bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Posterior Horn Medial Meniscus Root Tear on In Vivo Knee Kinematics
Authors: Marsh Chelsea A. , Martin Daniel E. , Harner Christopher D. , Tashman Scott
Published: July 2014

Background:

Medial meniscus root tear (MMRT) is a recently recognized yet frequently missed meniscal tear pattern that biomechanically creates an environment approaching meniscal deficiency.

Hypothesis/Purpose:

The purpose of this study was to assess the effect of MMRT on tibiofemoral kinematics and arthrokinematics during daily activities by comparing the injured knees of subjects with isolated MMRT to their uninjured contralateral knees. The hypothesis was that the injured knee will demonstrate significantly more lateral tibial translation and adduction than the uninjured knee, and that the medial compartment will exhibit significantly different arthrokinematics than the lateral compartment in the affected limb.

Study Design:

Cross-sectional study; Level of evidence, 3.

Methods:

Seven subjects with isolated MMRT were recruited and volumetric, density-based 3-dimensional models of their distal femurs and proximal tibia were created from computed tomography scans. High-speed, biplane radiographs were obtained of both their affected and unaffected knees. Moving 3-dimensional models of tibiofemoral kinematics were calculated using model-based tracking to assess overall kinematic variables and specific measures of tibiofemoral joint contact. The affected knees of the subjects were then compared to their unaffected contralateral knees.

Results:

Affected knees demonstrated significantly more lateral tibial translation than the uninjured contralateral limb in all dynamic activities. Additionally, the medial compartment displayed greater amounts of mobility than the lateral compartment in the injured limbs.

Conclusion:

This study suggests that MMRT causes significant changes in in vivo knee kinematics and arthrokinematics and that the magnitude of these changes is influenced by dynamic task difficulty.

Clinical Relevance:

Medial meniscus root tears lead to significant changes in joint arthrokinematics, with increased lateral tibial translation and greater medial compartment excursion. With complete root tears, essentially 100% of circumferential fibers are lost. This study will further our knowledge of meniscal deficiency and osteoarthritis and provide a baseline for more common forms of medial meniscal injuries (vertical, horizontal, radial), with various degrees of circumferential fiber function remaining.
Musical Meaning in the Lives of Those Affected by the Holocaust
Authors: Cunningham Deborah A.
Published: July 2014

This qualitative study investigated the role of music in the lives of those affected by the Holocaust. Participants were identified through purposeful and snowball sampling techniques, and a total of five were selected based on their connection to the Holocaust. Participants included those incarcerated in camps and ghettos, those who escaped incarceration, and a child of survivors. Each participant was interviewed using a semistructured interview schedule. Interview transcripts were transcribed and coded using coding categories generated from recurring patterns and ideas. The data were analyzed to identify emerging themes. The overarching theme is that music has a multiplicity of meanings to humans, is used in different ways at different times, and does not hold the same meaning for all people. Findings from this investigation pose questions for music educators, concerning the way music is taught in school settings.
The Long-Term Effects of Childhood Music Instruction on Intelligence and General Cognitive Abilities
Authors: Costa-Giomi Eugenia
Published: July 2014

This article reviews research on the effects of music instruction on general cognitive abilities. The review of more than 75 reports shows (1) the consistency in results pertaining to the short-term effects of music instruction on cognitive abilities and the lack of clear evidence on the long-term effects on intelligence; (2) the complex nature of the relationship between music instruction and intellectual measures due to the intervention of factors associated with who is interested, studies, perseveres, and succeeds in learning music; and (3) the importance of music practice on the long-term cognitive benefits of music instruction.
Characteristics of “Music Education” Videos Posted on YouTube
Authors: Whitaker Jennifer A. , Orman Evelyn K. , Yarbrough Cornelia
Published: July 2014

This content analysis sought to determine information related to users uploading, general content, and specific characteristics of music education videos on YouTube. A total of 1,761 videos from a keyword search of “music education” were viewed and categorized. Results for relevant videos indicated users posted videos under 698 different usernames, with postings under a single username ranging from 1 to 51. Users’ self-reported country affiliation varied across 58 different countries. The number of countries represented in this sample indicates YouTube users from around the globe are interested in sharing music education content. Results relating to the content of videos categorized as relevant to music education ( n = 1,352) revealed the most observed categories were performance (36%), followed by teaching (28%), public relations (27%), and industry (10%). Teaching videos were mostly tutorials (65%). Participants across all video categories were predominantly adults, university age, or fit multiple age categories.
Religious Music, the Public Schools, and the Establishment Clause
Authors: Cranmore Jeff , Fossey Richard
Published: July 2014

Various issues relating to education and religion continue to appear in federal court. One issue that is most relevant to music educators is the use of religious music in school music curriculum. Although no federal guidelines exist as to what is acceptable usage, a number of federal cases have addressed the various issues, from the use of religious music as a teacher tool to the performance of music in a religious setting, such as a church. This article seeks to inform readers of previous federal case decisions and provide some guidance for teachers in making music selections, based on those decisions and an analysis of current district policies.
Listening and Musical Engagement
Authors: Diaz Frank M.
Published: July 2014

