bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sphingosine‐1‐phosphate signaling in physiology and diseases
Authors: Takuwa Yoh , Okamoto Yasuo , Yoshioka Kazuaki , Takuwa Noriko 
Published: June 2012

AbstractSphingosine‐1‐phosphate (S1P), which acts as both the extracellular and intracellular messenger, exerts pleiotropic biological activities including regulation of formation of the vasculature, vascular barrier integrity, and lymphocyte trafficking. Many of these S1P actions are mediated by five members of the G protein‐coupled S1P receptors (S1P1–S1P5) with overlapping but distinct coupling to heterotrimeric G proteins. The biological activities of S1P are based largely on the cellular actions of S1P on migration, adhesion, and proliferation. Notably, S1P often exhibits receptor subtype‐specific, bimodal effects in these cellular actions. For example, S1P1 mediates cell migration toward S1P, that is, chemotaxis, via Gi/Rac pathway whereas S1P2 mediates inhibition of migration toward a chemoattractant, that is, chemorepulsion, via G12/13/Rho pathway, which induces Rac inhibition. In addition, S1P1 mediates stimulation of cell proliferation through the Gi‐mediated signaling pathways including phosphatidylinositol 3‐kinase (PI3K)/Akt and ERK whereas S1P2 mediates inhibition of cell proliferation through mechanisms involving G12/13/Rho/Rho kinase/PTEN‐dependent Akt inhibition. These differential effects of S1P receptor subtypes on migration and proliferation lead to bimodal regulation of various biological responses. An observed biological response is likely determined by an integrated outcome of the counteracting signals input by S1P receptor subtypes. More recent studies identified the new intracellular targets of S1P including the inflammatory signaling molecule TRAF2 and histone deacetylases HDAC1 and HDAC2. These interactions of S1P regulate NF‐κB activity and gene expression, respectively. Development of S1P receptor agonists and antagonists with improved receptor subtype‐selectivity, inhibitors, or modulators of sphingolipid‐metabolizing enzymes, and their optimal drug delivery system provide novel therapeutic tactics. © 2012 International Union of Biochemistry and Molecular Biology, Inc.
Ligand binding by PDZ domains
Authors: Chi Celestine N. , Bach Anders , Strømgaard Kristian , Gianni Stefano , Jemth Per 
Published: June 2012

AbstractThe postsynaptic density protein‐95/disks large/zonula occludens‐1 (PDZ) protein domain family is one of the most common protein–protein interaction modules in mammalian cells, with paralogs present in several hundred human proteins. PDZ domains are found in most cell types, but neuronal proteins, for example, are particularly rich in these domains. The general function of PDZ domains is to bring proteins together within the appropriate cellular compartment, thereby facilitating scaffolding, signaling, and trafficking events. The many functions of PDZ domains under normal physiological as well as pathological conditions have been reviewed recently. In this review, we focus on the molecular details of how PDZ domains bind their protein ligands and their potential as drug targets in this context. © 2012 International Union of Biochemistry and Molecular Biology, Inc.
Free energy calculations of the interactions of c‐Jun‐based synthetic peptides with the c‐Fos protein
Authors: Zuo Zhili , Gandhi Neha S. , Arndt Katja M. , Mancera Ricardo L. 
Published: June 2012

AbstractThe c‐Fos–c‐Jun complex forms the activator protein 1 transcription factor, a therapeutic target in the treatment of cancer. Various synthetic peptides have been designed to try to selectively disrupt the interaction between c‐Fos and c‐Jun at its leucine zipper domain. To evaluate the binding affinity between these synthetic peptides and c‐Fos, polarizable and nonpolarizable molecular dynamics (MD) simulations were conducted, and the resulting conformations were analyzed using the molecular mechanics generalized Born surface area (MM/GBSA) method to compute free energies of binding. In contrast to empirical and semiempirical approaches, the estimation of free energies of binding using a combination of MD simulations and the MM/GBSA approach takes into account dynamical properties such as conformational changes, as well as solvation effects and hydrophobic and hydrophilic interactions. The predicted binding affinities of the series of c‐Jun‐based peptides targeting the c‐Fos peptide show good correlation with experimental melting temperatures. This provides the basis for the rational design of peptides based on internal, van der Waals, and electrostatic interactions. © 2012 Wiley Periodicals, Inc. Biopolymers 97:899–909, 2012.
The impact of influenza hemagglutinin fusion peptide length and viral subtype on its structure and dynamics
Authors: Lorieau Justin L. , Louis John M. , Bax Ad 
Published: June 2012

