bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cav1.1 controls frequency-dependent events regulating adult skeletal muscle plasticity
Authors: Jorquera Gonzalo , Altamirano Francisco , Contreras-Ferrat Ariel , Almarza Gonzalo , Buvinic Sonja , Jacquemond Vincent , Jaimovich Enrique , Casas Mariana 
Published: January 2013

Summary
An important pending question in neuromuscular biology is how skeletal muscle cells decipher the stimulation pattern coming from motoneurons to define their phenotype as slow or fast twitch muscle fibers. We have previously shown that voltage-gated L-type calcium channel (Cav1.1) acts as a voltage sensor for activation of inositol (1,4,5)-trisphosphate [Ins(1,4,5)P3]-dependent Ca2+ signals that regulates gene expression. ATP released by muscle cells after electrical stimulation through pannexin-1 channels plays a key role in this process. We show now that stimulation frequency determines both ATP release and Ins(1,4,5)P3 production in adult skeletal muscle and that Cav1.1 and pannexin-1 colocalize in the transverse tubules. Both ATP release and increased Ins(1,4,5)P3 was seen in flexor digitorum brevis fibers stimulated with 270 pulses at 20 Hz, but not at 90 Hz. 20 Hz stimulation induced transcriptional changes related to fast-to-slow muscle fiber phenotype transition that required ATP release. Addition of 30 µM ATP to fibers induced the same transcriptional changes observed after 20 Hz stimulation. Myotubes lacking the Cav1.1-α1 subunit released almost no ATP after electrical stimulation, showing that Cav1.1 has a central role in this process. In adult muscle fibers, ATP release and the transcriptional changes produced by 20 Hz stimulation were blocked by both the Cav1.1 antagonist nifedipine (25 µM) and by the Cav1.1 agonist (-)S-BayK 8644 (10 µM). We propose a new role for Cav1.1, independent of its calcium channel activity, in the activation of signaling pathways allowing muscle fibers to decipher the frequency of electrical stimulation and to activate specific transcriptional programs that define their phenotype.
Constitutive Cdk2 activity promotes aneuploidy while altering the spindle assembly and tetraploidy checkpoints
Authors: Jahn Stephan C. , Corsino Patrick E. , Davis Bradley J. , Law Mary E. , Nørgaard Peter , Law Brian K. 
Published: January 2013

Summary
The cell has many mechanisms for protecting the integrity of its genome. These mechanisms are often weakened or absent in many cancers, leading to high rates of chromosomal instability in tumors. Control of the cell cycle is crucial for the function of these checkpoints, and is frequently lost in cancers as well. Overexpression of Cyclin D1 in a large number of breast cancers causes overactivation of the cyclin-dependent kinases, including Cdk2. Constitutive Cdk2 activation through Cyclin D1 generates tumors in mice that are aneuploid and have many characteristics indicative of chromosomal instability. Expression of these complexes in the MCF10A cell line leads to retinoblastoma protein (Rb) hyperphosphorylation, a subsequent increase in proliferation rate, and increased expression of the spindle assembly checkpoint protein Mad2. This results in a strengthening of the spindle assembly checkpoint and renders cells more sensitive to the spindle poison paclitaxel. Constitutive Rb phosphorylation also causes a weakening of the p53-dependent tetraploidy checkpoint. Cells with overactive Cdk2 fail to arrest after mitotic slippage in the presence of paclitaxel or cytokinesis failure during treatment with cytochalasin-B, generating 8N populations. This additional increase in DNA content appears to further intensify the tetraploidy checkpoint in a step-wise manner. These polyploid cells are not viable long-term, either failing to undergo division or creating daughter cells that are unable to undergo subsequent division. This study raises intriguing questions about the treatment of tumors with overactive Cdk2.
Spatial accuracy of a rapid defense behavior in caterpillars
Authors: van Griethuijsen Linnea I. , Banks Kelly M. , Trimmer Barry A. 
Published: January 2013