Music educators often use guided listening strategies as a means of enhancing engagement during music listening activities. Although previous research suggests that these strategies are indeed helpful in facilitating some form of cognitive and emotional engagement, little is known about how these strategies might function for music of differing styles, or how they might affect attention, emotion, and peak affective experiences specifically during listening. In this study, these factors were investigated through the lens of three previously examined strategies: a distraction index, labeling of musical elements, and unguided listening. General findings suggest that the most consequential factor in enhancing musical engagement was presenting students with some type of goal either during or at the end of listening, regardless of the musical style or listening strategy used throughout the task. Furthermore, implications of the use of listening strategies during academic settings are discussed.
Phase 2 study of imexon, a prooxidant molecule, in relapsed and refractory B-cell non-Hodgkin lymphoma
Authors: Barr Paul M. , Miller Thomas P. , Friedberg Jonathan W. , Peterson Derick R. , Baran Andrea M. , Herr Megan , Spier Catherine M. , Cui Haiyan , Roe Denise J. , Persky Daniel O. , Casulo Carla , Littleton Jamie , Schwartz Mark , Puvvada Soham , Landowski Terry H. , Rimsza Lisa M. , Dorr Robert T. , Fisher Richard I. , Bernstein Steven H. , Briehl Margaret M.
Published: July 2014

Key Points

Clinical responsiveness to imexon represents the first demonstration of efficacy with modulating cellular redox in B-cell NHL. Antioxidant-related gene expression predicted for response to imexon.
Association between hospital case volume and mortality in non-elderly pneumonia patients stratified by severity: a retrospective cohort study
Authors: Kumamaru Hiraku , Tsugawa Yusuke , Horiguchi Hiromasa , Kumamaru Kanako Kunishima , Hashimoto Hideki , Yasunaga Hideo
Published: July 2014

Background

The characteristics and aetiology of pneumonia in the non-elderly population is distinct from that in the elderly population. While a few studies have reported an inverse association between hospital case volume and clinical outcome in elderly pneumonia patients, the evidence is lacking in a younger population. In addition, the relationship between volume and outcome may be different in severe pneumonia cases than in mild cases. In this context, we tested two hypotheses: 1) non-elderly pneumonia patients treated at hospitals with larger case volume have better clinical outcome compared with those treated at lower case volume hospitals; 2) the volume-outcome relationship differs by the severity of the pneumonia.

Methods

We conducted the study using the Japanese Diagnosis Procedure Combination database. Patients aged 18–64 years discharged from the participating hospitals between July to December 2010 were included. The hospitals were categorized into four groups (very-low, low, medium, high) based on volume quartiles. The association between hospital case volume and in-hospital mortality was evaluated using multivariate logistic regression with generalized estimating equations adjusting for pneumonia severity, patient demographics and comorbidity score, and hospital academic status. We further analyzed the relationship by modified A-DROP pneumonia severity score calculated using the four severity indices: dehydration, low oxygen saturation, orientation disturbance, and decreased systolic blood pressure.

Results

We identified 8,293 cases of pneumonia at 896 hospitals across Japan, with 273 in-hospital deaths (3.3%). In the overall population, no significant association between hospital volume and in-hospital mortality was observed. However, when stratified by pneumonia severity score, higher hospital volume was associated with lower in-hospital mortality at the intermediate severity level (modified A-DROP score = 2) (odds ratio (OR) of very low vs. high: 2.70; 95% confidence interval (CI): 1.12–6.55, OR of low vs. high: 2.40; 95% CI:0.99–5.83). No significant association was observed for other severity strata.

Conclusions

Hospital case volume was inversely associated with in-hospital mortality in non-elderly pneumonia patients with intermediate pneumonia severity. Our result suggests room for potential improvement in the quality of care in hospitals with lower volume, to improve treatment outcomes particularly in patients admitted with intermediate pneumonia severity.
Design of double codebook based on 3D dual-polarized channel for multiuser MIMO system
Authors: Han Yu , Jin Shi , Li Xiao , Huang Yongming , Jiang Lei , Wang Gang
Published: July 2014

This paper proposes a precoding method based on double codebook for multiuser three-dimensional multiple-input multiple-output (3D MIMO) system deployed with dual-polarized antenna array. Considering the block diagonal feature of the transmit correlation matrix of 3D dual-polarized channel, we adopt the double codebook structure, where the precoding matrix is composed of an inner long-term matrix and an outer short-term matrix. Then, we introduce a set of 3D beams which possess good discrimination in horizontal and vertical domains to be the basic beam set and adopt a topology describing the 3D beam set to illustrate the angle information in an intuitive way. For the purpose of multiuser transmission, we also propose a corresponding limited channel information feedback scheme and a user scheduling criteria based on this double codebook structure. Simulation results demonstrate that the precoding method based on double codebook for the dual-polarized 3D MIMO system effectively improves system throughput compared with 2D transmission scheme.
Intelligent fuzzy approach for fast fractal image compression
Authors: Nodehi Ali , Sulong Ghazali , Al-Rodhaan Mznah , Al-Dhelaan Abdullah , Rehman Amjad , Saba Tanzila
Published: July 2014

Fractal image compression (FIC) is recognized as a NP-hard problem, and it suffers from a high number of mean square error (MSE) computations. In this paper, a two-phase algorithm was proposed to reduce the MSE computation of FIC. In the first phase, based on edge property, range and domains are arranged. In the second one, imperialist competitive algorithm (ICA) is used according to the classified blocks. For maintaining the quality of the retrieved image and accelerating algorithm operation, we divided the solutions into two groups: developed countries and undeveloped countries. Simulations were carried out to evaluate the performance of the developed approach. Promising results thus achieved exhibit performance better than genetic algorithm (GA)-based and Full-search algorithms in terms of decreasing the number of MSE computations. The number of MSE computations was reduced by the proposed algorithm for 463 times faster compared to the Full-search algorithm, although the retrieved image quality did not have a considerable change.
MIP-3β/CCL19 is associated with the intrathecal invasion of mononuclear cells in neuroinflammatory and non-neuroinflammatory CNS diseases in dogs
Authors: Bartels Janina , Darrow Brett G , Schatzberg Scott J , Bu Lijing , Carlson Regina , Tipold Andrea
Published: July 2014