AbstractA peptide comprising no fewer than the first 20 residues of the influenza hemagglutinin HA2 subunit suffices to induce lipid mixing between the membranes of different unilamellar vesicles. This 20‐residue peptide was previously reported to adopt an open “boomerang” structure that differs significantly from the closed helical‐hairpin structure of a fusion peptide consisting of the first 23 residues of the HA2 sequence. This study investigates the structural and dynamic features of fusion peptides of different length and subtype. Lacking key interactions that stabilize the closed, helical‐hairpin structure, the 20‐residue peptide is in a dynamic equilibrium between closed and open states, adopting a ca. 11% population of the former when solubilized by DPC micelles. Peptides shorter than 20 residues would have even fewer interactions to stabilize a helical hairpin fold, resulting in a vanishing hairpin population. Considering the conserved nature of hairpin‐stabilizing interactions across all serotypes, and the minimum of 20 residues needed for fusion, we postulate that the closed state plays an essential role in the fusion process. However, opening of this hairpin structure may be essential to the formation of a membrane pore at the final stage of the fusion process. Published 2012 Wiley Periodicals, Inc. Biopolymers 99: 189–195, 2013.
The spatiotemporal localization of JAM‐C following sciatic nerve crush in adult rats
Authors: Avari Parizad , Huang Wenlong , Averill Sharon , Colom Bartomeu , Imhof Beat A. , Nourshargh Sussan , Priestley John V. 
Published: June 2012

AbstractJAM‐C is a junctional adhesion molecule, enriched at tight junctions on endothelial and epithelial cells, and also localized to Schwann cells at junctions between adjoining myelin end loops. The role of JAM‐C following peripheral nerve injury (PNI) is currently unknown. We examined the localization of JAM‐C after sciatic nerve crush injury in adult rats. JAM‐C immunoreactivity was present in paranodes and incisures in sham surgery control nerve, but distal to the crush injury significantly decreased at three and 14 days. JAM‐C was re‐expressed at 28 days and, by 56 days, was significantly increased in the distal nerve compared to controls. In a 7‐mm length of sciatic nerve sampled distal to the crush site, the densities of JAM‐C immunoreactive paranodes increased in the distal direction. Conversely, the densities of JAM‐C immunoreactive incisures were highest immediately distal to the crush site and decreased in the more distal direction. Further analysis revealed a strong correlation between JAM‐C localization and remyelination. Fifty‐six days after crush injury, greater densities of JAM‐C paranodes were seen compared to the nodal marker jacalin, suggesting that paranodal JAM‐C precedes node formation. Our data are the first to demonstrate a potential role of JAM‐C in remyelination after PNI.
Exposure to welding fumes increases lung cancer risk among light smokers but not among heavy smokers: evidence from two case–control studies in Montreal
Authors: Vallières Eric , Pintos Javier , Lavoué Jérôme , Parent Marie‐Élise , Rachet Bernard , Siemiatycki Jack 
Published: June 2012

AbstractWe investigated relationships between occupational exposure to gas and arc welding fumes and the risk of lung cancer among workers exposed to these agents throughout the spectrum of industries. Two population‐based case–control studies were conducted in Montreal. Study I (1979–1986) included 857 cases and 1066 controls, and Study II (1996–2001) comprised 736 cases and 894 controls. Detailed job histories were obtained by interview and evaluated by an expert team of chemist–hygienists to estimate degree of exposure to approximately 300 substances for each job. Gas and arc welding fumes were among the agents evaluated. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) of lung cancer using logistic regression, adjusting for smoking history and other covariates. The two studies provided similar results, so a pooled analysis was conducted. Among all subjects, no significant association was found between lung cancer and gas welding fumes (OR = 1.1; 95% CI = 0.9–1.4) or arc welding fumes (OR = 1.0; 95% CI = 0.8–1.2). However, when restricting attention to light smokers, there was an increased risk of lung cancer in relation to gas welding fumes (OR = 2.9; 95% CI = 1.7–4.8) and arc welding fumes (OR = 2.3; 95% CI = 1.3–3.8), with even higher OR estimates among workers with the highest cumulative exposures. In conclusion, there was no detectable excess risk of lung cancer due to welding fumes among moderate to heavy smokers; but among light smokers we found an excess risk related to both types of welding fumes.
Interleukin‐1β mediates metalloproteinase‐dependent renal cell carcinoma tumor cell invasion through the activation of CCAAT enhancer binding protein β
Authors: Petrella Brenda L. , Vincenti Matthew P. 
Published: June 2012