SUMMARYAimed movements require that an animal accurately locates the target and correctly reaches that location. One such behavior is the defensive strike seen in Manduca sexta larva. These caterpillars respond to noxious mechanical stimuli applied to their abdomen with a strike of the mandibles towards the location of the stimulus. The accuracy with which the first strike movement reaches the stimulus site depends on the location of the stimulus. Reponses to dorsal stimuli are less accurate than those to ventral stimuli and the mandibles generally land ventral to the stimulus site. Responses to stimuli applied to anterior abdominal segments are less accurate than responses to stimuli applied to more posterior segments and the mandibles generally land posterior to the stimulus site. A trade-off between duration of the strike and radial accuracy is only seen in the anterior stimulus location (body segment A4). The lower accuracy of the responses to anterior and dorsal stimuli can be explained by the morphology of the animal; to reach these areas the caterpillar needs to move its body into a tight curve. Nevertheless, the accuracy is not exact in locations that the animal has shown it can reach, which suggests that consistently aiming more ventral and posterior of the stimulation site might be a defense strategy.
Mice selectively bred for high voluntary wheel running have larger midbrains: support for the mosaic model of brain evolution
Authors: Kolb E. M. , Rezende E. L. , Holness L. , Radtke A. , Lee S. K. , Obenaus A. , Garland T. 
Published: January 2013

SUMMARYIncreased brain size, relative to body mass, is a primary characteristic distinguishing the mammalian lineage. This greater encephalization has come with increased behavioral complexity and, accordingly, it has been suggested that selection on behavioral traits has been a significant factor leading to the evolution of larger whole-brain mass. In addition, brains may evolve in a mosaic fashion, with functional components having some freedom to evolve independently from other components, irrespective of, or in addition to, changes in size of the whole brain. We tested whether long-term selective breeding for high voluntary wheel running in laboratory house mice results in changes in brain size, and whether those changes have occurred in a concerted or mosaic fashion. We measured wet and dry brain mass via dissections and brain volume with ex vivo magnetic resonance imaging of brains that distinguished the caudate-putamen, hippocampus, midbrain, cerebellum and forebrain. Adjusting for body mass as a covariate, mice from the four replicate high-runner (HR) lines had statistically larger non-cerebellar wet and dry brain masses than those from four non-selected control lines, with no differences in cerebellum wet or dry mass or volume. Moreover, the midbrain volume in HR mice was ~13% larger (P&lt;0.05), while volumes of the caudate-putamen, hippocampus, cerebellum and forebrain did not differ statistically between HR and control lines. We hypothesize that the enlarged midbrain of HR mice is related to altered neurophysiological function in their dopaminergic system. To our knowledge, this is the first example in which selection for a particular mammalian behavior has been shown to result in a change in size of a specific brain region.
Reconsideration of the Optically Investigated Competitive Reaction between Cytochrome c Reduction due to Superoxide and Superoxide Dismutation in the Presence of Xanthine Oxidase
Authors: Mitsuta Keiichi 
Published: January 2013

Abstract
Though reported in 1973 by Sawada and Yamazaki, the experimental data obtained from kinetic competition between cytochrome c reduction due to superoxide and spontaneous dismutation of superoxide have long been disregarded because of disagreement with the experimental values obtained from pulse radiolysis. Assuming that the cause of this disagreement could be explained as being an acceleration of the dismutation rate due to the superoxide dismutase (SOD)-like activity possessed by xanthine oxidase (XOD), the value of the rate constant, kXOD, for the reaction between XOD and superoxide that was considered necessary to explain their experimental findings was calculated. As a result, the values of kXOD have been found to be 3.0 × 106 (pH 5), 4.4 × 106 (pH 5.5), 5.5 × 106 (pH 7), 3.6 × 106 (pH 7.8), and 9.2 × 105 (pH 8.5) in M−1 s−1. These values are good matches for two previous experimental values, 2.1 × 106 (pH 7.8) and 8.0 × 105 (pH 12) in M−1 s−1, obtained from the present author’s ESR spin-trapping experiments, and are considered to show the overall image of the SOD-like function acquired by XOD in the long course of its molecular evolution.
Evaluation of a Self-Administered Oral Glucose Tolerance Test
Authors: Bethel M. Angelyn , Price Hermione C. , Sourij Harald , White Sarah , Coleman Ruth L. , Ring Arne , Kennedy Irene E.C. , Tucker Lynne , Holman Rury R. 
Published: January 2013

OBJECTIVE
To assess the feasibility of using a disposable, self-administered, capillary blood sampling oral glucose tolerance test (OGTT) device in a community setting.

RESEARCH DESIGN AND METHODS
Eighteen healthy and 12 type 2 diabetic volunteers underwent six 75-g OGTTs using a prototype device in the following three settings: unaided at home (twice); unaided but observed in clinic (twice); and performed by a nurse with simultaneous laboratory glucose assays of 0- and 120-min venous plasma samples (twice). The device displayed no results. A detachable data recorder returned to the clinic provided plasma-equivalent 0- and 120-min glucose values and key parameters, including test date, start and end times, and time taken to consume the glucose drink.

