bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of Working Memory in Supporting Drivers’ Situation Awareness for Surrounding Traffic
Authors: Johannsdottir Kamilla R. , Herdman Chris M. 
Published: October 2010

Objective: To link working memory to driver situational awareness (SA) for surrounding traffic. Background: Operating a motor vehicle is a complex activity that requires drivers to maintain a high level of SA. Working memory has been conceptually linked to SA; however, the roles of working memory subsystems in supporting driver SA is unclear. Method: Participants drove a simulated vehicle and monitored surrounding traffic while concurrently performing either visuospatial- or phonological-load tasks. Drivers’ SA was indexed as the ability to recall the positions of the surrounding traffic relative to their own vehicle at the end of each trial. Results: In Experiment 1, a visuospatial task interfered with drivers’ ability to recall the positions of traffic located in front of their vehicle. In contrast, a phonological task interfered with drivers’ ability to recall the positions of traffic located behind their vehicle. Experiment 2 confirmed and extended the findings of Experiment 1 with the use of different visuospatial- and phonological-load tasks. Conclusion: Visuospatial and phonological codes play a role in supporting driver SA for traffic located in the forward view and the rear view, respectively. Application: Drivers’ SA for surrounding vehicles is disrupted by concurrent performance on secondary tasks. The development and implementation of new in-cabin communication, navigation, and informational technologies needs to be done with the knowledge that components of drivers’ working memory capacity may be exceeded, thereby compromising driving safety.
Goal setting as an outcome measure: a systematic review
Authors: Hurn Jane , Kneebone Ian , Cropley Mark 
Published: October 2010

Background: Goal achievement has been considered to be an important measure of outcome by clinicians working with patients in physical and neurological rehabilitation settings. This systematic review was undertaken to examine the reliability, validity and sensitivity of goal setting and goal attainment scaling approaches when used with working age and older people. Aims and objectives: To review the reliability, validity and sensitivity of both goal setting and goal attainment scaling when employed as an outcome measure within a physical and neurological working age and older person rehabilitation environment, by examining the research literature covering the 36 years since goal-setting theory was proposed. Methods: Data sources included a computer-aided literature search of published studies examining the reliability, validity and sensitivity of goal setting/goal attainment scaling, with further references sourced from articles obtained through this process. Main findings: There is strong evidence for the reliability, validity and sensitivity of goal attainment scaling. Empirical support was found for the validity of goal setting but research demonstrating its reliability and sensitivity is limited. Conclusions: Goal attainment scaling appears to be a sound measure for use in physical rehabilitation settings with working age and older people. Further work needs to be carried out with goal setting to establish its reliability and sensitivity as a measurement tool.
BDNF and CGRP interaction: Implications in migraine susceptibility
Authors: Lemos Carolina , Mendonça Denisa , Pereira-Monteiro José , Barros José , Sequeiros Jorge , Alonso Isabel , Sousa Alda 
Published: October 2010

Objectives: Migraine pathophysiology involves several pathways. Our aims were to explore a possible role of the brain-derived neurotrophic factor gene ( BDNF) in migraine susceptibility; to study, for the first time, the calcitonin gene-related peptide gene ( CGRP); and a possible interaction between the two. Methods: Using a case-control approach, four tagging single nucleotide polymorphisms (SNPs) (rs7124442, rs6265, rs11030107, and rs2049046) of BDNF and one tagging SNP—rs1553005—of CGRP were analyzed in 188 cases and 287 controls. A multivariable logistic regression was performed, adjusting for gender. Allelic and haplotypic frequencies were estimated. Interaction was assessed by a stepwise multivariable-logistic regression and confirmed by a multifactor dimensionality reduction analysis. Results: No significant main effects were found; however, a significant interaction was found between BDNF and CGRP, showing an increased risk for the AT-genotype of rs2049046 and the GC-genotype of rs1553005 (odds ratio = 1.88, 95% confidence interval: 1.20–2.93) for migraineurs. Conclusion: Our data support the hypothesis of an interaction between BDNF and CGRP in migraine susceptibility that should be further explored.
Microfracture in the Ankle
Authors: Domayer S.E. , Welsch G.H. , Stelzeneder D. , Hirschfeld C. , Quirbach S. , Nehrer S. , Dorotka R. , Mamisch T.C. , Trattnig S. 
Published: October 2010

