240 research outputs found

    Correlation Between Phase Competition and the Nucleation of a Griffiths Phase in (La1-yPry)0.7Ca0.3Mn16/18O3

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    Detailed analyses of the temperature-dependent zero field ac susceptibility of prototypical phase-separated (La1-yPry)0.7Ca0.3Mn16/18O3, 0 < y < 1, reveal features consistent with the presence of a Griffiths phase (GP), viz., an inverse susceptibility characterized by power law with 0.05 < lamda < 0.33 as y decreases towards yc < 0.85. Beyond yc = 0.85, the GP is suppressed. These data, combined with previous neutron diffraction measurements, enable a phase diagram summarizing the evolution of the GP with composition to be constructed for this system; in particular, it shows that the disorder relevant for the establishment of such a phase is linked closely to the relative volume fractions of the phase separated antiferromagnetic and ferromagnetic components, even when the recently estimated double exchange (DE) linked percolation threshold is exceeded. The influence of electron-phonon coupling can also be seen through oxygen isotope effects.Comment: 4 page

    Morphology of the medial collateral ligament of the knee

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    <p>Abstract</p> <p>Background</p> <p>Quantitative knowledge on the anatomy of the medial collateral ligament (MCL) is important for treatment of MCL injury and for MCL release during total knee arthroplasty (TKA). The objective of this study was to quantitatively determine the morphology of the MCL of human knees.</p> <p>Methods</p> <p>10 cadaveric human knees were dissected to investigate the MCL anatomy. The specimens were fixed in full extension and this position was maintained during the dissection and morphometric measurements. The outlines of the insertion sites of the superficial MCL (sMCL) and deep MCL (dMCL) were digitized using a 3D digitizing system.</p> <p>Results</p> <p>The insertion areas of the superficial MCL (sMCL) were 348.6 ± 42.8 mm<sup>2 </sup>and 79.7 ± 17.6 mm<sup>2 </sup>on the tibia and femur, respectively. The insertion areas of the deep MCL (dMCL) were 63.6 ± 13.4 mm<sup>2 </sup>and 71.9 ± 14.8 mm<sup>2 </sup>on the tibia and femur, respectively. The distances from the centroids of the tibial and femoral insertions of the sMCL to the tibial and femoral joint line were 62.4 ± 5.5 mm and 31.1 ± 4.6 mm, respectively. The distances from the centroids of dMCL in the tibial insertion and the femoral insertion to the tibial and femoral joint line were 6.5 ± 1.3 mm and 20.5 ± 4.2 mm, respectively. The distal portion of the dMCL (meniscotibial ligament - MTL) was approximately 1.7 times wider than the proximal portion of the dMCL (meniscofemoral ligament - MFL), whereas the MFL was approximately 3 times longer than the MTL.</p> <p>Conclusions</p> <p>The morphologic data on the MCL may provide useful information for improving treatments of MCL-related pathology and performing MCL release during TKA.</p

    An ancient adaptive episode of convergent molecular evolution confounds phylogenetic inference

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    Convergence can mislead phylogenetic inference by mimicking shared ancestry, but has been detected only rarely in molecular evolution. Here, we show that significant convergence occurred in snake and agamid lizard mitochondrial genomes. Most evidence, and most of the mitochondrial genome, supports one phylogenetic tree, but a subset of mostly amino acid-altering mitochondrial sites strongly support a radically different phylogeny. These sites are convergent, probably selected, and overwhelm the signal from other sites. This suggests that convergent molecular evolution can seriously mislead phylogenetics, even with large data sets. Radical phylogenies inconsistent with previous evidence should be treated cautiously

