloidosis
Authors: van Gameren Ingrid I. , Hazenberg Bouke P. C. , Bijzet Johan , Haagsma Elizabeth B. , Vellenga Edo , Posthumus Marcel D. , Jager Pieter L. , van Rijswijk Martin H.
Published: February 2010

Objective

The severity of systemic amyloidosis is thought to be related to the extent of amyloid deposition. We studied whether amyloid load in fat tissue reflects disease severity and predicts survival.

Methods

We studied all consecutive patients with systemic amyloidosis seen between January 1994 and January 2007 in our tertiary referral center. Congo red–stained abdominal fat smears were graded by 2 observers using a validated semiquantitative scoring system. Disease severity was measured by the total number of major organs involved and the extravascular retention of the serum amyloid P component (EVR24). The association of amyloid load in fat tissue with disease severity and overall survival was studied using multiple regression analysis.

Results

Two hundred twenty patients were included in the study (120 with AL amyloidosis, 66 with AA amyloidosis, and 34 with ATTR amyloidosis). Amyloid grade in fat tissue was associated with the number of major organs involved and EVR24. Female sex turned out to be associated with a higher grade of amyloid in fat tissue than male sex. Amyloid grade in fat tissue was an independent predictor of decreased survival, as were heart involvement, the number of organs involved, AA or AL type of amyloid, and age.

Conclusion

The amount of amyloid in subcutaneous fat tissue in systemic amyloidosis reflects disease severity, as measured by the number of organs involved and EVR24, and predicts decreased survival independent of other well‐known factors.
Excess mortality emerges after 10 years in an inception cohort of early rheumatoid arthritis
Authors: Radovits B. J. , Fransen J. , Al Shamma S. , Eijsbouts A. M. , van Riel P. L. C. M. , Laan R. F. J. M.
Published: February 2010

Objective

To investigate mortality rates, causes of death, time trends in mortality, prognostic factors for mortality, and the relationship between disease activity and mortality over a 23‐year period in an inception cohort of rheumatoid arthritis (RA) patients.

Methods

A prospective inception cohort of RA patients diagnosed between January 1985 and October 2007 was followed for up to 23 years after diagnosis. Excess mortality was analyzed by comparing the observed mortality in the RA cohort with the expected mortality based on the general population of The Netherlands, matched for age, sex, and calendar year. Period analysis was used to examine time trends in survival across calendar time. Prognostic factors for mortality and the influence of the time‐varying Disease Activity Score in 28 joints (DAS28) on mortality were analyzed using multivariable Cox proportional hazards models. Causes of death were analyzed.

Results

Of the 1,049 patients in the cohort, 207 patients died. Differences in observed and expected mortality emerged after 10 years of followup. No improvement in survival was noted over calendar time. Significant baseline predictors of survival were sex, age, rheumatoid factor, disability, and comorbidity. Higher levels of DAS28 over time, adjusted for age, were associated with lower survival rates, more so in men (hazard ratio [HR] 1.58, 95% confidence interval [95% CI] 1.35–1.85) than in women (HR 1.21, 95% CI 1.04–1.42).

Conclusion

Excess mortality in RA emerged after 10 years of disease duration. Absolute survival rates have not improved in the last 23 years and a trend toward a widening mortality gap between RA patients and the general population was visible. Higher disease activity levels contribute to premature death in RA patients.
Motivation as a determinant of physical activity in patients with rheumatoid arthritis
Authors: Hurkmans E. J. , Maes S. , de Gucht V. , Knittle K. , Peeters A. J. , Ronday H. K. , Vlieland T. P. M. Vliet
Published: February 2010

Objective

A sufficient level of physical activity is important in reducing the impact of disease in rheumatoid arthritis (RA) patients. According to self‐determination theory, the achievement and maintenance of physical activity is related to goal setting and ownership, which can be supported by health professionals. Our objective was to examine the association between physical activity and the extent to which RA patients 1) believe that physical activity is a goal set by themselves (autonomous regulation) or by others (coerced regulation) and 2) feel supported by rheumatologists (autonomy supportiveness).

Method

A random selection of 643 RA patients from the outpatient clinics of 3 hospitals were sent a postal survey to assess current physical activity level (Short Questionnaire to Assess Health‐Enhancing Physical Activity), regulation style (Treatment Self‐Regulation Questionnaire), and the autonomy supportiveness of their rheumatologists (modified Health Care Climate Questionnaire).