AbstractEffective treatment of metastatic renal cell carcinoma (RCC) remains a major medical concern, as these tumors are refractory to standard therapies and prognosis is poor. Although molecularly targeted therapies have shown some promise in the treatment of this disease, advanced RCC tumors often develop resistance to these drugs. Dissecting the molecular mechanisms underlying the progression to advanced disease is necessary to design alternative and improved treatment strategies. Tumor‐associated macrophages (TAMs) found in aggressive RCC tumors produce a variety of inflammatory cytokines, including interleukin‐1β (IL‐1β). Moreover, the presence of TAMs and high serum levels of IL‐1β in RCC patients correlate with advanced disease. We hypothesized that IL‐1β in the tumor microenvironment promotes the development of aggressive RCC tumors by directing affecting tumor epithelial cells. To address this, we investigated the role of IL‐1β in mediating RCC tumor cell invasion as a measure of tumor progression. We report that IL‐1β induced tumor cell invasion of RCC cells through a process that was dependent on the activity of matrix metalloproteinases (MMPs) and was independent of migration rate. Specifically, IL‐1β induced the expression of MMP‐1, MMP‐3, MMP‐10, and MT1‐MMP in a mechanism dependent on IL‐1β activation of the transcription factor CCAAT enhancer binding protein β (CEBPβ). Consistent with its role in MMP gene expression, CEBPβ knockdown significantly reduced invasion, but not migration, of RCC tumor cells. These results identify the IL‐1β /CEBPβ/MMP pathway as a putative target in the design of anti‐metastatic therapies for the treatment of advanced RCC.
Example‐based inverse kinematics using cage
Authors: Yoshiyasu Yusuke , Yamazaki Nobutoshi 
Published: June 2012

ABSTRACTThis paper presents a cage‐based inverse kinematics (CageIK) that enables interactive posing of character models in a wide range of mesh representations using handle points. By providing a set of cage geometries as examples, CageIK optimizes deformations of the cage according to handle movements and reconstructs the model using a subspace deformation method based on Green Coordinates. CageIK therefore not only poses the model naturally but also preserves details even when leaving the example space. Furthermore, by blending deformations based on bounded biharmonic weights, CageIK can edit the pose of the model locally. Because example cages can be generated from existing models, we can reuse animation assets that were already created by artists or simulations, which avoids repeating the time‐consuming process of creating examples. We show that CageIK can edit a wide variety of models, including multicomponent meshes, polygon soups, and quadrilateral meshes. Copyright © 2012 John Wiley & Sons, Ltd.
Dynamics of cellular automata with input: basis for a systematic study
Authors: Pazienza Giovanni E. , Roska Tamás 
Published: June 2012

ABSTRACTCellular Automata (CA) and related paradigms have been recently revitalized by their practical application to novel computational paradigms. Although numerous aspects of CA have been analyzed throughout the last few decades, little has been done on the CA including an external input, which instead adds dramatically important features to the standard model. In this paper, we propose a methodology to analyze thoroughly and rigorously the CA with input, and provide an accurate simulator for experimental purposes. Copyright © 2012 John Wiley & Sons, Ltd.
The memory support system for mild cognitive impairment: randomized trial of a cognitive rehabilitation intervention
Authors: Greenaway M. C. , Duncan N. L. , Smith G. E. 
Published: June 2012