    SINEs, evolution and genome structure in the opossum

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    Short INterspersed Elements (SINEs) are non-autonomous retrotransposons, usually between 100 and 500 base pairs (bp) in length, which are ubiquitous components of eukaryotic genomes. Their activity, distribution, and evolution can be highly informative on genomic structure and evolutionary processes. To determine recent activity, we amplified more than one hundred SINE1 loci in a panel of 43 M. domestica individuals derived from five diverse geographic locations. The SINE1 family has expanded recently enough that many loci were polymorphic, and the SINE1 insertion-based genetic distances among populations reflected geographic distance. Genome-wide comparisons of SINE1 densities and GC content revealed that high SINE1 density is associated with high GC content in a few long and many short spans. Young SINE1s, whether fixed or polymorphic, showed an unbiased GC content preference for insertion, indicating that the GC preference accumulates over long time periods, possibly in periodic bursts. SINE1 evolution is thus broadly similar to human Alu evolution, although it has an independent origin. High GC content adjacent to SINE1s is strongly correlated with bias towards higher AT to GC substitutions and lower GC to AT substitutions. This is consistent with biased gene conversion, and also indicates that like chickens, but unlike eutherian mammals, GC content heterogeneity (isochore structure) is reinforced by substitution processes in the M. domestica genome. Nevertheless, both high and low GC content regions are apparently headed towards lower GC content equilibria, possibly due to a relative shift to lower recombination rates in the recent Monodelphis ancestral lineage. Like eutherians, metatherian (marsupial) mammals have evolved high CpG substitution rates, but this is apparently a convergence in process rather than a shared ancestral state. © 2007 Elsevier B.V. All rights reserved

    Pharmacologic Stem Cell Based Intervention as a New Approach to Osteoporosis Treatment in Rodents

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    Background: Osteoporosis is the most prevalent skeletal disorder, characterized by a low bone mineral density (BMD) and bone structural deterioration, leading to bone fragility fractures. Accelerated bone resorption by osteoclasts has been established as a principal mechanism in osteoporosis. However, recent experimental evidences suggest that inappropriate apoptosis of osteoblasts/osteocytes accounts for, at least in part, the imbalance in bone remodeling as occurs in osteoporosis. The aim of this study is to examine whether aspirin, which has been reported as an effective drug improving bone mineral density in human epidemiology studies, regulates the balance between bone resorption and bone formation at stem cell levels. Methods and Findings: We found that T cell-mediated bone marrow mesenchymal stem cell (BMMSC) impairment plays a crucial role in ovariectomized-induced osteoporosis. Ex vivo mechanistic studied revealed that T cell-mediated BMMSC impairment was mainly attributed to the apoptosis of BMMSCs via the Fas/Fas ligand pathway. To explore potential of using pharmacologic stem cell based intervention as an approach for osteoporosis treatment, we selected ovariectomy (OVX)-induced osteoporosis mouse model to examine feasibility and mechanism of aspirin-mediated therapy for osteoporosis. We found that aspirin can inhibit T cell activation and Fas ligand induced BMMSC apoptosis in vitro. Further, we revealed that aspirin increases osteogenesis of BMMSCs by aiming at telomerase activity and inhibits osteoclast activity in OVX mice, leading to ameliorating bone density. Conclusion: Our findings have revealed a novel osteoporosis mechanism in which activated T cells induce BMMSC apoptosis via Fas/Fas ligand pathway and suggested that pharmacologic stem cell based intervention by aspirin may be a new alternative in osteoporosis treatment including activated osteoblasts and inhibited osteoclasts. © 2008 Yamaza et al