Results

Of the 271 patients (42%) who returned the questionnaire, 178 (66%) were female, their mean ± SD age was 62 ± 14 years, and their mean ± SD disease duration was 10 ± 8 years. Younger age, female sex, higher education level, shorter disease duration, lower disease activity, and a more autonomous regulation were univariately associated with more physical activity. Hierarchical multiple regression analyses demonstrated that younger age and a more autonomous regulation were significantly associated with a higher physical activity level (P = 0.000 and 0.050, respectively).

Conclusion

Regulation style was a significant determinant of physical activity in RA patients. This finding may contribute to further development of interventions to enhance physical activity in RA patients.
Frequent use of the emergency department among persons with systemic lupus erythematosus
Authors: Panopalis Pantelis , Gillis Joann Zell , Yazdany Jinoos , Trupin Laura , Hersh Aimee , Julian Laura , Criswell Lindsey A. , Katz Patricia , Yelin Edward
Published: February 2010

Objective

To describe characteristics of systemic lupus erythematosus (SLE) patients who are frequent users of the emergency department and to identify predictors of frequent emergency department use.

Methods

Data for this study were derived from the University of California, San Francisco Lupus Outcomes Study, a large cohort of persons with SLE who undergo annual structured interviews. Participants were categorized into 1 of 3 levels of emergency department utilization: nonusers (no visits in the preceding year), occasional users, (1–2 visits), and frequent users (≥3 visits). We compared characteristics of the 3 groups and determined predictors of frequent emergency department use (≥3 visits) using multivariate logistic regression, adjusting for a variety of potential confounding covariates.

Results

Of 807 study participants, 499 (62%) had no emergency department visits; 230 (28%) had occasional emergency department visits (1–2 visits); and 78 (10%) had frequent (≥3 visits) emergency department visits. Frequent users were younger, less likely to be employed, and less likely to have completed college. They also had greater disease activity, worse general health status, and more depressive symptoms. Frequent emergency department users were more likely to have Medicaid as their principal insurance. In multivariate logistic regression, older age predicted a lower likelihood of frequent emergency department visits, whereas greater disease activity and having Medicaid insurance predicted a higher likelihood of frequent emergency department visits.

Conclusion

In persons with SLE, greater disease activity and Medicaid insurance are associated with more frequent emergency department use.
Air‐Stable n‐Type Organic Field‐Effect Transistors Based on Carbonyl‐Bridged Bithiazole Derivatives
Authors: Ie Yutaka , Nitani Masashi , Karakawa Makoto , Tada Hirokazu , Aso Yoshio
Published: February 2010

An electronegative conjugated compound composed of a newly designed carbonyl‐bridged bithiazole unit and trifluoroacetyl terminal groups is synthesized as a candidate for air‐stable n‐type organic field‐effect transistor (OFET) materials. Cyclic voltammetry measurements reveal that carbonyl‐bridging contributes both to lowering the lowest unoccupied molecular orbital energy level and to stabilizing the anionic species. X‐ray crystallographic analysis of the compound shows a planar molecular geometry and a dense molecular packing, which is advantageous to electron transport. Through these appropriate electrochemical properties and structures for n‐type semiconductor materials, OFET devices based on this compound show electron mobilities as high as 0.06 cm2 V−1 s−1 with on/off ratios of 106 and threshold voltages of 20 V under vacuum conditions. Furthermore, these devices show the same order of electron mobility under ambient conditions.
Flexible, Stretchable, Transparent Conducting Films Made from Superaligned Carbon Nanotubes
Authors: Feng Chen , Liu Kai , Wu Jeah‐Sheng , Liu Liang , Cheng Jia‐Shyong , Zhang Yuying , Sun Yinghui , Li Qunqing , Fan Shoushan , Jiang Kaili
Published: February 2010