Background

Chemokines such as MIP-3β/CCL19 are important factors in the mechanism of cell migration and pathogenesis of central nervous system (CNS) inflammatory reactions. The hypothesis of this study is that CCL19, also known as MIP-3β, is involved in the pathogenesis of inflammatory and non-inflammatory CNS diseases of dogs. Experiments were performed on cerebrospinal fluid (CSF) and serum samples of dogs affected with steroid responsive meningitis-arteritis (SRMA) during the acute phase as well as during treatment. Dogs with SRMA were compared to dogs with presumed meningoencephalomyelitis of unknown origin (MUO), and both groups sub-categorized into dogs receiving no therapy and with patients receiving prednisolone therapy. Idiopathic epilepsy (IE), a group with normal CSF cell count, was used as a control. Additionally, dogs with intervertebral disc disease (IVDD) of varying severity were analyzed. Chemokine concentrations were determined by enzyme linked immunosorbent assay. Migration assays were performed on seven selected CSF samples using a disposable 96-well chemotaxis chamber.

Results

CCL19 was detectable in CSF samples of all dogs. Dogs with untreated SRMA and MUO displayed pronounced CCL19 elevations compared to the control group and patients receiving glucocorticosteroid treatment. CSF cell counts of untreated SRMA and MUO patients were significantly positively correlated with the CCL19 CSF concentration. IVDD patients also had elevated CCL19 concentration compared to controls, but values were considerably lower than in inflammatory CNS diseases. Selected CSF samples displayed chemotactic activity for mononuclear cells in the migration assay.

Conclusions

CCL19 CSF concentrations were markedly elevated in patients affected with the neuroinflammatory diseases SRMA and MUO and showed a strong correlation with the CSF cell count. This chemokine may play an important role in the pathogenesis of SRMA and MUO. The elevation of CSF CCL19 in IVDD suggests that it may also be involved in the secondary wave of spinal cord injuries.
Cleavage site and Ectodomain of HA2 sub-unit sequence of three equine influenza virus isolated in Morocco
Authors: Boukharta Mohamed , Zakham Fathiah , Touil Nadia , Elharrak Mehdi , Ennaji Moulay Mustapha
Published: July 2014

Background

The equine influenza (EI) is an infectious and contagious disease of the upper respiratory tract of horses. Two outbreaks were notified in Morocco during 1997 and 2004 respectively in Nador and Essaouira. The aims of the present study concern the amino acids sequences comparison with reference strain A/equine/Miami/1963(H3N8) of the HA2 subunit including the cleavage site of three equine influenza viruses (H3N8) isolated in Morocco: A/equine/Nador/1/1997(H3N8), A/equine/Essaouira/2/2004 (H3N8) and A/equine/Essaouira/3/2004 (H3N8).

Results

The obtained results demonstrated that the substitutions were located at Ectodomain (ED) and transmembrane domain (TD), and they have only one arginine in cleavage site (HA1-PEKQI-R329-GI-HA2). In the Ectodomain, the mutation N/154
2
/T deleted the NGT glycosylation site at position 154 for both strains A/equine/Essaouira/2/2004(H3N8) and A/equine/Essaouira/3/2004(H3N8). Except for mutation D/1602/Y of the A/equine/Nador/1/1997(H3N8) strain, the other mutations were involved in non conserved sites. While the transmembrane domain (TM) of the strain A/equine/Essaouira/3/2004(H3N8) exhibits a substitution at residue C/199
2
/F. For the A/equine/Nador/1/1997(H3N8) strain the HA2 shows a mutation at residue M/207
2
/L. Three Moroccan strains reveals a common substitution at the residue E/211
2
/Q located between transmembrane domain TM and the cytoplasmic domain (CD).

Conclusion

The given nature virulence of three Moroccan strains, the identified and reported mutations certainly played a permissive role of infection viral process.
Analysis of trainees' memory after classroom presentations of didactical ultrasound courses
Authors: Hempel Dorothea , Stenger Tanja , Campo dell' Orto Marco , Stenger David , Seibel Armin , Röhrig Stefan , Heringer Frank , Walcher Felix , Breitkreutz Raoul
Published: July 2014

Background

Emergency ultrasound is gaining importance in medical education. Widespread teaching methods are frontal presentations and hands-on training. The primary goal of our study was to evaluate the impact of frontal presentations (PS) by analysis of retained knowledge rate (RKR) and learning load (LL).

Methods

Our study was conducted during four introductory courses in emergency ultrasound covering Extended Focused Assessment with Sonography for Trauma (E-FAST) and Focused Echocardiography Evaluation in Life Support (FEEL). Standardized PS (length of 10 to 50 min) were presented by experienced trainers, who were asked to provide keywords, key messages, and images and assign a score to each. Group 1 consisted of 11 medical students with no prior ultrasound experience, and group 2 consisted of 80 physicians. Each group was audience to seven to eight standard PS and requested to answer a free text questionnaire after 0 h, 2.5 h, 24 h, and 14 days.