Background: Microfracture (MFX) is frequently used to treat deep cartilage defects in the ankle; however, the data on repair tissue (RT) quality after MFX are very limited at this time. T2-mapping at 3 T has been optimized for the ankle and can be used to noninvasively evaluate cartilage collagen and water content. The aim of this study was to determine if the RT after MFX in the ankle had T2 properties similar to the adjacent reference cartilage (RC). Methods: Fourteen cases after MFX in the ankle were assessed with morphological MRI and T2-mapping at 3 T. The American Orthopaedic Foot and Ankle Society (AOFAS) score and a modified Cinicinnati Knee Rating System rating were used to evaluate the clinical outcome. The MRI protocol included a 3-dimensional sequence and a proton-density sequence for morphological evaluation and a multiecho spin echo sequence for T2-mapping. Region of interest analyses were carried out in accordance with the morphological images to ensure complete coverage of the defect site. Results: Both clinical scores demonstrated significant improvement at the time of the MR examination ( P < 0.001). RT T2 was 49.3 ± 10.1 (range, 35.7-69.3) milliseconds, and RC T2 was 49.9 ± 8.2 (range, 38.4-63.7) milliseconds ( P = 0.838). Relative T2 (rT2) was 1.00 ± 0.20 (range, 0.72-1.36). Conclusion: MFX in the ankle can provide RT with T2 properties similar to adjacent cartilage.
Radiological Assessment of Accelerated versus Traditional Approaches to Postoperative Rehabilitation following Matrix-Induced Autologous Chondrocyte Implantation
Authors: Ebert Jay R. , Fallon Michael , Robertson William B. , Lloyd David G. , Zheng M.H. , Wood David J. , Ackland Timothy 
Published: October 2010

Objective: To assess the safety and efficacy of accelerated compared with traditional postoperative weightbearing (WB) rehabilitation following matrix-induced autologous chondrocyte implantation (MACI) of the knee, using MRI. Methods: A randomized controlled study design was used to assess MRI-based outcomes of MACI grafts in 70 patients (45 men, 25 women) who underwent MACI to the medial or lateral femoral condyle, in combination with either traditional or accelerated approaches to postoperative WB rehabilitation. High-resolution MRI was undertaken and assessed 8 previously defined pertinent parameters of graft repair, as well as a combined MRI composite score at 3, 12, and 24 months postsurgery. The association between clinical and MRI-based outcomes, patient demographics, chondral defect parameters, and injury/surgery history was investigated. Results: Both groups significantly improved ( P < 0.05) in the MRI composite score and pertinent descriptors of graft repair throughout the postoperative period until 24 months postsurgery. There were no differences ( P > 0.05) observed between the 2 groups. Patient age, body mass index, chondral defect size, and duration of preoperative symptoms were significantly correlated ( P < 0.05) with several MRI-based outcomes at 24 months, whereas there were no significant pertinent correlations ( P > 0.05) observed between clinical and MRI-based outcomes. Conclusion: The accelerated WB approach was not detrimental to graft development at any stage throughout the postoperative assessment timeline from baseline to 24 months postsurgery and may potentially accelerate patient return to normal function, while reducing postoperative muscle loss, intra-articular adhesions, and associated gait abnormalities.
Effects of Hydrostatic Loading on a Self-Aggregating, Suspension Culture–Derived Cartilage Tissue Analog
Authors: Kraft Jeffrey J. , Jeong Changhoon , Novotny John E. , Seacrist Thomas , Chan Gilbert , Domzalski Marcin , Turka Christina M. , Richardson Dean W. , Dodge George R. 
Published: October 2010