A straightforward roll‐to‐roll process for fabricating flexible and stretchable superaligned carbon nanotube films as transparent conducting films is demonstrated. Practical touch panels assembled by using these carbon nanotube conducting films are superior in flexibility and wearability—and comparable in linearity—to touch panels based on indium tin oxide (ITO) films. After suitable laser trimming and deposition of Ni and Au metal, the carbon nanotube film possesses excellent performance with two typical values of sheet resistances and transmittances (208 Ω □−1, 90% and 24 Ω □−1, 83.4%), which are comparable to ITO films and better than the present carbon nanotube conducting films in literature. The results provide a route to produce transparent conducting films more easily, effectively, and cheaply, an important step for realizing industrial‐scale applications of carbon nanotubes for transparent conducting films.
Hysteresis in Conjugated Polymer Thin Film Transistors Generated by Chain Relaxation
Authors: Yang Neng‐Jye , Liao Chien‐Shiun , Chen Show‐An
Published: February 2010

The hysteresis phenomenon in a polymer thin film transistor (PTFT) with either poly(3‐hexylthiophene), poly(3‐dodecylthiophene), or poly[2‐methoxy‐5‐(2‐ethylhexyloxy)‐1,4‐phenylene vinylene] is investigated over a wide range of temperatures, and found to be generated by the delay in main chain ring distortion with an applied electric field. In the temperature range for side chain relaxation, main chain motion induced by side chain motion already starts such that polarization of the main chain by the applied electric field is permitted but in a limited extent and is not in phase with the variation in electric field. In the main chain relaxation temperature range, the extent of segmental motion increases, which leads to the main chain being more realignable by the applied electric field and thus a reduced hysteresis. After main chain relaxation is complete, the ring can distort more freely and chain segments are able to realign in phase with the applied electric field, which leads to a leveling off of the hysteresis. This investigation shows for first time that the chain relaxation in conjugated polymers is the origin of the hysteresis in PTFT devices.
Angiogenesis and blood vessel stability in inflammatory arthritis
Authors: Kennedy Aisling , Ng Chin Teck , Biniecka Monika , Saber Tajvur , Taylor Cormac , O'Sullivan Jacintha , Veale Douglas J. , Fearon Ursula
Published: February 2010

Objective

To assess blood vessel stability in inflammatory synovial tissue (ST) and to examine neural cell adhesion molecule (NCAM), oxidative DNA damage, and hypoxia in vivo.

Methods

Macroscopic vascularity and ST oxygen levels were determined in vivo in patients with inflammatory arthritis who were undergoing arthroscopy. Vessel maturity/stability was quantified in matched ST samples by dual immunofluorescence staining for factor VIII (FVIII)/α‐smooth muscle actin (α‐SMA). NCAM and 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine (8‐oxodG) were examined by immunohistochemistry. Angiogenesis was assessed in vitro, using human dermal endothelial cells (HDECs) in a Matrigel tube formation assay.

Results

A significant number of immature vessels (showing no pericyte recruitment) was observed in tissue from patients with inflammatory arthritis (P< 0.001), in contrast to osteoarthritic and normal tissue, which showed complete recruitment of pericytes. Low in vivo PO2levels in the inflamed joint (median [range] 22.8 [3.2–54.1] mm Hg) were inversely related to increased macroscopic vascularity (P< 0.04) and increased microscopic expression of FVIII and α‐SMA (P< 0.04 andP< 0.03, respectively). A significant proportion of vessels showed focal expression of NCAM and strong nuclear 8‐oxodG expression, implicating a loss of EC–pericyte contact and increased DNA damage, levels of which were inversely associated with low in vivo PO2(P= 0.04 for each comparison). Circulating cells were completely negative for 8‐oxodG. Exposure of HDEC to 3% O2(reflecting mean ST in vivo measurements) significantly increased EC tube formation (P< 0.05).

Conclusion

Our findings indicate the presence of unstable vessels in inflamed joints associated with hypoxia, incomplete EC–pericyte interactions, and increased DNA damage. These changes may further contribute to persistent hypoxia in the inflamed joint to further drive this unstable microenvironment.
Genome‐wide linkage analysis of quantitative biomarker traits of osteoarthritis in a large, multigenerational extended family
Authors: Chen Hsiang‐Cheng , Kraus Virginia Byers , Li Yi‐Ju , Nelson Sarah , Haynes Carol , Johnson Jessica , Stabler Thomas , Hauser Elizabeth R. , Gregory Simon G. , Kraus William E. , Shah Svati H.
Published: February 2010

Objective

The genetic contributions to the multifactorial disorder osteoarthritis (OA) have been increasingly recognized. The goal of the current study was to use OA‐related biomarkers of severity and disease burden as quantitative traits to identify genetic susceptibility loci for OA.