Results

In group 1, 168/176 questionnaires were analyzed, and 161/202 were analyzed in group 2. RKR in group 1 was 32.5%, 15%, 16%, and 12% at 0 h, 2.5 h, 24 h, and 2 weeks. The physicians' RKR were 23%, 20.5%, and 22.4% after 0, 2.5, and 24 h of a respective PS. The LL was 1.6/min for students and 1.2/min for physicians. There was no difference in RKR when comparing PS with higher and lower LL for both groups; shorter or case-based PS were associated with a higher RKR (p < 0.01).

Conclusions

Our study provides evidence that only a limited amount of information can be processed at a time. Only 12% of knowledge is retained after 2 weeks. Presentations of short duration can increase the retained knowledge rate. Therefore, frontal presentations and classroom-based ultrasound training and teaching should be adapted.
Chemotherapy dose reduction due to chemotherapy induced peripheral neuropathy in breast cancer patients receiving chemotherapy in the neoadjuvant or adjuvant settings: a single-center experience
Authors: Bhatnagar Bhavana , Gilmore Steven , Goloubeva Olga , Pelser Colleen , Medeiros Michelle , Chumsri Saranya , Tkaczuk Katherine , Edelman Martin , Bao Ting
Published: July 2014

Purpose

Taxanes are a cornerstone treatment in early and advanced stage breast cancer and in other common solid tumor malignancies; however, the development of chemotherapy induced peripheral neuropathy (CIPN) often necessitates dose-reduction, which may hamper the effectiveness of the drug and compromise survival outcomes especially when used in the adjuvant setting. Limited literature is available on the prevalence and severity of dose reduction due to CIPN. We sought to determine the frequency and severity of CIPN-induced dose reduction in early stage breast cancer patients who received taxane-based chemotherapy in the neoadjuvant or adjuvant settings.

Methods

We conducted a retrospective single-institution breast cancer clinic chart review of 123 newly diagnosed breast cancer patients and treated with taxane-based neoadjuvant/adjuvant chemotherapy at the University of Maryland Greenebaum Cancer Center between January 2008 and December 2011.

Results

Forty-nine of 123 (40%; 95% CI: 31-49%) patients required dose reduction. Twenty-one (17%; 95% CI: 11-25%) of these patients were dose-reduced specifically due to CIPN that developed during treatment. The median relative dose intensity (received dose/planned dose) for the 21 CIPN-induced dose reduction patients was 73.4% (range, 68.0-94.0%). Patients with diabetes appeared to have a higher risk of taxane-induced dose reduction (p-value=0.01). African-American patients and those treated with paclitaxel (rather than docetaxel) experienced a higher-risk of CIPN-induced dose reduction (p-values are <0.001 and 0.001, respectively).

Conclusions

The incidence of CIPN-associated dose reduction in our patient population was 17%. African-American patients, diabetics and subjects treated with paclitaxel had a higher risk for CIPN-associated dose reduction in our study.
Folate receptor-β constitutes a marker for human proinflammatory monocytes
Authors: Shen Jiayin , Hilgenbrink Andrew R , Xia Wei , Feng Yang , Dimitrov Dimiter S , Lockwood Michael B , Amato Robert J , Low Philip S
Published: July 2014

Activated macrophages are commonly involved in the pathogenesis of inflammatory and autoimmune diseases and have been frequently reported to overexpress FR-β. Although FR-targeted therapies aimed at eliminating activated macrophages have shown promise for treating inflammatory diseases, little work has been performed to evaluate whether other hematopoietic cells might also express FR-β. Analysis of peripheral blood cells with a mAb to human FR-β reveals that only monocytes express FR-β. Molecular characterization of these circulating monocytes further demonstrates that solely the classic/proinflammatory subset (CD14highCD16−) expresses the FR and that only CD14highCD16− FR-β+ monocytes also display the ability to bind folate-linked molecules. Confirmation that this subset of monocytes indeed constitutes the proinflammatory subpopulation was obtained by demonstrating coexpression of FR-β with other proinflammatory markers, including CCR2 and HLA-DR. Synovial monocytes from the joints of patients with RA were also shown to express FR-β. As inhibition of the chemotaxis of proinflammatory monocytes into sites of inflammation has been explored frequently as a means of controlling autoimmune diseases, demonstration that FR-β is uniquely expressed on this proinflammatory subpopulation offers a new strategy to suppress migration of inflammatory monocytes into sites of inflammation.
TLR4 regulates IFN-γ and IL-17 production by both thymic and induced Foxp3+ Tregs during intestinal inflammation
Authors: Cao Anthony T , Yao Suxia , Stefka Andrew T , Liu Zhanju , Qin Hongwei , Liu Houpu , Evans-Marin Heather L , Elson Charles O , Nagler Cathryn R , Cong Yingzi
Published: July 2014