Objective: Many approaches are being taken to generate cartilage replacement materials. The goal of this study was to use a self-aggregating suspension culture model of chondrocytes with mechanical preconditioning. Design: Our model differs from others in that it is based on a scaffold-less, self-aggregating culture model that produces a cartilage tissue analog that has been shown to share many similarities with the natural cartilage phenotype. Owing to the known loaded environment under which chondrocytes function in vivo, we hypothesized that applying force to the suspension culture–derived chondrocyte biomass would improve its cartilage-like characteristics and provide a new model for engineering cartilage tissue analogs. Results: In this study, we used a specialized hydrostatic pressure bioreactor system to apply mechanical forces during the growth phase to improve biochemical and biophysical properties of the biomaterial formed. We demonstrated that using this high-density suspension culture, a biomaterial more consistent with the hyaline cartilage phenotype was produced without any foreign material added. Unpassaged chondrocytes responded to a physiologically relevant hydrostatic load by significantly increasing gene expression of critical cartilage molecule collagen and aggrecan along with other cartilage relevant genes, CD44, perlecan, decorin, COMP, and iNOS. Conclusions: This study describes a self-aggregating bioreactor model without foreign material or scaffold in which chondrocytes form a cartilage tissue analog with many features similar to native cartilage. This study represents a promising scaffold-less, methodological advancement in cartilage tissue engineering with potential translational applications to cartilage repair.
Monocytes from HTLV-1–infected patients are unable to fully mature into dendritic cells
Authors: Nascimento Clarissa Rodrigues , Lima Marco Antonio , de Andrada Serpa Maria José , Espindola Otávio , Leite Ana Claudia Celestino , Echevarria-Lima Juliana 
Published: October 2010

AbstractHuman T-cell lymphotropic virus type 1 (HTLV-1) is a causative agent of adult T-cell leukemia and HTLV-1–associated myelopathy/tropical spastic paraparesis. HTLV-1–associated myelopathy/tropical spastic paraparesis is a chronic inflammatory disease characterized by loss of motor movement in response to spinal marrow cell destruction by T lymphocytes. To perform their cellular function, T cells need to be activated by antigen-presenting cells, such as dendritic cells (DCs). The aim of this work was to analyze DC differentiation and activation from monocytes of HTLV-1–infected individuals. We demonstrated that monocytes from HTLV-1–infected patients who had been stimulated to differentiate had an impaired loss of CD14 expression, expressed low levels of CD1a, and maintained secretion of tumor necrosis factor-α compared with monocytes from noninfected donors. We further evaluated DC activation by tumor necrosis factor-α. We observed that in response to activation, DCs that were derived from noninfected donors had an increase in the percentage of CD83+, CD86+, and human leukocyte antigen-DR+ cells, whereas in DCs derived from HTLV-1–infected patients, the percentage of CD83+, CD86+, and human leukocyte antigen-DR+ cells remained similar to that of nonactivated cells. Moreover, these cells had an impaired capacity to stimulate allogeneic T lymphocytes. We demonstrated that DC maturation was altered in HTLV-1–infected patients, which could contribute to the development of HTLV-1–associated diseases.
Combinatorial and distinct roles of α5 and α4 integrins in stress erythropoiesis in mice
Authors: Ulyanova Tatiana , Jiang Yi , Padilla Steven , Nakamoto Betty , Papayannopoulou Thalia 
Published: October 2010