    Content validation of the progressive collapsing foot deformity classification

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    Objective: The aim of this study was to validate the content accuracy of the PCFD classification. Methods: A survey-based study distributed through international foot and ankle programs among surgeons with vast experience in practice to analyze the terminology and interpretations used in the PCFD classification. A returned survey with completion of all questions filled out was considered a valid record. Descriptive statistical analysis was applied using SAS version 9.4 for data processing, statistical analysis, and visualization. Results: Eighty-two valid returned surveys from surgeons in 22 countries with a mean of 16 years in clinical practice were included. Among them, 80.5% of the participants considered the PCFD classification helpful in guiding decision-making, 79.3% thought it helped facilitate diagnosis and documentation, 58.5% found it easy to use, 30.5% were unlikely to use the classification, and 29.3% noted that the interpretation of the classification was not clear. Regarding the accuracy, clarity, and clinical relevance of terminology, 42.7% had difficulty in using increased foot and ankle offset, 35.4% had difficulty in using increased hindfoot moment arm, 19.5% found peritalar subluxation not clear, 13.4% found the term sinus tarsi impingement an unclear description, and 8.5% found forefoot varus difficult to diagnose. Conclusions: This international survey-based study provides readers with insights into the content of the PCFD classification. The findings indicate that some terminologies used in the PCFD classification are not universally understood. The authors recommend that modifications may be beneficial to enhance the accuracy and user-friendliness of the PCFD classification. Level of Evidence II; Retrospective study

    Phosphoric Metabolites Link Phosphate Import and Polysaccharide Biosynthesis for Candida albicans Cell Wall Maintenance

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    ACKNOWLEDGMENTS We declare no conflicts of interest. We thank JesĂșs Pla for his kind gift of the anti-Mkc1 antibody and Kristin Moffitt and Richard Malley for generous advice in ELISA technology and use of the ELISA reader. We thank Tahmeena Chowdhury for scientific discussions leading up to this work. We thank the Candida Genome Database. N.-N.L., M.A.-Z., W.Q., and J.R.K. were supported by R21 AI137716 and by Boston Children’s Hospital Department of Pediatrics. M.A.-Z. was partially funded by the Alfonso Martin Escudero Foundation. J.D.-A. and O.L. were funded by the Boston Children’s Hospital Department of Pediatrics and U19 AI118608-01A1. N.A.R.G. was supported by the Wellcome Trust and the Medical Research Council Centre for Medical Mycology (MR/N006364/1).Peer reviewedPublisher PD

    Transforming Growth Factor-ÎČ Production and Myeloid Cells Are an Effector Mechanism through Which CD1d-restricted T Cells Block Cytotoxic T Lymphocyte–mediated Tumor Immunosurveillance: Abrogation Prevents Tumor Recurrence

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    Our previous work demonstrated that cytotoxic T lymphocyte (CTL)-mediated tumor immunosurveillance of the 15-12RM tumor could be suppressed by a CD1d-restricted lymphocyte, most likely a natural killer (NK) T cell, which produces interleukin (IL)-13. Here we present evidence for the effector elements in this suppressive pathway. T cell–reconstituted recombination activating gene (RAG)2 knockout (KO) and RAG2/IL-4 receptor α double KO mice showed that inhibition of immunosurveillance requires IL-13 responsiveness by a non–T non–B cell. Such nonlymphoid splenocytes from tumor-bearing mice produced more transforming growth factor (TGF)-ÎČ, a potent inhibitor of CTL, ex vivo than such cells from naive mice, and this TGF-ÎČ production was dependent on the presence in vivo of both IL-13 and CD1d-restricted T cells. Ex vivo TGF-ÎČ production was also abrogated by depleting either CD11b+ or Gr-1+ cells from the nonlymphoid cells of tumor-bearing mice. Further, blocking TGF-ÎČ or depleting Gr-1+ cells in vivo prevented the tumor recurrence, implying that TGF-ÎČ made by a CD11b+ Gr-1+ myeloid cell, in an IL-13 and CD1d-restricted T cell–dependent mechanism, is necessary for down-regulation of tumor immunosurveillance. Identification of this stepwise regulation of immunosurveillance, involving CD1-restricted T cells, IL-13, myeloid cells, and TGF-ÎČ, explains previous observations on myeloid suppressor cells or TGF-ÎČ and provides insights for targeted approaches for cancer immunotherapy, including synergistic blockade of TGF-ÎČ and IL-13
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