ObjectiveIndividuals with amnestic mild cognitive impairment (MCI) have few empirically based treatment options for combating their memory loss. This study sought to examine the efficacy of a calendar/notebook rehabilitation intervention, the memory support system (MSS), for individuals with amnestic MCI.MethodsForty individuals with single domain amnestic MCI and their program partners were randomized to receive the MSS, either with training or without (controls). Measures of adherence, activities of daily living, and emotional impact were completed at the first and last intervention sessions and again at 8 weeks and 6 months post intervention.ResultsTraining in use of a notebook/calendar system significantly improved adherence over those who received the calendars but no training. Functional ability and memory self‐efficacy significantly improved for those who received MSS training. Change in functional ability remained significantly better in the intervention group than in the control group out to 8‐week follow‐up. Care partners in the intervention group demonstrated improved mood by 8‐week and 6‐month follow‐ups, whereas control care partners reported worse caregiver burden by 6‐month follow‐up.ConclusionsMemory support system training resulted in improvement in activities of daily living and sense of memory self‐efficacy for individuals with MCI. Although activities of daily living benefits were maintained out to 8 weeks post intervention, future inclusion of booster sessions may help extend the therapeutic effect out even further. Improved mood of care partners of trained individuals and worsening sense of caregiver burden over time for partners of untrained individuals further support the efficacy of the MSS for MCI. Copyright © 2012 John Wiley & Sons, Ltd.
Telephone‐based care management for older adults initiated on psychotropic medication
Authors: Maust Donovan T. , Mavandadi Shahrzad , Benson Amy , Streim Joel E. , DiFilippo Suzanne , Snedden Thomas , Weber Anita L. , Oslin David W. 
Published: June 2012

ObjectiveThis study aimed to explore the longitudinal, 6‐month symptom course of older adults newly started on an antidepressant or anxiolytic by non‐psychiatrist physicians and enrolled in a care management program.MethodThis is a naturalistic cohort study of older adults (age ≥65 years) receiving pharmacotherapy and telephone‐based care management. Participants are non‐institutionalized adults participating in Pennsylvania's Pharmaceutical Assistance Contract for the Elderly who completed telephone‐based clinical assessments including demographic data, self‐report on history of psychiatric treatment and adherence, and standardized symptom scales.ResultsA total of 162 participants with an average age of 77.2 years (SD 6.8) were followed and, for analysis, split into two groups by PHQ‐9 score: 75 (46.3%) scoring 0–4 (minimally symptomatic group, MSG) and 87 (53.7%) scoring ≥5 (symptomatic group, SG). Over 6 months, the SG improved with PHQ‐9 scores beginning on average at 10.0 (SD 4.6) and falling to 5.4 (SD 4.2) (F(1, 86) = 29.53, p < 0.0001). The MSG had no significant change in depressive symptoms. Emotional health as measured by SF‐12 Mental Composite Score mirrored the PHQ‐9 change and lack thereof in the SG and MSG, respectively. No clinical or demographic features were associated with symptom improvement in the SG although they were more likely to report medication adherence (66.7% vs. 44.0%, χ2(1) = 8.4, p = 0.0037) compared with the MSG.ConclusionsParticipation of symptomatic older adults initiated on psychotropic medication in a telephone‐based care management program was associated with improvement in depressive symptoms and overall emotional well‐being, notable findings given participants' advanced age, state‐wide distribution, and history of limited utilization of mental health care. Copyright © 2012 John Wiley & Sons, Ltd.
The provincial health office as performance manager: change in the local healthcare system after Thailand's universal coverage reforms
Authors: Intaranongpai Siranee , Hughes David , Leethongdee Songkramchai 
Published: June 2012