Methods

In a large multigenerational extended family (n = 350), we measured 5 OA‐related biomarkers: hyaluronan (HA), cartilage oligomeric matrix protein (COMP), N‐propeptide of type IIA collagen (PIIANP), C‐propeptide of type II procollagen (CPII), and type II collagen neoepitope (C2C). Single‐nucleotide polymorphism markers (n = 6,090) covering the whole genome were genotyped using the Illumina HumanLinkage‐12 BeadChip. Variance components analysis, as implemented in the Sequential Oligogenic Linkage Analysis Routines, was used to estimate heritabilities of the quantitative traits and to calculate 2‐point and multipoint logarithm of odds (LOD) scores using a polygenic model.

Results

After adjusting for age and sex, we found that 4 of the 5 biomarkers exhibited significant heritability (PIIANP 0.57, HA 0.49, COMP 0.43, C2C 0.30; P ≤ 0.01 for all). Fourteen of the 19 loci that had multipoint LOD scores of >1.5 were near to or overlapped with previously reported OA susceptibility loci. Four of these loci were identified by more than 1 biomarker. The maximum multipoint LOD scores for the heritable quantitative biomarker traits were 4.3 for PIIANP (chromosome 8p23.2), 3.2 for COMP (chromosome 8q11.1), 2.0 for HA (chromosome 6q16.3), and 2.0 for C2C (chromosome 5q31.2).

Conclusion

Herein, we report the first evidence of genetic susceptibility loci identified by OA‐related biomarkers in an extended family. Our results demonstrate that serum concentrations of PIIANP, HA, COMP, and C2C have substantial heritable components, and using these biomarkers, several genetic loci potentially contributing to the genetic diversity of OA were identified.
Akt1 in murine chondrocytes controls cartilage calcification during endochondral ossification under physiologic and pathologic conditions
Authors: Fukai Atsushi , Kawamura Naohiro , Saito Taku , Oshima Yasushi , Ikeda Toshiyuki , Kugimiya Fumitaka , Higashikawa Akiro , Yano Fumiko , Ogata Naoshi , Nakamura Kozo , Chung Ung‐Il , Kawaguchi Hiroshi
Published: February 2010

Objective

To examine the role of the phosphoinositide‐dependent serine/threonine protein kinase Akt1 in chondrocytes during endochondral ossification.

Methods

Skeletal phenotypes of homozygous Akt1‐deficient (Akt1−/−) mice and their wild‐type littermates were compared in radiologic and histologic analyses. An experimental osteoarthritis (OA) model was created by surgically inducing instability in the knee joints of mice. For functional analyses, we used primary costal and articular chondrocytes from neonatal mice and mouse chondrogenic ATDC5 cells with retroviral overexpression of constitutively active Akt1 or small interfering RNA (siRNA) for Akt1.

Results

Among the Akt isoforms (Akt1, Akt2, and Akt3), Akt1 was the most highly expressed in chondrocytes, and the total level of Akt protein was decreased in Akt1−/−chondrocytes, indicating a dominant role of Akt1. Akt1−/−mice exhibited dwarfism with normal proliferative and hypertrophic zones but suppressed cartilage calcification in the growth plate compared with their wild‐type littermates. In mice with surgically induced OA, calcified osteophyte formation, but not cartilage degradation, was prevented in the Akt1−/−joints. Calcification was significantly suppressed in cultures of Akt1−/−chondrocytes or ATDC5 cells overexpressing siRNA for Akt1 and was enhanced in ATDC5 cells overexpressing constitutively active Akt1. Neither proliferation nor hypertrophic differentiation was affected by the gain or loss of function of Akt1. The expression of ANK and nucleotide pyrophosphatase/phosphodiesterase 1, which accumulate pyrophosphate, a crucial calcification inhibitor, was enhanced by Akt1 deficiency or siRNA for Akt1 and was suppressed by constitutively active Akt1.

