bluuebunny/crossref_metadata_2025 huggingface dataset:
Coxa vara with proximal femoral growth arrest as a possible consequence of extracorporeal membrane oxygenation: a case report
Authors: Pretell Mazzini Juan , Rodríguez Martín Juan , Marti Ciruelos Rafael
Published: July 2012

Coxa vara is an abnormality of the proximal femur with a decreased neck-shaft angle and resulting leg-length discrepancy, has been associated with conditions such as congenital coxa vara, traumatic injury, sepsis, rickets, vascular damage, or metabolic disorders; however its possible relationship with extracorporeal membrane oxygenation has been recently reported.

A full term girl was born with a total infradiaphragmatic anomalous pulmonary venous drainage, at the age of 12 days, an anastomosis of the pulmonary venous trunk with the left auricle and closure of the auricular septal defect was performed; during this procedure extracorporeal membrane oxygenation was used during 104 minutes, no neonatal sepsis was developed. She had no orthopedic issues until she was 3 years and 10 months old, when she presented with limp related to the right lower limb, with no pain. She had a leg-length discrepancy of 2 cm (right - left), limited right hip abduction to 25°, and internal rotation to 5°, also had a positive Trendelenburg test. No flexion/extension abnormalities. Anteroposterior radiographs and magnetic resonance revealed coxa vara with proximal femoral growth arrest. A valgus osteotomy with greater trochanteric epiphysiodesis was performed. At the eight month follow-up, she had no hip pain, better hip range of motion, no difficulties with recreational activities and the osteotomy healed.

Another four similar cases had been reported with similar outcome, we think that it will be recommendable to take images in patients with this background and limb leg-length discrepancy or abnormal range of motion.
SMS reminders- future in self-care management of diabetes mellitus?
Authors: Riaz Talha , Riaz Haris , Hussain Syed A , Kherani Danish
Published: July 2012

Application of SMS in reminders of medical appointments and delivering medical tests is not new, however its focus on clinical interventions has just begun. Usage of tailored SMS reminders to increase adherence in treatment programs among sick individuals has allowed an interventional role in self-care management of Diabetes Mellitus (DM).
HER2 Amplification Has no Prognostic Value in Sporadic and Hereditary Ovarian Tumours
Authors: Brożek Izabela , Kardaś Iwona , Ochman Karolina , Dębniak Jarosław , Stukan Maciej , Ratajska Magdalena , Morzuch Lucyna , Emerich Janusz , Limon Janusz
Published: July 2012

Whereas HER2 amplification is a well-known phenomenon in breast tumours, its frequency and clinical importance in ovarian cancer have not been established. The aim of the study was to compare the frequency of HER2 amplification in hereditary (BRCA-positive) and sporadic (BRCA-negative) ovarian tumours and to estimate the association of this gene alteration on clinical outcome in ovarian cancer patients. We analysed HER2 amplification in 53 ovarian tumours: 20 from mutation carriers (18 in BRCA1 and 2 in BRCA2 gene) and 33 from non-carriers. Fluorescence in situ hybridization for HER2 was performed on 'touch' slides from frozen tumour samples or formalin-fixed, paraffin-embedded tissue. Our results indicate that high amplification (HER2: centromere ratio>5) is an infrequent phenomenon in ovarian tumours (6/53 cases). It occurs in both hereditary (4/20) and sporadic (2/33) tumours and no difference in the frequency of HER2 amplification exists between these groups. There is no significant difference in the clinical outcome of patients with HER2 amplified and non-amplified tumours (p = 0.3). Our results suggest a different biological role of HER2 amplification in ovarian and breast cancer.
Strategies to promote reporting of Surgical Care Improvement Project (SCIP) measures: a pilot survey of anesthesia department leaders
Authors: Speck Rebecca M , Neuman Mark D , Bond Andrew R , Fleisher Lee A
Published: July 2012

Background

The Surgical Care Improvement Project (SCIP) is a quality improvement initiative focused on reducing surgical complications. Reporting SCIP performance measures helps determine whether hospitals receive the full payment update from the Centers for Medicare and Medicaid Services. Strategies in use by hospitals to motivate departmental participation in SCIP reporting are poorly understood.

Methods

A 12-item pilot survey exploring strategies to promote reporting of SCIP measures was developed and mailed to department of anesthesiology chairs at 1,426 US hospitals. Descriptive statistics and χ
2 analysis were used to summarize respondent and survey data.

Results

In all, 29.5% of the sample responded to the survey, with 96.9% indicating SCIP participation; 62.5% participated primarily for voluntary reasons, and 4.2% reported an incentive from their hospital as the primary reason for participation.