SUMMARYThis paper examines the implementation of Thailand's universal coverage healthcare reforms in a rural province, using data from field studies undertaken in 2003–2005 and 2008–2011. We focus on the strand of policy that aimed to develop primary care by allocating funds to contracting units for primary care (CUPs) responsible for managing local service networks. The two studies document a striking change in the balance of power in the local healthcare system over the 8‐year period. Initially, the newly formed CUPs gained influence as ‘power followed the money’, and the provincial health offices (PHOs), which had commanded the service units, were left with a weaker co‐ordination role. However, the situation changed as a new insurance purchaser, the National Health Security Office, took financial control and established regional outposts. National Health Security Office outposts worked with PHOs to develop rationalised management tools—strategic plans, targets, KPIs and benchmarking—that installed the PHOs as performance managers of local healthcare systems. New lines of accountability and changed budgetary systems reduced the power of the CUPs to control resource allocation and patterns of services within CUP networks. Whereas some CUPs fought to retain limited autonomy, the PHO has been able to regain much of its former control. We suggest that implementation theory needs to take a long view to capture the complexity of a major reform initiative and argue for an analysis that recognises the key role of policy networks and advocacy coalitions that span national and local levels and realign over time. Copyright © 2012 John Wiley & Sons, Ltd.
Using a transient infiltrometric technique for intensively sampling field‐saturated hydraulic conductivity of a clay soil in two runoff plots
Authors: Bagarello V. , Di Stefano C. , Iovino M. , Sgroi A. 
Published: June 2012

AbstractThe point measurement of soil properties allows to explain and simulate plot scale hydrological processes. An intensive sampling was carried out at the surface of an unsaturated clay soil to measure, on two adjacent plots of 4 × 11 m2 and two different dates (May 2007 and February–March 2008), dry soil bulk density, ρb, and antecedent soil water content, θi, at 88 points. Field‐saturated soil hydraulic conductivity, Kfs, was also measured at 176 points by the transient Simplified Falling Head technique to determine the soil water permeability characteristics at the beginning of a possible rainfall event yielding measurable runoff. The ρb values did not differ significantly between the two dates, but wetter soil conditions (by 31%) and lower conductivities (1.95 times) were detected on the second date as compared with the first one. Significantly higher (by a factor of 1.8) Kfs values were obtained with the 0.30‐m‐diameter ring compared with the 0.15‐m‐diameter ring. A high Kfs (> 100 mm h−1) was generally obtained for low θi values (< 0.3 m3m−3), whereas a high θi yielded an increased percentage of low Kfs data (1–100 mm h−1). The median of Kfs for each plot/sampling date combination was not lower than 600 mm h−1, and rainfall intensities rarely exceeded 100 mm h−1 at the site. The occurrence of runoff at the base of the plot needs a substantial reduction of the surface soil permeability characteristics during the event, probably promoted by a higher water content than the one of this investigation (saturation degree = 0.44–0.62) and some soil compaction due to rainfall impact. An intensive soil sampling reduces the risk of an erroneous interpretation of hydrological processes. In an unstable clay soil, changes in Kfs during the event seem to have a noticeable effect on runoff generation, and they should be considered for modeling hydrological processes. Copyright © 2012 John Wiley & Sons, Ltd.
Forest influences on snow accumulation and snowmelt at the Hubbard Brook Experimental Forest, New Hampshire, USA
Authors: Penn Colin A. , Wemple Beverley C. , Campbell John L. 
Published: June 2012

AbstractMany factors influence snow depth, water content and duration in forest ecosystems. The effects of forest cover and canopy gap geometry on snow accumulation has been well documented in coniferous forests of western North America and other regions; however, few studies have evaluated these effects on snowpack dynamics in mixed deciduous forests of the northeastern USA. We measured snow depth and water equivalent near the time of peak snowpack accumulation and, again, during snowmelt to better understand the effect of forests on snowpack properties in the northeastern USA. Surveys occurred in openings and under the forest canopy at plots with different characteristics (e.g. aspect, elevation, forest composition) within the Hubbard Brook Experimental Forest in New Hampshire, USA. Snow water equivalent (SWE) was significantly greater in openings ( p = 0.021) than in forests on north‐facing plots but not on south‐facing plots ( p = 0.318) in early March 2009. One month later, SWE was more variable but remained greater in openings on north‐facing plots ( p = 0.067), whereas SWE was greater ( p = 0.071) under forests than in clearings on south‐facing plots, where snowmelt had sufficiently progressed. During peak accumulation, SWE decreased with increasing conifer cover on north‐facing plots. During the snowmelt period, SWE on south‐facing plots decreased with increasing basal area, sky view factor and diameter at breast height of trees on the plots. These results have implications for spring streamflow and soil moisture in the face of changing climate conditions and land use pressures in the forests of northern New England. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.