RESULTS
The device was universally popular with participants and was perceived as easy to use, and the ability to test at home was well liked. Device failures meant that 0- and 120-min glucose values were obtained for only 141 (78%) of the 180 OGTTs performed, independent of setting. Device glucose measurements showed a mean bias compared with laboratory-measured values of +0.9 at 5.0 mmol/L increasing to +4.4 at 15.0 mmol/L. Paired device glucose values were equally reproducible across settings, with repeat testing showing no training effect regardless of setting order.

CONCLUSIONS
Self-administered OGTTs can be performed successfully by untrained individuals in a community setting. With improved device reliability and appropriate calibration, this novel technology could be used in routine practice to screen people who might need a formal OGTT to confirm the presence of impaired glucose tolerance or diabetes.
Feeding and Healing the World: Through Regenerative Agriculture and Permaculture
Authors: Rhodes Christopher J. 
Published: January 2013

The study of soil is a mature science, whereas related practical methods of regenerative agriculture and permaculture are not. However, despite a paucity of detailed peer reviewed research published on these topics, there is overwhelming evidence both that the methods work and they may offer the means to address a number of prevailing environmental challenges, e.g. peak oil, climate change, carbon capture, unsustainable agriculture and food shortages, peak phosphorus (phosphate), water shortages, environmental pollution, desert reclamation, and soil degradation. What is lacking is a proper scientific study, made in hand with actual development projects. By elucidating the scientific basis of these remarkable phenomena, we may obtain the means for solving some of the otherwise insurmountable problems confronting humanity, simply by observing, and working with, the patterns and forces of nature. This article is intended as a call to arms to make serious investment in researching and actualising these methods on a global scale. Despite claims that peak oil is no longer a threat because vast resources of gas and shale oil (tight oil) can now be recovered by fracking (hydraulic fracturing) combined with horizontal drilling, the reality is that proven actual reserves are only adequate to delay the peak by a few years. Furthermore, because of the rapid depletion rates of flow from gas wells and oil wells that are accessed by fracking, it will be necessary to drill continuously and relentlessly to maintain output, and there are material limits of equipment, technology and trained personnel to do this. Moreover, to make any sensible difference to the liquid fuel crisis, which is the most immediate consequence of peak oil, it would be necessary to convert the world's one billion vehicles to run on natural gas rather than liquid fuels refined from crude oil, and this would take some considerable time and effort. The loss of widespread personalised transportation is thus inevitable and imminent, meaning a loss of globalised civilisation and a mandatory return to living in smaller localised communities. Permaculture and regenerative agriculture offer potentially the means to provide food and materials on the small scale, and address the wider issues of carbon emissions, and resource shortages. Since over half the World's population lives in cities, it seems likely that strengthening the resilience of these environments, using urban permaculture, may be a crucial strategy in achieving a measured descent in our use of energy and other resources, rather than an abrupt collapse of civilization.
Identification of Immunogenic HLA-B*27:05 Binding Peptides of Salmonella Outer Membrane Protein in Patients with Reactive Arthritis and Undifferentiated Spondyloarthropathy
Authors: SINGH AMIT KUMAR , AGGARWAL AMITA , CHAURASIA SMRITI , MISRA RAMNATH 
Published: January 2013