Conclusions

Hospital strategies promoting physician participation in SCIP currently vary. A minority of survey respondents indicated that an incentive was used to encourage adherence to SCIP measures. Further research to optimize such strategies may support future efforts to improve perioperative care.
Gene profiling in white blood cells predicts infliximab responsiveness in rheumatoid arthritis
Authors: Lequerré Thierry , Gauthier-Jauneau Anne-Christine , Bansard Carine , Derambure Céline , Hiron Martine , Vittecoq Olivier , Daveau Maryvonne , Mejjad Othmane , Daragon Alain , Tron François , Le Loët Xavier , Salier Jean-Philippe
Published: July 2012

As indicators of responsiveness to a tumour necrosis factor (TNF)α blocking agent (infliximab) are lacking in rheumatoid arthritis, we have used gene profiling in peripheral blood mononuclear cells to predict a good versus poor response to infliximab. Thirty three patients with very active disease (Disease Activity Score 28 >5.1) that resisted weekly methotrexate therapy were given infliximab at baseline, weeks 2 and 6, and every 8th week thereafter. The patients were categorized as responders if a change of Disease Activity Score 28 = 1.2 was obtained at 3 months. Mononuclear cell RNAs were collected at baseline and at three months from responders and non-responders. The baseline RNAs were hybridised to a microarray of 10,000 non-redundant human cDNAs. In 6 responders and 7 non-responders, 41 mRNAs identified by microarray analysis were expressed as a function of the response to treatment and an unsupervised hierarchical clustering perfectly separated these responders from non-responders. The informativeness of 20 of these 41 transcripts, as measured by qRT-PCR, was re-assessed in 20 other patients. The combined levels of these 20 transcripts properly classified 16 out of 20 patients in a leave-one-out procedure, with a sensitivity of 90% and a specificity of 70%, whereas a set of only 8 transcripts properly classified 18/20 patients. Trends for changes in various transcript levels at three months tightly correlated with treatment responsiveness and a down-regulation of specific transcript levels was observed in non-responders only. Our gene profiling obtained by a non-invasive procedure should now be used to predict the likely responders to an infliximab/methotrexate combination.
Dissection of a locus on mouse chromosome 5 reveals arthritis promoting and inhibitory genes
Authors: Lindvall Therese , Karlsson Jenny , Holmdahl Rikard , Andersson Åsa
Published: July 2012

Introduction

In a cross between two mouse strains, the susceptible B10.RIII (H-2r) and resistant RIIIS/J (H-2r) strains, a locus on mouse chromosome 5 (Eae39) was previously shown to control experimental autoimmune encephalomyelitis (EAE). Recently, quantitative trait loci (QTL), linked to disease in different experimental arthritis models, were mapped to this region. The aim of the present study was to investigate whether genes within Eae39, in addition to EAE, control development of collagen-induced arthritis (CIA).

Methods

CIA, induced by immunisation with bovine type II collagen, was studied in Eae39 congenic and sub-interval congenic mice. Antibody titres were investigated with ELISA. Gene-typing was performed by micro-satellite mapping and statistics was calculated by standard methods.

Results

Experiments of CIA in Eae39 congenic- and sub-interval congenic mice, carrying RIIIS/J genes on the B10.RIII genetic background, revealed three loci within Eae39 that control disease and anti-collagen antibody titres. Two of the loci promoted disease and the third locus was protected against CIA development. By further breeding of mice with small congenic fragments, we identified a 3.2 mega base pair (Mbp) interval that regulates disease.

Conclusions

Disease-promoting and disease-protecting genes within the Eae39 locus on mouse chromosome 5 control susceptibility to CIA. A disease-protecting locus in the telomeric part of Eae39 results in lower anti-collagen antibody responses. The study shows the importance of breeding sub-congenic mouse strains to reveal genetic effects on complex diseases.
High frequency of corticosteroid and immunosuppressive therapy in patients with systemic sclerosis despite limited evidence for efficacy
Authors: Hunzelmann Nicolas , Moinzadeh Pia , Genth Ekkehard , Krieg Thomas , Lehmacher Walter , Melchers Inga , Meurer Michael , Müller-Ladner Ulf , Olski Thorsten M , Pfeiffer Christiane , Riemekasten Gabriela , Schulze-Lohoff Eckhard , Sunderkoetter Cord , Weber Manfred ,   the German Network for Systemic Scleroderma Centers
Published: July 2012

Introduction

In systemic sclerosis (SSc) little evidence for the effectiveness of anti-inflammatory and immunosuppressive therapy exists. The objective of this study was to determine the extent to which SSc patients are treated with corticosteroids and immunosuppressive agents.

Methods

Data on duration and dosage of corticosteroids and on the type of immunosuppressive agent were analyzed from 1,729 patients who were registered in the German Network for Systemic Scleroderma (DNSS).

Results

A total 41.3% of all registered SSc patients was treated with corticosteroids. Corticosteroid use was reported in 49.1% of patients with diffuse cutaneous SSc and 31.3% of patients with limited cutaneous SSc (P < 0.0001). Among patients with overlap disease characteristics, 63.5% received corticosteroids (P < 0.0001 vs. limited cutaneous SSc). A total 16.1% of the patients received corticosteroids with a daily dose ≥ 15 mg prednisone equivalent. Immunosuppressive therapy was prescribed in 35.8% of patients. Again, among those patients with overlap symptoms, a much higher proportion (64.1%) was treated with immunosuppressive agents, compared with 46.4% of those with diffuse cutaneous SSc sclerosis and 22.2% of those with limited cutaneous SSc (P < 0.0001). The most commonly prescribed drugs were methotrexate (30.5%), cyclophosphamide (22.2%), azathioprine (21.8%) and (hydroxy)chloroquine (7.2%). The use of these compounds varied significantly between medical subspecialties.