Conclusion

Our findings indicate that Akt1 in chondrocytes controls cartilage calcification by inhibiting pyrophosphate during endochondral ossification in skeletal growth and during osteophyte formation in OA.
Autophagy is a protective mechanism in normal cartilage, and its aging‐related loss is linked with cell death and osteoarthritis
Authors: Caramés Beatriz , Taniguchi Noboru , Otsuki Shuhei , Blanco Francisco J. , Lotz Martin
Published: February 2010

Objective

Autophagy is a process for turnover of intracellular organelles and molecules that protects cells during stress responses. We undertook this study to evaluate the potential roles of Unc‐51–like kinase 1 (ULK1), an inducer of autophagy, Beclin1, a regulator of autophagy, and microtubule‐associated protein 1 light chain 3 (LC3), which executes autophagy, in the development of osteoarthritis (OA) and in cartilage cell death.

Methods

Expression of ULK1, Beclin1, and LC3 was analyzed in normal and OA human articular cartilage and in knee joints of mice with aging‐related and surgically induced OA, using immunohistochemistry and Western blotting. Poly(ADP‐ribose) polymerase (PARP) p85 expression was used to determine the correlation between cell death and autophagy.

Results

ULK1, Beclin1, and LC3 were constitutively expressed in normal human articular cartilage. ULK1, Beclin1, and LC3 protein expression was reduced in OA chondrocytes and cartilage, but these 3 proteins were strongly expressed in the OA cell clusters. In mouse knee joints, loss of glycosaminoglycans (GAGs) was observed at ages 9 months and 12 months and in the surgical OA model, 8 weeks after knee destabilization. Expression of ULK1, Beclin1, and LC3 decreased together with GAG loss, while PARP p85 expression was increased.

Conclusion

Autophagy may be a protective or homeostatic mechanism in normal cartilage. In contrast, human OA and aging‐related and surgically induced OA in mice are associated with a reduction and loss of ULK1, Beclin1, and LC3 expression and a related increase in apoptosis. These results suggest that compromised autophagy represents a novel mechanism in the development of OA.
Comparing the scores of hydrological ensemble forecasts issued by two different hydrological models
Authors: Randrianasolo A. , Ramos M. H. , Thirel G. , Andréassian V. , Martin E.
Published: February 2010

A comparative analysis is conducted to assess the quality of streamflow forecasts issued by two different modeling conceptualizations of catchment response, both driven by the same weather ensemble prediction system (PEARP Météo‐France). The two hydrological modeling approaches are the physically based and distributed hydrometeorological model SIM (Météo‐France) and the lumped soil‐moisture‐accounting type rainfall‐runoff model GRP (Cemagref). Discharges are simulated at 211 catchments in France over 17 months. Skill scores are computed for the first 2 days of forecast range. The results suggest good performance of both hydrological models and illustrate the benefit of streamflow data assimilation for ensemble short‐term forecasting. Copyright © 2010 Royal Meteorological Society
A strategy for perturbing surface initial conditions in LAMEPS
Authors: Wang Yong , Kann Alexander , Bellus Martin , Pailleux Jean , Wittmann Christoph
Published: February 2010

The lack or inadequate representation of uncertainties in the surface initial conditions (ICs) affects the quality of ensemble forecast, in particular the near surface temperature and precipitation. In this paper, a strategy for perturbing surface ICs in limited area model ensemble prediction system, noncycling surface breeding (NCSB) is proposed. The strategy combines short‐range surface forecasts driven by perturbed atmospheric forcing and the breeding method for generating the perturbation to surface ICs. NCSB is implemented and tested in Aire Limitée Adaptation dynamique Développement InterNational‐limited area ensemble forecasting (ALADIN‐LAEF). Statistical verification demonstrates that the application of NCSB improves the ALADIN‐LAEF 2m temperature and precipitation forecast. Positive impacts are also obtained for temperature and specific humidity in the lower atmosphere. Copyright © 2010 Royal Meteorological Society
Response repetition as an error‐correction procedure for sight‐word reading: A replication and extension
Authors: Marvin Kendra L. , Rapp John T. , Stenske Michelle T. , Rojas Nairim R. , Swanson Greg J. , Bartlett Sara M.
Published: February 2010