Objective.Salmonella outer membrane proteins (OMP) are major immunogenic targets to synovial fluid lymphocytes of patients with reactive arthritis (ReA)/undifferentiated spondyloarthropathy (uSpA). Because these patients have genetic predisposition to HLA-B*27 and its subtype HLA-B*27:05, we sought to identify immunogenic HLA-B*27:05-binding salmonella OMP peptides in patients with ReA/uSpA.Methods.A total of 125 HLA-B*27:05-binding salmonella OMP peptides identified using ProPred-I software were synthesized and grouped in 23 pools. The peptide pools, along with crude enteric bacterial lysates and salmonella OMP, were cultured with synovial fluid (SF) or peripheral blood mononuclear cells (PBMC) from 23 patients with ReA/uSpA, 10 with rheumatoid arthritis (RA), and 10 healthy individuals in 96-well culture plates. Proliferation was measured by tritiated thymidine uptake and interferon-γ (IFN-γ) levels in culture supernatant. Individual peptides from pools having significant responses were retested with cryopreserved cells. Immunogenic peptides thus identified were further tested in 5 additional new patients with ReA/uSpA by flow cytometry. A Basic Local Alignment Search Tool program was used to search for similar peptides from a protein bank of arthritogenic bacteria and human protein.Results.Nineteen of 23 SFMC from ReA/uSpA showed a significant proliferative response to salmonella OMP, with minimal response of PBMC (1/10) from ReA/uSpA, SFMC from RA (1/10), or PBMC from controls (1/10). Nine salmonella OMP peptides, QRAEMLPTL, SRSGLNIAL, LRFLYAKSL, RLEGTWVKL, ARCIAPYAL, KLFLTTAAL, YRNSDFFGL, QRPAVRVKL, and YRVGPGDVL, were identified. Response to QRAEMLPTL was seen in 6/7 HLA-B*27:05-positive patients. All immunogenic peptides had sequence similarity with peptides from arthritogenic bacterial proteins, while 5 had similarity with peptides from human proteins.ConclusionNine novel immunogenic OMP peptides binding to HLA-B*27:05 were identified that showed sequence similarity with other arthritogenic bacteria.
Comparative Effectiveness of Nonbiologic versus Biologic Disease-modifying Antirheumatic Drugs for Rheumatoid Arthritis
Authors: DEWITT ESI MORGAN , LI YANHONG , CURTIS JEFFREY R. , GLICK HENRY A. , GREENBERG JEFFREY D. , ANSTROM KEVIN J. , KREMER JOEL M. , REED GEORGE , SCHULMAN KEVIN A. , REED SHELBY D. 
Published: January 2013

Objective.To evaluate the comparative effectiveness of nonbiologic disease-modifying antirheumatic drugs (DMARD) versus biologic DMARD (bDMARD) for treatment of rheumatoid arthritis (RA), using 2 common analytic approaches.Methods.We analyzed change in Clinical Disease Activity Index (CDAI) scores in patients with RA enrolled in a US-based observational registry from 2001 to 2008 using multivariable (MV) regression and propensity score (PS) matching. Among patients who initiated treatment with a nonbiologic DMARD (n = 1729), we compared patients who switched to, or added, another nonbiologic (n = 182) or a bDMARD (n = 342) at 5, 9, and 24 months after treatment change.Results.Both analytic approaches showed that patients switching to or adding another nonbiologic DMARD demonstrated improvement across 9 and 24 months (both p < 0.001). Both approaches also demonstrated greater improvement in CDAI among recipients of bDMARD relative to a second nonbiologic DMARD at 5 months (p < 0.02). The MV regression approach upheld these results at 9 and 24 months (p < 0.03). In contrast, the PS-matching approach did not show a sustained advantage with bDMARD at these later timepoints, possibly because of lower statistical power and/or lower baseline disease activity in the PS-matched cohort.Conclusion.Patients in both treatment groups generally experienced lower CDAI scores across time. Patients switching to bDMARD demonstrated greater improvement than patients switching to nonbiologic DMARD with both analytic approaches at 5 months. Relative advantages with bDMARD were observed at 9 and 24 months only with MV regression. These analyses provide a practical example of how findings in comparative effectiveness research can diverge with different methodological approaches.
BAFF Expression Correlates with Idiopathic Inflammatory Myopathy Disease Activity Measures and Autoantibodies
Authors: LÓPEZ De PADILLA CONSUELO M. , McNALLAN KELLY T. , CROWSON CYNTHIA S. , BILGIC HATICE , BRAM RICHARD J. , HEIN MOLLY S. , YTTERBERG STEVEN R. , AMIN SHREYASEE , PETERSON ERIK J. , BAECHLER EMILY C. , REED ANN M. 
Published: January 2013