Tregs play a crucial role in the maintenance of intestinal immune homeostasis. However, significant numbers of Foxp3+ Tregs accumulate in the inflamed lesions in experimental colitis and in IBD patients. Treg production of the proinflammatory cytokines IFN-γ and/or IL-17 may arguably explain their ineffectiveness in suppressing intestinal inflammation. However, it remains unknown whether iTreg and tTreg produce proinflammatory cytokines and how TLR signaling regulates this process. Here, we found that Foxp3+Tregs were increased in the intestines of B6.TLR4−/− and B6.IL-10−/− mice when compared with WT B6 mice. TLR4−/− and IL-10−/− resulted in more Tregs within inflamed intestines. The majority of Foxp3+ Tregs in the spleen was Helios+Nrp1+, whereas most Foxp3+ Tregs in the intestinal LP were Helios−Nrp1−. More Helios+Nrp1+ Tregs expressed IFN-γ and/or IL-17 than did Helios−Nrp1− Tregs in the spleen and intestine, which was increased with TLR4−/−. TLR4 signaling in T cells and APCs inhibited Foxp3+ induction via MyD88-dependent, TRIF-independent pathways, which was negatively regulated by SOCS3. Collectively, these data demonstrate Helios+Nrp1+ tTregs and Helios−Nrp1− iTregs produce proinflammatory cytokines in the intestines during inflammation, which was regulated by TLR4 signaling.
Immune control and failure in HCV infection—tipping the balance
Authors: Dustin Lynn B , Cashman Siobhán B , Laidlaw Stephen M
Published: July 2014

Despite the development of potent antiviral drugs, HCV remains a global health problem; global eradication is a long way off. In this review, we discuss the immune response to HCV infection and particularly, the interplay between viral strategies that delay the onset of antiviral responses and host strategies that limit or even eradicate infected cells but also contribute to pathogenesis. Although HCV can disable some cellular virus-sensing machinery, IFN-stimulated antiviral genes are induced in the infected liver. Whereas epitope evolution contributes to escape from T cell-mediated immunity, chronic high antigen load may also blunt the T cell response by activating exhaustion or tolerance mechanisms. The evasive maneuvers of HCV limit sterilizing humoral immunity through rapid evolution of decoy epitopes, epitope masking, stimulation of interfering antibodies, lipid shielding, and cell-to-cell spread. Whereas the majority of HCV infections progress to chronic hepatitis with persistent viremia, at least 20% of patients spontaneously clear the infection. Most of these are protected from reinfection, suggesting that protective immunity to HCV exists and that a prophylactic vaccine may be an achievable goal. It is therefore important that we understand the correlates of protective immunity and mechanisms of viral persistence.
CLIC3 controls recycling of late endosomal MT1-MMP and dictates invasion and metastasis in breast cancer
Authors: Macpherson Iain R , Rainero Elena , Mitchell Louise E , van den Berghe Peter VE , Speirs Claire , Dozynkiewicz Marta A , Chaudhary Suman , Kalna Gabriela , Edwards Joanne , Timpson Paul , Norman Jim C
Published: July 2014

Chloride intracellular channel 3 (CLIC3) drives invasiveness of pancreatic and ovarian cancer by acting in concert with Rab25 to regulate recycling of α5β1 from late endosomes to the plasma membrane. Here we show that in two estrogen receptor (ER)-negative breast cancer cell lines CLIC3 has little influence on integrin recycling, but controls trafficking of the pro-invasive matrix metalloprotease, MT1-MMP. In MDA-MB-231 cells MT1-MMP and CLIC3 are localised primarily to late endosomal/lysosomal compartments located above the plane of adhesion and near the nucleus. MT1-MMP is transferred from these late endosomes to sites of cell-matrix adhesion in a CLIC3-dependent fashion. Correspondingly, CLIC3-knockdown opposes MT1-MMP-dependent invasive processes. These include the disruption of the basement membrane as acini formed from MCF10DCIS.com cells acquire invasive characteristics in 3D culture, and the invasion of MDA-MB-231 cells into Matrigel or organotypic plugs of type I collagen. Consistent with this, expression of CLIC3 predicts poor prognosis in ER-negative breast cancer. The identification of MT1-MMP as a cargo of a CLIC3-regulated pathway that drives invasion highlights the importance of late endosomal sorting and trafficking in breast cancer.
Proteomic analysis unveils a FANCA-modulated neddylation pathway involved in CXCR5 membrane targeting and cell mobility
Authors: Renaudin Xavier , Guervilly Jean-Hugues , Aoufouchi Said , Rosselli Filippo
Published: July 2014

The aim of this study was to identify novel substrates of the FANCcore complex, which inactivation leads to the genetic disorder Fanconi anemia (FA), which associates bone marrow failure, developmental abnormalities and predisposition to cancer. Eight FANC proteins participate in the nuclear FANCcore complex, an E3 ubiquitin-ligase that monoubiquitinates FANCD2 and FANCI in response to replicative stress. Here, we used mass spectrometry to compare proteins from FANCcore complex deficient FA-A and FA-C cells to their ectopically corrected counterparts challenged with hydroxyurea, an inducer of FANCD2 monoubiquitination.

FANCD2 and FANCI appear as the only targets of the FANCcore complex. We identified other proteins post-translationally modified in a FANCA- or FANCC-dependent manner. The majority of these potential targets localizes to the cell membrane. Finally, we demonstrated that (a) the chemokine receptor CXCR5 is neddylated; (b) FANCA, but not FANCC, appears to modulate CXCR5 neddylation through an unknown mechanism; (c) CXCR5 neddylation is involved in targeting the receptor to the cell membrane; and (d) CXCR5 neddylation stimulates cell migration/motility.