We evaluated the effects of response repetition (RR) as an error‐correction procedure for increasing sight‐word reading for four individuals using a multiple baseline design. The results for each participant showed that correct responding increased following the introduction of the RR procedure. In addition, responding for three of four participants showed evidence of stimulus generalization, response generalization, or both. Likewise, we found that comparable behavior changes were produced when a participant's paraprofessional implemented RR in a typical classroom. These findings are briefly discussed in terms of procedures that promote behavior acquisition and generalization via negative reinforcement. Copyright © 2010 John Wiley & Sons, Ltd.
Effectiveness of a written clinical pathway for enhanced recovery after transthoracic (Ivor Lewis) oesophagectomy
Authors: Munitiz V , Martinez-de-Haro L F , Ortiz A , Ruiz-de-Angulo D , Pastor P , Parrilla P
Published: February 2010

Background

This study assessed the feasibility of a protocol-driven written clinical pathway for multidisciplinary postoperative management after oesophagectomy for oesophageal neoplasia, and examined whether the application of such a protocol could shorten hospital stay and reduce postoperative morbidity and mortality.

Methods

Consecutive patients undergoing transthoracic oesophagectomy for oesophageal neoplasia were divided into those treated between 2003 and 2008 to whom a clinical pathway was applied for postoperative management (group 1), and a control group treated between 1998 and 2002 when no clinical pathway was applied (group 2).

Results

There were 74 patients in each group. Morbidity rates were similar in the two groups: 31 per cent in group 1 and 38 per cent in group 2. There were more pulmonary complications in group 2 (23 versus 14 per cent; P = 0·025). One patient (1 per cent) in group 1 and four (5 per cent) in group 2 died after surgery (P = 0·010). The median (range) length of hospital stay was 9 (5–98) days for group 1 and 13 (8–106) days in group 2 (P = 0·012).

Conclusion

Use of a written clinical pathway in patients undergoing oesophageal resection significantly reduced pulmonary complications, postoperative mortality and hospital stay.
An Assessment of the Spatial Distribution of Polychlorinated Biphenyl Contamination in Turkey
Authors: Gedik Kadir , Imamoğlu Ipek
Published: February 2010

This study summarizes the relevant information regarding the spatial distribution of polychlorinated biphenyls (PCBs) in various environmental (e. g., soil, sediment, air, water) and biological (e. g., fish, mussel, adipose tissue, milk) media in Turkey. The information sources used for this purpose, in addition to the scientific literature, were; official import records, governmental reports on monitoring of organochlorines, and reports prepared by international organizations. PCBs were never produced in Turkey; however they were imported and used within equipment or otherwise. The number of studies conducted on the topic is increasing significantly throughout the years and especially in the last decade. Evidence of PCB pollution was compared with the available background monitoring results from the region and other parts of the world, as well as relevant legislative standards. Overall, the presence of a number of important local PCB contamination sources is indicated as a result of this assessment.
Allatostatin immunoreactivity in the honeybee brain
Authors: Kreissl Sabine , Strasser Christine , Galizia C. Giovanni
Published: February 2010

Information transmission and processing in the brain is achieved through a small family of chemical neurotransmitters and neuromodulators and a very large family of neuropeptides. In order to understand neural networks in the brain it will be necessary, therefore, to understand the connectivity, morphology, and distribution of peptidergic neurons, and to elucidate their function in the brain. In this study we characterize the distribution of substances related to Dip‐allatostatin I in the honeybee brain, which belongs to the allatostatin‐A (AST) peptide family sharing the conserved c‐terminal sequence ‐YXFGL‐NH2. We found about 500 AST‐immunoreactive (ASTir) neurons in the brain, scattered in 18 groups that varied in their precise location across individuals. Almost all areas of the brain were innervated by ASTir fibers. Most ASTir neurites formed networks within functionally distinct areas, e.g., the antennal lobes, the mushroom bodies, or the optic lobes, indicating local functions of the peptide. A small number of very large neurons had widespread arborizations and neurites were found in the corpora cardiaca and in the cervical connectives, suggesting that AST also has global functions. We double‐stained AST and GABA and found that a subset of ASTir neurons were GABA‐immunoreactive (GABAir). Double staining AST with backfills of olfactory receptor neurons or mass fills of neurons in the antennal lobes and in the mushroom bodies allowed a more fine‐grained description of ASTir networks. Together, this first comprehensive description of AST in the bee brain suggests a diverse functional role of AST, including local and global computational tasks. J. Comp. Neurol. 518:1391–1417, 2010. © 2010 Wiley‐Liss, Inc.
Special Issue: Fluid–structure interaction in biomedical applications
Authors: van Loon R. , van de Vosse F. N.
Published: February 2010