Conclusions

Despite limited evidence for the effectiveness of corticosteroids and immunosuppressive agents in SSc, these potentially harmful drugs are frequently prescribed to patients with all forms of SSc. Therefore, this study indicates the need to develop and communicate adequate treatment recommendations.
Testing for the association of the KIAA1109/Tenr/IL2/IL21gene region with rheumatoid arthritis in a European family-based study
Authors: Teixeira Vitor Hugo , Pierlot Celine , Migliorini Paola , Balsa Alejandro , Westhovens René , Barrera Pilar , Alves Helena , Vaz Carlos , Fernandes Manuela , Pascual-Salcedo Dora , Bombardieri Stefano , Dequeker Jan , Radstake Timothy R , Van Riel Piet , van de Putte Leo , Lopes-Vaz Antonio , Bardin Thomas , Prum Bernard , Cornélis François , Petit-Teixeira Elisabeth ,   the European Consortium on Rheumatoid Arthritis Families
Published: July 2012

Introduction

A candidate gene approach, in a large case–control association study in the Dutch population, has shown that a 480 kb block on chromosome 4q27 encompassing KIAA1109/Tenr/IL2/IL21 genes is associated with rheumatoid arthritis. Compared with case–control association studies, family-based studies have the added advantage of controlling potential differences in population structure. Therefore, our aim was to test this association in populations of European origin by using a family-based approach.

Methods

A total of 1,302 West European white individuals from 434 trio families were genotyped for the rs4505848, rs11732095, rs6822844, rs4492018 and rs1398553 polymorphisms using the TaqMan Allelic discrimination assay (Applied Biosystems). The genetic association analyses for each SNP and haplotype were performed using the Transmission Disequilibrium Test and the genotype relative risk.

Results

We observed evidence for association of the heterozygous rs4505848-AG genotype with rheumatoid arthritis (P = 0.04); however, no significance was found after Bonferroni correction. In concordance with previous findings in the Dutch population, we observed a trend of undertransmission for the rs6822844-T allele and rs6822844-GT genotype to rheumatoid arthritis patients. We further investigated the five SNP haplotypes of the KIAA1109/Tenr/IL2/IL21 gene region. We observed, as described in the Dutch population, a nonsignificant undertransmission of the AATGG haplotype to rheumatoid arthritis patients.

Conclusions

Using a family-based study, we have provided a trend for the association of the KIAA1109/Tenr/IL2/IL21 gene region with rheumatoid arthritis in populations of European descent. Nevertheless, we failed to replicate a significant association of this region in our rheumatoid arthritis family sample. Further investigation of this region, including detection and testing of all variants, is required to confirm rheumatoid arthritis association.
Replication of recently identified systemic lupus erythematosus genetic associations: a case–control study
Authors: Suarez-Gestal Marian , Calaza Manuel , Endreffy Emöke , Pullmann Rudolf , Ordi-Ros Josep , Sebastiani Gian Domenico , Ruzickova Sarka , Jose Santos Maria , Papasteriades Chryssa , Marchini Maurizio , Skopouli Fotini N , Suarez Ana , Blanco Francisco J , D'Alfonso Sandra , Bijl Marc , Carreira Patricia , Witte Torsten , Migliaresi Sergio , Gomez-Reino Juan J , Gonzalez Antonio ,   the European Consortium of SLE DNA Collections
Published: July 2012

Introduction

We aimed to replicate association of newly identified systemic lupus erythematosus (SLE) loci.

Methods

We selected the most associated SNP in 10 SLE loci. These 10 SNPs were analysed in 1,579 patients with SLE and 1,726 controls of European origin by single-base extension. Comparison of allele frequencies between cases and controls was done with the Mantel–Haenszel approach to account for heterogeneity between sample collections.

Results

A previously controversial association with a SNP in the TYK2 gene was replicated (odds ratio (OR) = 0.79, P = 2.5 × 10-5), as well as association with the X chromosome MECP2 gene (OR = 1.26, P = 0.00085 in women), which had only been reported in a single study, and association with four other loci, 1q25.1 (OR = 0.81, P = 0.0001), PXK (OR = 1.19, P = 0.0038), BANK1 (OR = 0.83, P = 0.006) and KIAA1542 (OR = 0.84, P = 0.001), which have been identified in a genome-wide association study, but not found in any other study. All these replications showed the same disease-associated allele as originally reported. No association was found with the LY9 SNP, which had been reported in a single study.

Conclusions

Our results confirm nine SLE loci. For six of them, TYK2, MECP2, 1q25.1, PXK, BANK1 and KIAA1542, this replication is important. The other three loci, ITGAM, STAT4 and C8orf13-BLK, were already clearly confirmed. Our results also suggest that MECP2 association has no influence in the sex bias of SLE, contrary to what has been proposed. In addition, none of the other associations seems important in this respect.
Interleukin-17A upregulates receptor activator of NF-κB on osteoclast precursors
Authors: Adamopoulos Iannis E , Chao Cheng-chi , Geissler Richard , Laface Drake , Blumenschein Wendy , Iwakura Yoichiro , McClanahan Terrill , Bowman Edward P
Published: July 2012

Introduction

The interaction between the immune and skeletal systems is evidenced by the bone loss observed in autoimmune diseases such as rheumatoid arthritis. In this paper we describe a new mechanism by which the immune cytokine IL-17A directly affects osteoclastogenesis.

Methods

Human CD14+ cells were isolated from healthy donors, cultured on dentine slices and coverslips and stimulated with IL-17A and/or receptor activator of NF-κB ligand (RANKL). Osteoclast differentiation was evaluated by gene expression, flow cytometry, tartrate-resistant acid phosphatase staining, fluorescence and electron microscopy. Physiologic bone remodelling was studied in wild-type (Wt) and IL-17A-/- mice using micro-computer tomography and serum RANKL/osteoprotegerin concentration. Functional osteoclastogenesis assays were performed using bone marrow macrophages isolated from IL-17A-/- and Wt mice.