Our work has uncovered a pathway involving FANCA in neddylation and cell motility.
Rho/ROCK pathway inhibition by CDK inhibitor p27kip1 participates in the onset of macrophage 3D-mesenchymal migration
Authors: Gui Philippe , Labrousse Arnaud , Van Goethem Emeline , Besson Arnaud , Maridonneau-Parini Isabelle , Le Cabec Véronique
Published: July 2014

Macrophage tissue infiltration can promote tumour development. Depending on the extracellular matrix architecture, macrophages can adopt two migration modes: amoeboid (AM), common to all leukocytes; and mesenchymal (MM), restricted to macrophages and certain tumour cells. Here, we investigated the initiating mechanisms involved in macrophage MM. We show that a single macrophage is able to use both migration modes. Macrophage MM is correlated with a decreased Rho/Rho-associated protein kinase (ROCK) activity and potentiated by ROCK inhibition, suggesting that AM inhibition could participate in MM initiating mechanisms. We identify the cyclin-dependent kinase (CDK) inhibitor p27kip1 as a new effector of macrophage 3D-migration. Using p27kip1 siRNA and p27kip1 mutant mice, we show that p27kip1 promotes MM and hinders AM upstream of the Rho/ROCK pathway, a process associated with a relocation of the protein from the nucleus to the cytoplasm. Finally, we observe that cytoplasmic p27kip1 is required for in vivo macrophage tissue infiltration in induced tumours in mice. This study provides the first evidence that silencing of AM through inhibition of the Rho/ROCK pathway by p27kip1 participates in the onset of macrophage MM.
Septin ring assembly is regulated by Spt20, a structural subunit of SAGA complex
Authors: Lei Bingkun , Zhou Nan , Guo Yuchen , Zhao Wenqi , Tan Yan-Wen , Yu Yao , Lu Hong
Published: July 2014

Accurate cell division requires proper assembly of high-order septin structures. In fission yeast, Spn1-4 are assembled into a primary septin ring at the division site, and the subsequent recruitment of Mid2 to the structure results in a stable septin ring. However, not much is known about the regulation of this key process. Here, we found deletion of Spt20, a structural subunit of SAGA transcriptional activation complex, caused a severe cell separation defect. The defect is mainly due to impaired septin ring assembly, as 80% of spt20Δ cells lost septin rings at the division sites. Spt20 regulates septin ring assembly partially through the transcriptional activation of mid2+. Spt20 also interacts with Spn2 and Mid2 in vitro and is associated with other components of the ring in vivo. Spt20 is co-localized with the septin ring, but does not separate when the septin ring splits. Importantly, Spt20 regulates the stability of the septin ring and is required for the recruitment of Mid2. The transcription-dependent and -independent roles of Spt20 in the septin ring assembly highlight a multifaceted regulation of one process by a SAGA subunit.
Interaction of SQSTM1 with the motor protein dynein: SQSTM1 is required for normal dynein function and trafficking
Authors: Calderilla-Barbosa Luis , Seibenhener M. Lamar , Du Yifeng , Diaz-Meco Maria-Theresa , Moscat Jorge , Yan Jin , Wooten Marie W. , Wooten Michael C.
Published: July 2014

The dynein motor protein complex is required for retrograde transport of vesicular cargo and for transport of aggregated proteins along microtubules for processing and degradation at perinuclear aggresomes. Disruption of this process leads to dysfunctional endosome accumulation and increased protein aggregation in the cell cytoplasm, both pathological features of neurodegenerative diseases. However, the exact mechanism of dynein functionality in these pathways is still being elucidated. Here, we show that the scaffolding protein SQSTM1 directly interacts with dynein through a previously unidentified dynein binding site. This interaction is independent of HDAC6, a known interacting protein of both SQSTM1 and dynein. However, knock-down of HDAC6 increases SQSTM1 interaction with dynein indicating a possible competitive interaction. Using different dynein cargoes we show SQSTM1 is required for proper dynein motility and trafficking along microtubules. Based on our results, we propose a new model of competitive interaction between SQSTM1 and HDAC6 with dynein. In this model, SQSTM1 would not only affect polyubiquitinated protein aggregate and endosomal association with dynein, but would also be required for normal dynein function.
Divergent and convergent roles for kinases and phosphatases in neurofilament dynamics
Authors: Lee Sangmook , Pant Harish C. , Shea Thomas B.
Published: July 2014

C-terminal neurofilament (NF) phosphorylation mediates cation-dependent associations leading to incorporation into the stationary axonal cytoskeleton. Multiple kinases phosphorylate NF-H C-terminal domains, including cyclin-dependent protein kinase 5 (cdk5), mitogen-activated protein kinase (MAPk), casein kinase 1 and 2 (CK1, CK2), glycogen synthase kinase 3 beta (GSK). The respective contributions of these kinases have been confounded since they phosphorylate multiple substrates in addition to NFs and display extensive interaction. Herein, differentiated NB2a/d1 cells were transfected with constructs expressing green fluorescent protein-tagged NF-H, isolated NF-H sidearms and NF-H lacking the distal-most 187 amino acids. Cultures were treated with roscovitine, PD98059, lithium, D4476, tetraBromoBenzoleTriazole, and calyculin, which are active against cdk5, MKK1, GSK, CK1, CK2, and protein phosphatase 1 (PP1), respectively. Sequential phosphorylation by cdk5 and GSK mediated NF-NF associations. MAPk downregulated GSK and CK1 activated PP1, both of which promoted axonal transport and restricted NF-NF associations to axonal neurites. MAPk and cdk5, but not CK1 and GSK, inhibited NF proteolysis. These findings indicate that phosphorylation of NFs by the proline-directed kinases MAPk and cdk5 counterbalance the impact of phosphorylation of NFs by the non-proline-directed CK1 and GSK.
E(y)1/TAF9 mediates the transcriptional output of Notch signaling in Drosophila
Authors: Xie Gengqiang , Yu Zhongsheng , Jia Dongyu , Jiao Renjie , Deng Wu-Min
Published: July 2014