The aim of this issue was to bring together computational studies in a variety of research areas, where biological fluids interact with tissue. This resulted in a selection of papers on blood/vessel, blood/valve, air/lung and cell/platelet/blood interaction. Although convergence, robustness and accuracy of the methods involved clearly play an important role in fluid–structure interaction modelling, particular attention is given to the applications. Copyright © 2010 John Wiley & Sons, Ltd.
Dialectic behavioural therapy has an impact on self‐concept clarity and facets of self‐esteem in women with borderline personality disorder
Authors: Roepke Stefan , Schröder‐Abé Michela , Schütz Astrid , Jacob Gitta , Dams Andreas , Vater Aline , Rüter Anke , Merkl Angela , Heuser Isabella , Lammers Claas‐Hinrich
Published: February 2010

Identity disturbance and an unstable sense of self are core criteria of borderline personality disorder (BPD) and significantly contribute to the suffering of the patient. These impairments are hypothesized to be reflected in low self‐esteem and low self‐concept clarity. The objective of this study was to evaluate the impact of an inpatient dialectic behavioral therapy (DBT) programme on self‐esteem and self‐concept clarity. Forty women with BPD were included in the study. Twenty patients were treated with DBT for 12 weeks in an inpatient setting and 20 patients from the waiting list served as controls. Psychometric scales were used to measure different aspects of self‐esteem, self‐concept clarity and general psychopathology. Patients in the treatment group showed significant enhancement in self‐concept clarity compared with those on the waiting list. Further, the scales of global self‐esteem and, more specifically, the facets of self‐esteem self‐regard, social skills and social confidence were enhanced significantly in the intervention group. Additionally, the treatment had a significant impact on basic self‐esteem in this group. On the other hand, the scale of earning self‐esteem was not significantly abased in patients with BPD and did not show significant changes in the intervention group. Our data provide preliminary evidence that DBT has an impact on several facets of self‐esteem and self‐concept clarity, and thus on identity disturbance, in women with BPD. Copyright © 2010 John Wiley & Sons, Ltd.

Key Practitioner Message:

• Self‐concept clarity, which refers to the BPD criterion identity disturbance, and facets of self‐esteem, are impaired in patients with BPD compared with reference data from healthy controls.

• Our study replicates that depressive symptoms and general psychopathology are improved after a 12‐week DBT programme in BPD patients compared with a waiting list.

• The 12‐week inpatient DBT treatment programme shows significant enhancement in self‐concept clarity and facets of self‐esteem compared with the waiting list.

• Thus, in BPD patients, self‐esteem and the diagnostic criteria identity disturbance, captured by self‐concept clarity, can be influenced with short‐term psychotherapy.
Fachgerechte Erstellung von Fugen in Verblendfassaden
Authors: Kanig Martin , Haupt Steffen
Published: February 2010

Für die Erstellung optisch einwandfreier Verblendfassaden mit sachgerecht ausgeführtem Witterungsschutz bietet die Industrie Werktrockenmörtel an, die an die unterschiedlichen Steinqualitäten angepasst wurden. Gute Argumente für die Baustellenpraxis bieten Vormauermörtel, bei denen die Fugengestaltung mit dem Fugenglattstrich “aus einem Guss” erfolgt. Bei Verwendung von speziellen Fugenmörteln ist auch mit nachträglicher Verfugung eine dichte Fuge zu erzielen. Mörteltechnische Optimierungen, die aus zahlreichen Untersuchungen abgeleitet wurden, können die “Härten der Baustellenpraxis” abmindern. Nach wie vor ist aber die Beachtung ausführungstechnischer Hinweise von höchster Bedeutung.

Professional preparation from joints in facades with facing brickwork. For the preparation from optically intact facades with facing brickwork, with a properly functioning weather protection, the mortar industry offers premade dry mortars, which are adapted to the different types of brick qualities. Good arguments for the construction site praxis are achieved by masonry mortars by which the joint design can be done directly in one step. Through the use of special joint mortars you can achieve in a subsequent application a very tight joint. Technical optimizations within the premade mortar products, which have been won on numerous praxis tests, can help to reduce complications on the working site. Nonetheless is extremely important to follow the application notices for a correct application.