Results

IL-17A upregulates the receptor activator for NF-κB receptor on human osteoclast precursors in vitro, leading to increased sensitivity to RANKL signalling, osteoclast differentiation and bone loss. IL-17A-/- mice have physiological bone homeostasis indistinguishable from Wt mice, and bone marrow macrophages isolated from these mice develop fully functional normal osteoclasts.

Conclusions

Collectively our data demonstrate anti-IL-17A treatment as a selective therapeutic target for bone loss associated with autoimmune diseases.
Transglutaminase 2 cross-linking activity is linked to invadopodia formation and cartilage breakdown in arthritis
Authors: Lauzier Annie , Charbonneau Martine , Paquette Marilène , Harper Kelly , Dubois Claire M
Published: July 2012

Introduction

The microenvironment surrounding inflamed synovium leads to the activation of fibroblast-like synoviocytes (FLSs), which are important contributors to cartilage destruction in rheumatoid arthritic (RA) joints. Transglutaminase 2 (TG2), an enzyme involved in extracellular matrix (ECM) cross-linking and remodeling, is activated by inflammatory signals. This study was undertaken to assess the potential contribution of TG2 to FLS-induced cartilage degradation.

Methods

Transglutaminase (TGase) activity and collagen degradation were assessed with the immunohistochemistry of control, collagen-induced arthritic (CIA) or TG2 knockdown (shRNA)-treated joint tissues. TGase activity in control (C-FLS) and arthritic (A-FLS) rat FLSs was measured by in situ 5-(biotinamido)-pentylamine incorporation. Invadopodia formation and functions were measured in rat FLSs and cells from normal (control; C-FLS) and RA patients (RA-FLS) by in situ ECM degradation. Immunoblotting, enzyme-linked immunosorbent assay (ELISA), and p3TP-Lux reporter assays were used to assess transforming growth factor-β (TGF-β) production and activation.

Results

TG2 and TGase activity were associated with cartilage degradation in CIA joints. In contrast, TGase activity and cartilage degradation were reduced in joints by TG2 knockdown. A-FLSs displayed higher TGase activity and TG2 expression in ECM than did C-FLSs. TG2 knockdown or TGase inhibition resulted in reduced invadopodia formation in rat and human arthritic FLSs. In contrast, increased invadopodia formation was noted in response to TGase activity induced by TGF-β, dithiothreitol (DTT), or TG2 overexpression. TG2-induced increases in invadopodia formation were blocked by TGF-β neutralization or inhibition of TGF-βR1.

Conclusions

TG2, through its TGase activity, is required for ECM degradation in arthritic FLS and CIA joints. Our findings provide a potential target to prevent cartilage degradation in RA.
Expression of Six1 in luminal breast cancers predicts poor prognosis and promotes increases in tumor initiating cells by activation of extracellular signal-regulated kinase and transforming growth factor-beta signaling pathways
Authors: Iwanaga Ritsuko , Wang Chu-An , Micalizzi Douglas S , Harrell J Chuck , Jedlicka Paul , Sartorius Carol A , Kabos Peter , Farabaugh Susan M , Bradford Andrew P , Ford Heide L
Published: July 2012

Introduction

Mammary-specific overexpression of Six1 in mice induces tumors that resemble human breast cancer, some having undergone epithelial to mesenchymal transition (EMT) and exhibiting stem/progenitor cell features. Six1 overexpression in human breast cancer cells promotes EMT and metastatic dissemination. We hypothesized that Six1 plays a role in the tumor initiating cell (TIC) population specifically in certain subtypes of breast cancer, and that by understanding its mechanism of action, we could potentially develop new means to target TICs.

Methods

We examined gene expression datasets to determine the breast cancer subtypes with Six1 overexpression, and then examined its expression in the CD24low/CD44+ putative TIC population in human luminal breast cancers xenografted through mice and in luminal breast cancer cell lines. Six1 overexpression, or knockdown, was performed in different systems to examine how Six1 levels affect TIC characteristics, using gene expression and flow cytometric analysis, tumorsphere assays, and in vivo TIC assays in immunocompromised and immune-competent mice. We examined the molecular pathways by which Six1 influences TICs using genetic/inhibitor approaches in vitro and in vivo. Finally, we examined the expression of Six1 and phosphorylated extracellular signal-regulated kinase (p-ERK) in human breast cancers.

Results

High levels of Six1 are associated with adverse outcomes in luminal breast cancers, particularly the luminal B subtype. Six1 levels are enriched in the CD24low/CD44+ TIC population in human luminal breast cancers xenografted through mice, and in tumorsphere cultures in MCF7 and T47D luminal breast cancer cells. When overexpressed in MCF7 cells, Six1expands the TIC population through activation of transforming growth factor-beta (TGF-β) and mitogen activated protein kinase (MEK)/ERK signaling. Inhibition of ERK signaling in MCF7-Six1 cells with MEK1/2 inhibitors, U0126 and AZD6244, restores the TIC population of luminal breast cancer cells back to that observed in control cells. Administration of AZD6244 dramatically inhibits tumor formation efficiency and metastasis in cells that express high levels of Six1 ectopically or endogenously. Finally, we demonstrate that Six1 significantly correlates with phosphorylated ERK in human breast cancers.