Transcriptional activation of Notch signaling targets requires the formation of a ternary complex that involves the intracellular domain of the Notch receptor (NICD), DNA-binding protein Suppressor of Hairless [Su(H), RPBJ in mammals], and coactivator Mastermind (Mam). Here we report that E(y)1/TAF9, a component of the transcription factor TFIID complex, interacts specifically with the NICD/Su(H)/Mam complex to facilitate the transcriptional output of Notch signaling. We identified E(y)1/TAF9 in a large-scale in vivo RNAi screen for genes involved in a Notch-dependent mitotic-to-endocycle transition in Drosophila follicle cells. Knockdown of e(y)1/TAF9 displayed Notch-like phenotypes and defects in target gene and activity reporter expression in both the follicle cells and wing imaginal discs. Epistatic analyses in these two tissues indicate that E(y)1/TAF9 functions downstream of the Notch cleavage. Biochemical studies in S2 cells demonstrated that E(y)1/TAF9 physically interacts with the transcriptional effectors of Notch signaling, Su(H) and NICD. Together, our data suggest that the association of the NICD/Su(H)/Mastermind complex with E(y)1/TAF9 in response to Notch activation recruits the transcription initiation complex to induce Notch target genes, coupling Notch signaling with the transcriptional machinery.
Genome-wide analysis of trans-splicing in the nematode Pristionchus pacificus unravels conserved gene functions for germline and dauer development in divergent operons
Authors: Sinha Amit , Langnick Claudia , Sommer Ralf J. , Dieterich Christoph
Published: July 2014

Discovery of trans-splicing in multiple metazoan lineages led to the identification of operon-like gene organization in diverse organisms, including trypanosomes, tunicates, and nematodes, but the functional significance of such operons is not completely understood. To see whether the content or organization of operons serves similar roles across species, we experimentally defined operons in the nematode model Pristionchus pacificus. We performed affinity capture experiments on mRNA pools to specifically enrich for transcripts that are trans-spliced to either the SL1- or SL2-spliced leader, using spliced leader–specific probes. We obtained distinct trans-splicing patterns from the analysis of three mRNA pools (total mRNA, SL1 and SL2 fraction) by RNA-seq. This information was combined with a genome-wide analysis of gene orientation and spacing. We could confirm 2219 operons by RNA-seq data out of 6709 candidate operons, which were predicted by sequence information alone. Our gene order comparison of the Caenorhabditis elegans and P. pacificus genomes shows major changes in operon organization in the two species. Notably, only 128 out of 1288 operons in C. elegans are conserved in P. pacificus. However, analysis of gene-expression profiles identified conserved functions such as an enrichment of germline-expressed genes and higher expression levels of operonic genes during recovery from dauer arrest in both species. These results provide support for the model that a necessity for increased transcriptional efficiency in the context of certain developmental processes could be a selective constraint for operon evolution in metazoans. Our method is generally applicable to other metazoans to see if similar functional constraints regulate gene organization into operons.
Case Report: retained gutta-percha as a cause for persistent maxillary sinusitis and pain
Authors: Hodnett Benjamin L. , Ferguson Berrylin
Published: July 2014

Dental sources of infection can produce acute and chronic maxillary sinusitis. In some cases, the source of the infection may be related to the presence of endodontic materials in the oral cavity. In this article, we report a case of retained gutta-percha in the maxillary sinus resulting in chronic sinusitis.
How to Assess Organization’s Financial Standing with Account of Marginal Analysis Results
Authors: Аверина  , Averina Tatyana
Published: July 2014

The paper compares regulatory guidance materials and mathematical models used at various levels to produce integrated assessment of financial standing of organizations. General direction for improving instructional developments in this field is identified, factors influencing development of the appropriate methodical base are described. As one of various integrated assessment techniques ranking survey can be conducted. The paper focuses on properties of economic indicators, used as criteria, provides recommendations on how to conduct ranking assessment. Conclusions concerning appropriateness of sound approach to choosing the method are illustrated with computed examples. The main novelty element within the study is a recommendation to use marginal analysis criteria for assessing financial standing of an organization and probability of its bankruptcy.
Electromagnetic fields do not affect bone micro-architecture in osteoporotic rats
Authors: van der Jagt O. P. , van der Linden J. C. , Waarsing J. H. , Verhaar J. A. N. , Weinans H.
Published: July 2014

Objectives

Electromagnetic fields (EMF) are widely used in musculoskeletal disorders. There are indications that EMF might also be effective in the treatment of osteoporosis. To justify clinical follow-up experiments, we examined the effects of EMF on bone micro-architectural changes in osteoporotic and healthy rats. Moreover, we tested the effects of EMF on fracture healing.

Methods

EMF (20 Gauss) was examined in rats (aged 20 weeks), which underwent an ovariectomy (OVX; n = 8) or sham-ovariectomy (sham-OVX; n = 8). As a putative positive control, all rats received bilateral fibular osteotomies to examine the effects on fracture healing. Treatment was applied to one proximal lower leg (three hours a day, five days a week); the lower leg was not treated and served as a control. Bone architectural changes of the proximal tibia and bone formation around the osteotomy were evaluated using in vivo microCT scans at start of treatment and after three and six weeks.

Results

In both OVX and sham-OVX groups, EMF did not result in cancellous or cortical bone changes during follow-up. Moreover, EMF did not affect the amount of mineralised callus volume around the fibular osteotomy.