Abstract
To delineate the role of specific members of β1 integrins in stress erythropoiesis in the adult, we compared the response to phenylhydrazine stress in 3 genetically deficient models. The survival of β1-conditionally deficient mice after phenylhydrazine is severely compromised because of their inability to mount a successful life saving splenic erythroid response, a phenotype reproduced in β1Δ/Δ reconstituted animals. The response of bone marrow to phenylhydrazine-induced stress was, unlike that of spleen, appropriate in terms of progenitor cell expansion and mobilization to peripheral blood although late differentiation defects qualitatively similar to those in spleen were present in bone marrow. In contrast to β1-deficient mice, α4Δ/Δ mice showed only a kinetic delay in recovery and similar to β1Δ/Δ, terminal maturation defects in both bone marrow and spleen, which were not present in VCAM-1Δ/Δ mice. Convergence of information from these comparative studies lends new insight to the distinct in vivo roles of α4 and α5 integrins in erythroid stress, suggesting that the presence of mainly α5β1 integrin in all hematopoietic progenitor cells interacting with splenic microenvironmental ligands/cells is instrumental for their survival and accumulation during hemolytic stress, whereas presence of α4, or of both α5 and α4, is important for completion of terminal maturation steps.
Bortezomib suppresses function and survival of plasmacytoid dendritic cells by targeting intracellular trafficking of Toll-like receptors and endoplasmic reticulum homeostasis
Authors: Hirai Makiko , Kadowaki Norimitsu , Kitawaki Toshio , Fujita Haruyuki , Takaori-Kondo Akifumi , Fukui Ryutaro , Miyake Kensuke , Maeda Takahiro , Kamihira Shimeru , Miyachi Yoshiki , Uchiyama Takashi 
Published: October 2010

AbstractDendritic cells (DCs) play a pivotal role in the pathogenesis of inflammatory disorders, so suppressing the activity of DCs is instrumental in treating such diseases. In the present study, we show that a proteasome inhibitor, bortezomib, suppresses the survival and immunostimulatory function of human plasmacytoid DCs (pDCs) by targeting 2 critical points, intracellular trafficking of nucleic acid-sensingToll-like receptors (TLRs) and endoplasmic reticulum (ER) homeostasis. Among the immune cells in blood, pDCs were the most susceptible to the killing effect of bortezomib. This correlates with a decrease in the spliced form of a transcription factor XBP1, which rescues cells from apoptosis by maintaining ER homeostasis. Bortezomib suppressed the production of interferon-α and interleukin-6 by pDCs activated with a TLR9-stimulating CpG DNA and a TLR7-stimulating influenza virus, which appears to be partially independent of apoptosis. Bortezomib inhibited translocation of TLR9 from the ER to endolysosomes but not of an ER membrane protein, Unc93B1, that delivers TLR9 to endolysosomes. Thus, bortezomib suppresses the activity of pDCs by inhibiting intracellular trafficking of TLRs through disrupting the coordinated translocation of TLRs and Unc93B1 and by disturbing ER homeostasis. This study suggests that proteasome inhibitors may alleviate inflammatory disorders such as lupus and psoriasis that involve pDCs.
Transferrin is a major determinant of hepcidin expression in hypotransferrinemic mice
Authors: Bartnikas Thomas B. , Andrews Nancy C. , Fleming Mark D. 
Published: October 2010

AbstractAs a central regulator of iron metabolism, hepcidin inhibits dietary iron absorption and macrophage iron recycling. Its expression is regulated by multiple factors including iron availability and erythropoietic activity. To investigate the role of transferrin (Tf) in the regulation of hepcidin expression by these factors in vivo, we employed the hypotransferrinemic (hpx) mouse. These Tf-deficient mice have severe microcytic anemia, tissue iron overload, and hepcidin deficiency. To determine the relationship of Tf levels and erythropoiesis to hepcidin expression, we subjected hpx mutant and control mice to a number of experimental manipulations. Treatment of hpx mice with Tf injections corrected their anemia and restored hepcidin expression. To investigate the effect of erythropoiesis on hepcidin expression, we suppressed erythropoiesis with blood transfusions or myeloablation with chemotherapeutic drugs. Transfusion of hpx animals with wild-type red blood cells led to increased hepcidin expression, while hepcidin expression in myeloablated hpx mice increased only if Tf was administered postablation. These results suggest that hepcidin expression in hpx mice is regulated both by Tf-restricted erythropoiesis and by Tf through a mechanism independent of its role in erythropoiesis.
Ndfip1-deficient mice have impaired DMT1 regulation and iron homeostasis
Authors: Foot Natalie J. , Leong Yew Ann , Dorstyn Loretta E. , Dalton Hazel E. , Ho Kristen , Zhao Lin , Garrick Michael D. , Yang Baoli , Hiwase Devendra , Kumar Sharad 
Published: October 2010