Conclusions

Six1 plays an important role in the TIC population in luminal breast cancers and induces a TIC phenotype by enhancing both TGF-β and ERK signaling. MEK1/2 kinase inhibitors are potential candidates for targeting TICs in breast tumors.
Pro-adrenomedullin to predict severity and outcome in community-acquired pneumonia [ISRCTN04176397]
Authors: Christ-Crain Mirjam , Morgenthaler Nils G , Stolz Daiana , Müller Christian , Bingisser Roland , Harbarth Stephan , Tamm Michael , Struck Joachim , Bergmann Andreas , Müller Beat
Published: July 2012

Introduction

Pro-adrenomedullin (proADM) is helpful for individual risk assessment and outcome prediction in sepsis. A major cause of sepsis is community-acquired pneumonia (CAP). The aim of this study was to investigate the value of proADM levels for severity assessment and outcome prediction in CAP.

Methods

Data from 302 patients admitted to the emergency department with CAP were included in a prospective observational study. Procalcitonin, C-reactive protein levels, leukocyte count, clinical variables and the pneumonia severity index (PSI) were measured. ProADM levels were measured with a new sandwich immunoassay for mid regional ProADM (MR-proADM, Brahms AG, Hennigsdorf/Berlin, Germany).

Results

ProADM levels, in contrast to C-reactive protein and leukocyte count, increased with increasing severity of CAP, classified according to the PSI score (ANOVA, p < 0.001). In patients who died during follow-up, proADM levels on admission were significantly higher compared to levels in survivors (2.1 (1.5 to 3.0) versus 1.0 (0.6 to 1.6) nmol/l, p < 0.001). In a receiver operating characteristic (ROC) analysis for survival, the area under the ROC curve (AUC) for proADM was 0.76 (95% confidence interval (CI) 0.71–0.81), which was significantly higher compared to procalcitonin (p = 0.004), C-reactive protein (p < 0.001) and total leukocyte count (p = 0.001) and similar to the AUC of the PSI (0.73, p = 0.54). A clinical model including the PSI and proADM increased the prognostic accuracy to predict failure compared to a model relying on the PSI alone (AUC, 0.77 (0.70 to 0.84), p = 0.03).

Conclusion

ProADM, as a novel biomarker, is a useful tool for the risk stratification of patients with CAP.
Regulation of dynein localization and centrosome positioning by Lis-1 and asunder during Drosophila spermatogenesis
Authors: Sitaram Poojitha , Anderson Michael A. , Jodoin Jeanne N. , Lee Ethan , Lee Laura A.
Published: July 2012

Dynein, a microtubule motor complex, plays crucial roles in cell-cycle progression in many systems. The LIS1 accessory protein directly binds dynein, although its precise role in regulating dynein remains unclear. Mutation of human LIS1 causes lissencephaly, a developmental brain disorder. To gain insight into the in vivo functions of LIS1, we characterized a male-sterile allele of the Drosophila homolog of human LIS1. We found that centrosomes do not properly detach from the cell cortex at the onset of meiosis in most Lis-1 spermatocytes; centrosomes that do break cortical associations fail to attach to the nucleus. In Lis-1 spermatids, we observed loss of attachments between the nucleus, basal body and mitochondria. The localization pattern of LIS-1 protein throughout Drosophila spermatogenesis mirrors that of dynein. We show that dynein recruitment to the nuclear surface and spindle poles is severely reduced in Lis-1 male germ cells. We propose that Lis-1 spermatogenesis phenotypes are due to loss of dynein regulation, as we observed similar phenotypes in flies null for Tctex-1, a dynein light chain. We have previously identified asunder (asun) as another regulator of dynein localization and centrosome positioning during Drosophila spermatogenesis. We now report that Lis-1 is a strong dominant enhancer of asun and that localization of LIS-1 in male germ cells is ASUN dependent. We found that Drosophila LIS-1 and ASUN colocalize and coimmunoprecipitate from transfected cells, suggesting that they function within a common complex. We present a model in which Lis-1 and asun cooperate to regulate dynein localization and centrosome positioning during Drosophila spermatogenesis.
Absence of Dpy19l2, a new inner nuclear membrane protein, causes globozoospermia in mice by preventing the anchoring of the acrosome to the nucleus
Authors: Pierre Virginie , Martinez Guillaume , Coutton Charles , Delaroche Julie , Yassine Sandra , Novella Caroline , Pernet-Gallay Karin , Hennebicq Sylviane , Ray Pierre F. , Arnoult Christophe
Published: July 2012

Sperm-head elongation and acrosome formation, which take place during the last stages of spermatogenesis, are essential to produce competent spermatozoa that are able to cross the oocyte zona pellucida and to achieve fertilization. During acrosome biogenesis, acrosome attachment and spreading over the nucleus are still poorly understood and to date no proteins have been described to link the acrosome to the nucleus. We recently demonstrated that a deletion of DPY19L2, a gene coding for an uncharacterized protein, was responsible for a majority of cases of type I globozoospermia, a rare cause of male infertility that is characterized by the exclusive production of round-headed acrosomeless spermatozoa. Here, using Dpy19l2 knockout mice, we describe the cellular function of the Dpy19l2 protein. We demonstrate that the protein is expressed predominantly in spermatids with a very specific localization restricted to the inner nuclear membrane facing the acrosomal vesicle. We show that the absence of Dpy19l2 leads to the destabilization of both the nuclear dense lamina (NDL) and the junction between the acroplaxome and the nuclear envelope. Consequently, the acrosome and the manchette fail to be linked to the nucleus leading to the disruption of vesicular trafficking, failure of sperm nuclear shaping and eventually to the elimination of the unbound acrosomal vesicle. Finally, we show for the first time that Dpy19l3 proteins are also located in the inner nuclear envelope, therefore implying that the Dpy19 proteins constitute a new family of structural transmembrane proteins of the nuclear envelope.
Hypoxia promotes satellite cell self-renewal and enhances the efficiency of myoblast transplantation
Authors: Liu Weiyi , Wen Yefei , Bi Pengpeng , Lai Xinsheng , Liu X. Shawn , Liu Xiaoqi , Kuang Shihuan
Published: July 2012