Objective.To investigate B cell survival cytokine messenger RNA (mRNA) levels as biomarkers of idiopathic inflammatory myopathies (IIM).Methods.We measured and compared mRNA levels of B cell survival cytokines by quantitative real-time polymerase chain reaction in 98 patients with IIM, 38 patients with systemic lupus erythematosus, and 21 healthy controls. The cytokines were B cell-activating factor belonging to the tumor necrosis factor family (BAFF); ΔBAFF; and a proliferation-inducing ligand (APRIL); and their receptors BAFF-R, transmembrane activator and calcium modulator and cyclophilin ligand interactor, and B cell maturation antigen (BCMA). We also identified autoantibodies, including anti-Sm, anti-RNP, anti-SSA/Ro, anti-SSB/La, anti-topoisomerase 1, anti-hystidyl-tRNA synthetase, anti-ribosomal P, and anti-chromatin. Clinical disease activity was assessed by the International Myositis Assessment and Clinical Studies core set tool. We examined correlation of mRNA with disease activity, medication use, and autoantibodies.Results.We found a positive correlation of BAFF and ΔBAFF expression with 3 disease activity measures, with ΔBAFF having a stronger correlation. Similarly, anti-SSA/Ro-52 and/or anti-SSA/Ro-60 had a strong positive correlation with mRNA levels of BAFF and ΔBAFF, and with relative ratios of BAFF/APRIL and BCMA/BAFF-R.Conclusion.These findings highlight the potential importance of BAFF, ΔBAFF, and BAFF-R in the pathogenesis of IIM, and suggest an important role in the assessment of disease activity.
A New Approach to Prevention of Knee Osteoarthritis: Reducing Medial Load in the Contralateral Knee
Authors: JONES RICHARD K. , CHAPMAN GRAHAM J. , FINDLOW ANDREW H. , FORSYTHE LAURA , PARKES MATTHEW J. , SULTAN JAWAD , FELSON DAVID T. 
Published: January 2013

Objective.Few if any prevention strategies are available for knee osteoarthritis (OA). In those with symptomatic medial OA, the contralateral knee may be at high risk of disease, and a reduction in medial loading in that knee might prevent disease or its progression there. Our aim was to determine how often persons with medial OA on 1 side had either concurrent or later medial OA on the contralateral side, and whether an intervention known to reduce medial loading in affected knees with medial OA might reduce medial loading in the contralateral knee. Lateral wedge insoles reduce loading across an affected medial knee but their effect on the contralateral knee is unknown.Methods.To determine the proportion of persons with medial knee OA who had concurrent medial contralateral OA or developed contralateral medial OA later, we examined knee radiographs from the longitudinal Framingham Osteoarthritis Study. Then, to examine an approach to reducing medial load in the contralateral knee, 51 people from a separate study with painful medial tibiofemoral OA underwent gait analysis wearing bilateral controlled shoes with no insoles, and then with 2 types of wedge insoles laterally posted by 5°. Primary outcome was the external knee adduction moment (EKAM) in the contralateral knee. Nonparametric CI were constructed around the median differences in percentage change in the affected and contralateral sides.Results.Of Framingham subjects with medial radiograph knee OA, 137/152 (90%) either had concurrent contralateral medial OA or developed it within 10 years. Of those with medial symptomatic knee OA, 43/67 (64%) had or developed the same disease state in the contralateral knee. Compared to a control shoe, medial loading was reduced substantially on both the affected (median percentage EKAM change −4.84%; 95% CI −11.33% to −0.65%) and contralateral sides (median percentage EKAM change −9.34%; 95% CI −10.57% to −6.45%).Conclusion.In persons with medial OA, the contralateral knee is also at high risk of medial OA. Bilateral reduction in medial loading in knees by use of strategies such as lateral wedge insoles might not only reduce medial load in affected knees but prevent knee OA or its progression on the contralateral side.
Symptoms Related to Tumor Necrosis Factor Receptor 1-associated Periodic Syndrome, Multiple Sclerosis, and Severe Rheumatoid Arthritis in Patients Carrying the TNF Receptor Superfamily 1A D12E/p.Asp41Glu Mutation
Authors: HAVLA JOACHIM , LOHSE PETER , GERDES LISA ANN , HOHLFELD REINHARD , KÜMPFEL TANIA 
Published: January 2013

Objective.Tumor necrosis factor (TNF) receptor 1–associated periodic syndrome (TRAPS) is an autoinflammatory disorder caused by autosomal dominantly inherited mutations in the TNF receptor superfamily 1A (TNFRSF1A) gene. The D12E substitution has been described only once to date, in a 4-year-old boy with fever.Methods.For DNA sequence analysis of theTNFRSF1Agene, genomic DNA was isolated, amplified by PCR, purified, and sequenced.Results.We describe 3 families (8 subjects) with the TNFRSF1A D12E substitution and TRAPS-related symptoms, in 4 cases associated with the autoimmune diseases multiple sclerosis and rheumatoid arthritis.Conclusion.The clinical phenotype might be associated with the TNFRSF1A D12E mutation. There is a close pathophysiological relationship between TNF signaling and autoimmune disorders.