Abstract
The divalent metal ion transporter DMT1 is critical for nonheme iron import. We have previously shown that DMT1 is regulated in vitro by ubiquitination that is facilitated by the adaptor proteins Ndfip1 and Ndfip2. Here we report that in Ndfip1−/− mice fed a low- iron diet, DMT1 expression and activity in duodenal enterocytes are significant higher than in the wild-type animals. This correlates with an increase in serum iron levels and transferrin saturation. Liver and spleen iron stores were also increased in Ndfip1−/− mice fed a normal diet. Counterintuitive to the increase in iron uptake, Ndfip1−/− mice fed a low iron diet develop severe microcytic, hypochromic anemia. We demonstrate that this is due to a combination of iron deficiency and inflammatory disease in Ndfip1−/− mice, because Ndfip1−/−/Rag1−/− immunodeficient mice fed a low iron diet did not develop anemia and showed an iron overload phenotype. These data demonstrate that Ndfip1 is a critical mediator of DMT1 regulation in vivo, particularly under iron restricted conditions.
Functional blockade of α5β1 integrin induces scattering and genomic landscape remodeling of hepatic progenitor cells
Authors: Vellón Luciano , Royo Félix , Matthiesen Rune , Torres-Fuenzalida José , Lorenti Alicia , Parada Luis A 
Published: October 2010

Abstract

Background
Cell scattering is a physiological process executed by stem and progenitor cells during embryonic liver development and postnatal organ regeneration. Here, we investigated the genomic events occurring during this process induced by functional blockade of α5β1 integrin in liver progenitor cells.

Results
Cells treated with a specific antibody against α5β1 integrin exhibited cell spreading and scattering, over-expression of liver stem/progenitor cell markers and activation of the ERK1/2 and p38 MAPKs signaling cascades, in a similar manner to the process triggered by HGF/SF1 stimulation. Gene expression profiling revealed marked transcriptional changes of genes involved in cell adhesion and migration, as well as genes encoding chromatin remodeling factors. These responses were accompanied by conspicuous spatial reorganization of centromeres, while integrin genes conserved their spatial positioning in the interphase nucleus.

Conclusion
Collectively, our results demonstrate that α5β1 integrin functional blockade induces cell migration of hepatic progenitor cells, and that this involves a dramatic remodeling of the nuclear landscape.
Modifiers of notch transcriptional activity identified by genome-wide RNAi
Authors: Mourikis Philippos , Lake Robert J , Firnhaber Christopher B , DeDecker Brian S 
Published: October 2010

Abstract

Background
The Notch signaling pathway regulates a diverse array of developmental processes, and aberrant Notch signaling can lead to diseases, including cancer. To obtain a more comprehensive understanding of the genetic network that integrates into Notch signaling, we performed a genome-wide RNAi screen in Drosophila cell culture to identify genes that modify Notch-dependent transcription.

Results
Employing complementary data analyses, we found 399 putative modifiers: 189 promoting and 210 antagonizing Notch activated transcription. These modifiers included several known Notch interactors, validating the robustness of the assay. Many novel modifiers were also identified, covering a range of cellular localizations from the extracellular matrix to the nucleus, as well as a large number of proteins with unknown function. Chromatin-modifying proteins represent a major class of genes identified, including histone deacetylase and demethylase complex components and other chromatin modifying, remodeling and replacement factors. A protein-protein interaction map of the Notch-dependent transcription modifiers revealed that a large number of the identified proteins interact physically with these core chromatin components.

Conclusions
The genome-wide RNAi screen identified many genes that can modulate Notch transcriptional output. A protein interaction map of the identified genes highlighted a network of chromatin-modifying enzymes and remodelers that regulate Notch transcription. Our results open new avenues to explore the mechanisms of Notch signal regulation and the integration of this pathway into diverse cellular processes.