Microenvironmental oxygen (O2) regulates stem cell activity, and a hypoxic niche with low oxygen levels has been reported in multiple stem cell types. Satellite cells are muscle-resident stem cells that maintain the homeostasis and mediate the regeneration of skeletal muscles. We demonstrate here that hypoxic culture conditions favor the quiescence of satellite cell-derived primary myoblasts by upregulating Pax7, a key regulator of satellite cell self-renewal, and downregulating MyoD and myogenin. During myoblast division, hypoxia promotes asymmetric self-renewal divisions and inhibits asymmetric differentiation divisions without affecting the overall rate of proliferation. Mechanistic studies reveal that hypoxia activates the Notch signaling pathway, which subsequently represses the expression of miR-1 and miR-206 through canonical Hes/Hey proteins, leading to increased levels of Pax7. More importantly, hypoxia conditioning enhances the efficiency of myoblast transplantation and the self-renewal of implanted cells. Given the robust effects of hypoxia on maintaining the quiescence and promoting the self-renewal of cultured myoblasts, we predict that oxygen levels in the satellite cell niche play a central role in precisely balancing quiescence versus activation, and self-renewal versus differentiation, in muscle stem cells in vivo.
Signalling from hindbrain boundaries regulates neuronal clustering that patterns neurogenesis
Authors: Terriente Javier , Gerety Sebastian S. , Watanabe-Asaka Tomomi , Gonzalez-Quevedo Rosa , Wilkinson David G.
Published: July 2012

During central nervous system development, neural progenitors are patterned to form discrete neurogenic and non-neurogenic zones. In the zebrafish hindbrain, neurogenesis is organised by Fgf20a emanating from neurons located at each segment centre that inhibits neuronal differentiation in adjacent progenitors. Here, we have identified a molecular mechanism that clusters fgf20a-expressing neurons in segment centres and uncovered a requirement for this positioning in the regulation of neurogenesis. Disruption of hindbrain boundary cell formation alters the organisation of fgf20a-expressing neurons, consistent with a role of chemorepulsion from boundaries. The semaphorins Sema3fb and Sema3gb, which are expressed by boundary cells, and their receptor Nrp2a are required for clustering of fgf20a-expressing neurons at segment centres. The dispersal of fgf20a-expressing neurons that occurs following the disruption of boundaries or of Sema3fb/Sema3gb signalling leads to reduced FGF target gene expression in progenitors and an increased number of differentiating neurons. Sema3 signalling from boundaries thus links hindbrain segmentation to the positioning of fgf20a-expressing neurons that regulates neurogenesis.
Multiscale mechanisms of cell migration during development: theory and experiment
Authors: McLennan Rebecca , Dyson Louise , Prather Katherine W. , Morrison Jason A. , Baker Ruth E. , Maini Philip K. , Kulesa Paul M.
Published: July 2012

Long-distance cell migration is an important feature of embryonic development, adult morphogenesis and cancer, yet the mechanisms that drive subpopulations of cells to distinct targets are poorly understood. Here, we use the embryonic neural crest (NC) in tandem with theoretical studies to evaluate model mechanisms of long-distance cell migration. We find that a simple chemotaxis model is insufficient to explain our experimental data. Instead, model simulations predict that NC cell migration requires leading cells to respond to long-range guidance signals and trailing cells to short-range cues in order to maintain a directed, multicellular stream. Experiments confirm differences in leading versus trailing NC cell subpopulations, manifested in unique cell orientation and gene expression patterns that respond to non-linear tissue growth of the migratory domain. Ablation experiments that delete the trailing NC cell subpopulation reveal that leading NC cells distribute all along the migratory pathway and develop a leading/trailing cellular orientation and gene expression profile that is predicted by model simulations. Transplantation experiments and model predictions that move trailing NC cells to the migratory front, or vice versa, reveal that cells adopt a gene expression profile and cell behaviors corresponding to the new position within the migratory stream. These results offer a mechanistic model in which leading cells create and respond to a cell-induced chemotactic gradient and transmit guidance information to trailing cells that use short-range signals to move in a directional manner.
Synthesis and Optical Property Analysis of Novel Anisotropic Light Diffusing Film
Authors: Nishizawa Masahiro , Sekiya Kazuo , Kawakami Toru , Uchida Tatsuo
Published: July 2012

Radical copolymer films with alternating layer structure showed anisotropic diffusion of transmitting light. The haze value of these diffuser films increased according to the amount of initiator. Excessive initiator conditions caused disorder of the layer structure and the disordered light-guide paths would randomize the directions of transmitted light and consequently would enlarge the haze values of the films.
DFT Study on Hydrogen-Bond-Enhanced Aromaticity/Antiaromaticity of the Rings Involved in the π-Conjugated Hydrogen-Bond System: 3-Hydroxy-2H-benzocyclo(propen and penten)-2-ones and 6-Hydroxy-5H-benzocyclohepten-5-one
Authors: Imashiro Fumio
Published: July 2012