Conclusions

In this study we were unable to reproduce the strong beneficial findings reported by others. This might indicate that EMF treatment is very sensitive to the specific set-up, which would be a serious hindrance for clinical use. No evidence was found that EMF treatment can influence bone mass for the benefit of osteoporotic patients. Cite this article: Bone Joint Res 2014;3:230–5.
Availability of Structured and Unstructured Clinical Data for Comparative
Effectiveness Research and Quality Improvement: A Multi-Site Assessment
Authors: Capurro Daniel , Yetisgen Meliha , Eaton Erik , Black Robert , Tarczy-Hornoch Peter
Published: July 2014

Introduction: A key attribute of a learning health care system is the ability to
collect and analyze routinely collected clinical data in order to quickly generate new
clinical evidence, and to monitor the quality of the care provided. To achieve this
vision, clinical data must be easy to extract and stored in computer readable formats.
We conducted this study across multiple organizations to assess the availability of such
data specifically for comparative effectiveness research (CER) and quality improvement
(QI) on surgical procedures.Setting: This study was conducted in the context of the data
needed for the already established Surgical Care and Outcomes Assessment Program
(SCOAP), a clinician-led, performance benchmarking, and QI registry for surgical and
interventional procedures in Washington State.Methods: We selected six hospitals,
managed by two Health Information Technology (HIT) groups, and assessed the ease of
automated extraction of the data required to complete the SCOAP data collection forms.
Each data element was classified as easy, moderate, or complex to
extract.Results: Overall, a significant proportion of the data required to automatically
complete the SCOAP forms was not stored in structured computer-readable formats, with
more than 75 percent of all data elements being classified as moderately complex or
complex to extract. The distribution differed significantly between the health care
systems studied.Conclusions: Although highly desirable, a learning health care system
does not automatically emerge from the implementation of electronic health records
(EHRs). Innovative methods to improve the structured capture of clinical data are needed
to facilitate the use of routinely collected clinical data for patient
phenotyping.
Wage Slavery, Oriental Despotism, and Global Labor Management in Maria Edgeworth’s Popular Tales
Authors: Cohen Ashley L.
Published: July 2014

Maria Edgeworth’s short story collection Popular Tales (1804) includes strikingly similar scenes of slavery set in Jamaica, India, and England. This essay resists the tendency to view such scenes as mimetic representations of historical practices of human bondage, and instead argues that the resemblance between Edgeworth’s portrayals of slavery in Jamaica, India, and Cornwall is best understood as an expression of the historical linkages between these regions in the context of what I call the “global Jacobin crisis” of the 1790s.
Order and Resistance in the Polemical and Catechetical Literature of Early Modern Spain (1515–1599): Christians, Muslims, and Moriscos
Authors: Busic Jason
Published: July 2014

This article addresses four works written for the instruction of Muslims and Moriscos in early modern Spain within the framework of negotiation of power and identities. Through Juan Andrés’s Confusión (1515), Juan Luis Vives’s “Contra sectam Mahometi” (1543), Pedro Guerra de Lorca’s Catecheses mystagogicae (1586), and Juan de Ribera’s Catechismo (1599), it asks how these texts attempt to impose order in an Iberia characterized by heterogeneity. It also asks how the tension between the goals of the corpus and its cultural context surfaces within their pages. The article argues that these texts are not simply an elitist literature reflecting a desire opposed to reality (i.e., religious and cultural homogeneity), but a reflection of their religious and cultural circumstances.
Ghostly Landscapes: Soviet Liberators Photograph the Holocaust
Authors: Shneer David
Published: July 2014

In the West, Auschwitz and its gas chambers became a metonym of genocide, but genocide takes place less often in purpose-built death centers than in mundane sites of daily existence, like “killing fields” in Cambodia or by the sides of roads in Rwanda. So too with the Holocaust. In the Soviet Union, the Holocaust was more mundane, integrated into daily life under Nazi occupation. Because of this, the absence documented in Soviet Holocaust liberation photography better reflects the experience of genocide than the human drama of survival captured in American and British photography. In these mundane, haunting, and sublime images, Soviet photographers have unwittingly captured the story of genocide—ghostly landscapes haunted by the dead, not the living.
“Democratic Development” in Neoliberal Drag
Authors: Simpson Bradley R.
Published: July 2014

This review examines the book Contesting Development: Participatory Projects and Local Conflict Dynamics in Indonesia, an impact study of the widely lauded Kecamatan Development Program (KDP). The authors argue that KDP contributes to greater accountability, transparency, civic engagement—especially by previously marginalized populations—and nonviolent conflict resolution in areas where it is operating well, primarily through indirect feedback mechanisms poorly accounted for in the traditional economic metrics for evaluating such programs. The review suggests that the authors remain wedded to a set of neoliberal assumptions about development and insufficiently historicize the program’s origins and role in Indonesian politics.
Science, Theology, and the Simplicity of Chant: Victorian Musicology at War
Authors: Zon Bennett
Published: July 2014

There were two kinds of chant in Victorian Britain - one theological, the other scientific: Gregorian chant, the traditional music of the church; and primitive chant, the earliest human music. Because of their rudimentary nature Victorians described them as 'simple'. This essay explores how science and theology used simplicity to help define themselves through chant. It begins with an exploration of the 'war' between the two disciplines; then examines the meaning each discipline ascribes to simplicity and chant; and concludes with a reflection on the nature of their 'peace' and its implications for the history of musicology.