In a C=O···HO hydrogen bond incorporated into a π-conjugation system involving ring structures the hydrogen bond decreases the bond alternation of the system and enhances the aromaticity/antiaromaticity of the involved rings depending on the number of π-electrons, influencing stability of the system and barrier to proton transfer along the hydrogen bond.
Synthesis and Properties of Tris-Fused Tetrathiafulvalene Analogues Possessing [3]Dendralene Moieties
Authors: Kajiwara Yoshihiro , Hino Shojun , Misaki Yohji
Published: July 2012

New tris-fused tetrathiafulvalene analogues, in which the outer two TTF units were replaced by [3]dendralenes with triple 1,3-dithiole rings, were synthesized. A theoretical calculation of the unsubstituted derivative based on density functional theory (DFT) using B3LYP/6-31G(d) method suggested that branching 1,3-dithiole rings were almost perpendicular to the central TTF moiety. Cyclic voltammogram of the octakis(methylthio) derivative exhibited five pairs of redox waves at −0.03, 0.06, 0.37, 0.48, and 1.14 V (V vs. Fc/Fc+, in benzonitrile). The first, the second, and the fifth redox processes corresponded to simultaneous two-electron-transfer processes, while the others corresponded to one-electron transfer. The redox behavior and UV–vis–NIR spectra of the octamethyl derivative suggested that the positive charges in the dication and tetracation states distributed mainly on the outer branching vinylogous TTF moieties. A compressed pellet of the charge-transfer complexes of the octamethyl and octakis(methylthio) derivatives with TCNQF4 exhibited moderate conductivity of σrt = 10−3 S cm−1 and semiconductive behavior with activation energies of 0.10–0.13 eV.
High Unemployment Yet Few Small Firms: The Role of Centralized Bargaining in South Africa
Authors: Magruder Jeremy R
Published: July 2012

South Africa has very high unemployment, yet few adults work informally in small firms. This paper tests whether centralized bargaining, by which unionized large firms extend arbitration agreements to nonunionized smaller firms, contributes to this problem. While local labor market characteristics influence the location of these agreements, their coverage is spatially discontinuous, allowing identification by spatial regression discontinuity. Centralized bargaining agreements are found to decrease employment in an industry by 8–13 percent, with losses concentrated among small firms. These effects are not explained by resettlement to uncovered areas, and are robust to a wide variety of controls for unobserved heterogeneity. (JEL J52, K31, L25, O14, O15)
Environmental Noise Impact on School Students' Academic Achievements
Authors: Xie Hui , Kang Jian
Published: July 2012

The aim of this paper is to investigate the relationships between environmental noise levels of schools and a set of academic achievement factors and also, to determine the noise exposure of schools. Secondary schools in Greater London were studied. Four academic achievement indicators were considered and five noise indicators were obtained after processing noise map data. The results show that in the studied schools, the environmental noise levels have almost no significant relationships with those academic achievement indicators. As expected, the secondary schools in Inner London are noisier than those in Outer London, with an average difference of 2dBA.
Reflections on a Novel Coach Education Program: A Narrative Analysis
Authors: Hussain Aman , Trudel Pierre , Patrick Tom , Rossi Anthony
Published: July 2012

This study examines the implementation of Triathlon Canada's novel coach education program within the competition-development context from the perspective of the program designer; the High Performance Director (HPD). An interpretive approach was utilized to create a series of narratives to examine the background, perspectives and approaches used to construct the coach education program. Findings include the unique educational and practical background of the HPD and how it influenced him to design the coach education program the way he did. We also highlight a series of unique innovations for the Triathlon coaches entering the program including, a) submitting a portfolio of prior experiences, b) deemphasizing evaluation and certification and c) the HPD's experiences of getting others to ‘buy’ into the program. We also discuss the various instances of resistance encountered with implementing this type of program and contrast it with other types of conceptualizations of how coaches' learn.
Concepts and Methods for Strategy Building and Tactical Adherence: A Case Study in Football
Authors: Cordes Ole , Lamb Peter F. , Lames Martin
Published: July 2012

This investigation looked at the on-field strategic planning of a professional German soccer club, how the strategic plans were adhered to in competition and how they were adjusted following matches. The methods presented in this article combine qualitative and quantitative techniques and are central to being able to assess objectively strategic plans and playing tactics. The coaching philosophy is a main contributor to the strategic plans, aspects of the match which were directly related to the coaching philosophy were less susceptible to change throughout the season. Additionally, adherence to strategic plans increased as the season progressed and was higher for home matches compared to away. The methods presented in this article have led to a new model of strategic planning, assessment of the quality of strategic plans put in place and the team's adherence to those strategies so that plans for upcoming matches can be optimised. The methods presented and the model for strategic planning and assessment can be used for other sports.
Effects of Actions Preceding the Jump Shot on Gaze Behavior and Shooting Performance in Elite Female Basketball Players
Authors: Oudejans Raôul R. D. , Karamat Rajiv S. , Stolk Maarten H.
Published: July 2012

The aim was to investigate the effects of different actions preceding the jump shot on basketball shooting in expert female basketball players. Participants took two-point jump shots after a dribble or after receiving a pass. The dribble was executed with the dominant or non-dominant hand. Similarly, the pass was received from the side of the dominant or non-dominant hand. Shooting percentages were higher after a pass than after a dribble, and after a dominant-side than after a non-dominant-side pre-action. Higher percentages were accompanied by longer execution times of actions preceding the shot. Furthermore, it appeared that in all conditions players looked at the rim sufficiently long for accurate shooting. We conclude that actions preceding the jump-shot affect shooting percentages. Effects are related to execution time of actions prior to the shot, possibly in combination with the biomechanical consequences of performing these actions on the dominant or non-dominant side.
Effects of an Imagery Workshop on Coaches' Encouragement of Imagery Use
Authors: Edwards Jaymi , Law Barbi , Latimer-Cheung Amy
Published: July 2012

The purpose of this study was to examine whether an imagery workshop would increase recreational level coaches' encouragement of imagery to their athletes when compared to coaches attending a communication workshop. The workshops provided coaches with information, teaching tools, as well as role-playing opportunities. Recreational sport coaches ( n = 132; M age = 41.80 years, SD = 9.67) completed the Coaches Encouragement of Athletes Imagery Use Questionnaire (CEAIUQ)1,Coach-Athlete Relationship Questionnaire (CART-Q)2, and questionnaires assessing coaches' confidence, knowledge, and attitudes towards imagery. Repeated measure MANCOVAs, controlling for sex and highest level coached, revealed no group by time interactions for any of the five functions of imagery. However, group by time interactions were found for knowledge ( F(1, 132) = 5.45, p = .02, ηp2 = .040), attitudes ( F(1,132) = 4.45, p = .01, ηp2 = .055) and confidence ( F(1,132),= 7.10, p = .04, ηp2 = .032) towards imagery. The imagery group significantly increased their confidence from baseline to follow-up (t(65) = −2.75, p = .01). Findings provide direction for designing future coach education training programs and aid in understanding recreational sport coaches' views on encouraging their athletes to use imagery.
The Great Divide: Examining Football Revenue among FBS Schools
Authors: Caro Cary A. , Benton Clayton F.
Published: July 2012

The focus of this study is to examine the dispersion of football-generated revenue amongst Football Bowl Subdivision (FBS) teams. This article seeks to determine if parity exists in the ability of all college football teams to generate revenue, and to determine the impact on the competitive balance of the sport. The results of this study indicate that there is a major stratification among affiliation status (automatic qualifying versus non-automatic qualifying) and within conferences. Further, the data indicates a cycle of inequity in college football. This study quantifies the perception of inequality and recommends means to correct or control this disparity moving forward.
Kinematic Adjustments in the Basketball Free Throw Performed with a Reduced Hoop Diameter Rim
Authors: Khlifa Riadh , Aouadi Ridha , Hermassi Souhail , Chelly Mohamed Souhaiel , Jlid Chedly , Gabbett Tim J.
Published: July 2012

The aim of this study was to investigate the effect of free throw shooting with a reduced diameter rim (diameter 0.35 m) upon the kinematics of basketball free throws. Ten basketball players (mean ± SD age 17.1 ± 0.7 years, height 1.85 ± 0.23 m, body mass 78.8 ± 5.8 kg) performed 8 “clean” successful free throws; 4 in a standard rim (diameter = 0.45 m), and 4 in a reduced diameter rim (diameter = 0.35 m). Ball release angle, ball release speed, ball release height and angles at release in elbow, shoulder, trunk, knee and ankle joints were determined for each subject. Statistical analysis showed significant increases in ball release angle, in ball release speed, in shoulder joint angle at release ( p < 0.0001) and in ball release height ( p < 0.01) when shooting in a reduced diameter rim. There were no other significant differences ( p > 0.05) in any other determined parameter between the standard and reduced rim conditions. The increase of the minimum entry angle of the ball through the rim, caused by the 0.10 m reduction in diameter of the standard rim, resulted in subjects performing clean successful free throws with higher release angles and consequently with higher release speeds. The reduced hoop diameter rim can be used as an aid in training of young basketball players. Specifically, this constraint may act to increase ball release angle in basketball players with low percentage of successful free throws and when the principal cause of decreased free throws accuracy is due to a shot technique with low release angle.
Transport and Deposition of Micro-and Nano-Particles in Human Tracheobronchial Tree by an Asymmetric Multi-Level Bifurcation Model
Authors: Tian Lin , Ahmadi Goodarz
Published: July 2012

Transport and deposition of particles in the upper tracheobronchial tree were analyzed using a multi-level asymmetric lung bifurcation model. The first three generations of tracheobronchial tree were included in the study. The laryngeal jet at the trachea entrance was modeled as an effective turbulence disturbance, and the study was focused on how to accurately simulate the airflow and predict the motion of the inhaled particles. Downstream in the lower level of the bronchial region, a laminar flow model was used, as smoother flow condition was expected. Transport and deposition of nano- and micro-scale spherical particles in the range of 0.01 μm to 30 μm were evaluated. The particle local deposition pattern and deposition rate in the lung bifurcation was discussed. The proposed multi-level asymmetric lung bifurcation model was found to be flexible, easy to use and computationally highly efficient. It was also shown that the selection of the anisotropic Reynolds stress transport turbulence model (RSTM) was appropriate, and the use of the enhanced two-layer model boundary treatment was needed for accurate simulation of the turbulent airflow conditions in the upper airways.