bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining cross-cultural and individual differences in predicting employer reputation as a driver of employer attraction
Authors: Caligiuri Paula , Colakoglu Saba , Cerdin Jean-Luc , Kim Mee Sook
Published: September 2010

This study explores cross-cultural and individual differences in predicting employer reputation as a driver of organizational attraction. Controlling for occupational and generational differences, this study examines the importance of employer reputation when choosing an employer among graduate engineering students in nine countries. At the cultural level, the impact of two cultural syndromes of individualism vs collectivism and verticalness vs horizontalness is examined. At the individual level, the influence of their needs for power and achievement is examined. Results suggest that, at the cultural level, collectivism and, at the individual level, need for power and achievement are related to the importance attached to employer reputation. In practice, companies should consider crafting their recruitment message to fit the cultural norms of the country where they are recruiting and also encourage their recruiting staff members to tailor their messages to fit the candidates they are trying to attract.
Adapted Assessment of Phonological Sensitivity Skills
Authors: Pufpaff Lisa A.
Published: September 2010

Children with little or no functional speech are at risk for literacy acquisition. Assessment of early literacy skills is particularly challenging among this population due to the need for children to provide a spoken response to tasks. This study explored the effects of adapted response modes on measures of phonological sensitivity. Assessment tasks were administered in three response conditions to 12 typically developing kindergarten students with 4 participants in each response condition. Identical tasks were administered in the speech response condition, speech response condition combined with picture response arrays, and nonspeech response condition whereby participants pointed to answers on picture response arrays. Results revealed no statistically significant differences in scores across the three response conditions for 11 of 12 tasks, suggesting that nonspeech assessment of phonological sensitivity should continue to be explored as a feasible option for use among individuals with little or no functional speech.
Psychometric Properties of the Student Risk Screening Scale: An Effective Tool for Use in Diverse Urban Elementary Schools
Authors: Oakes Wendy Peia , Wilder Kaitlin S. , Lane Kathleen Lynne , Powers Lisa , Yokoyama Lynn T. K. , O'Hare Mary Ellen , Jenkins Abbie B.
Published: September 2010

The authors examined the psychometric properties of the Student Risk Screening Scale, as used in three ethnically, culturally, and economically diverse urban midwestern elementary schools. The results suggest strong internal consistency (α = .81—.82) and test-retest stability ( r = .86). Initial ratings of risk as measured by the Student Risk Screening Scale were statistically significant in predicting year-end office discipline referral rates and springtime oral reading fluency scores. Students with higher levels of risk at the onset of the academic year were likely to end the year with moderately higher rates of office discipline referrals and low to moderately lower oral reading fluency proficiency levels. Limitations and future directions are offered.
The Treatment Validity of Autism Screening Instruments
Authors: Livanis Andrew , Mouzakitis Angela
Published: September 2010

Treatment validity is a frequently neglected topic of screening instruments used to identify autism spectrum disorders. Treatment validity, however, should represent an important aspect of these instruments to link the resulting data to the selection of interventions as well as make decisions about treatment length and intensity. Research investigating the treatment validity of screening instruments is an important aspect to explore to assist school-based professionals in treatment planning. The current article reviews the treatment validity of current autism screening instruments and attempts to link their content to the outcomes research in autism in an attempt to identify the most critical items that can inform interventions. A case study is provided at the end of the article to illustrate the process and relationship of universal screening assessment to intervention and progress monitoring.
Around the Fishing Net: Leadership Dynamics for Change in an American International School
Authors: Murakami-Ramalho Elizabeth , Benham Maenette
Published: September 2010

This study explored the active involvement of school and community members investing in leadership dynamics for change, especially considering the increasingly globalized world and the importance of preparing globally minded citizens. To explore how educators and leaders work to foster dynamic learning experiences in a highly mobile global context, we studied leadership dynamics in kindergarten through secondary American international schools’ environments. We inquired, ‘What kinds of leadership dynamics may be found in international schools that further inform the field about generating sustainable environments for teaching and learning?’ One case scenario is presented to illustrate how leadership in times of complexity and change may enhance sustainable environments for teaching and learning at both local and international contexts. The exploration culminated with a deep analysis of leadership dynamics for change, respecting the individual’s participatory power as well as the importance of collective wisdom in action.
Leading to Decide or Deciding to Lead? Understanding the Relationship Between Teacher Leadership and Decision Making
Authors: Emira Mahmoud
Published: September 2010

This article, first, examines how Egyptian teachers and senior teachers (formal leaders) define leadership and whether the length of their teaching experience has an effect on their views. Second, it explores their perspectives on the relationship between teacher leadership and decision making. The research sample is a mixed group of 20 Egyptian teachers of English language, three of them are senior teachers. The length of their teaching experience varies from 2 to 13 years. The findings show that the group defines teacher leadership in terms of characteristics of leaders; styles of leadership and what teacher leaders do both inside and outside classroom. Almost all of them see a link between leadership and decision making. In general, length of experience does not seem to have a major impact on their views. This is a key finding because it raises questions about the Ministry of Education’s (MoE) selection of teachers for leadership responsibilities, which is based on the length of their teaching experience. The implications of these findings are examined in relation to the proposal of the MoE for decentralizing education in Egypt.
Conflicts of Ethos: Issues of Equity and Diversity in Faith-based Schools
Authors: McNamara Gerry , Norman James
Published: September 2010

The recent rise in the number of faith-based schools in Britain creates some interesting issues. On the one hand it is clear that the government, and certainly former Prime Minister Tony Blair, perceives such schools as contributing not only to choice and diversity but also to the raising of educational standards. This appears to be because of an increasingly influential theory that schools with a strong ‘spiritual capital’ (Caldwell, 2008) can raise student achievement. Spiritual capital is defined by Caldwell (2008: 241) as ‘the strength of moral purpose and the degree of coherence among values, beliefs and attitudes about life and learning’. Faith based schools would appear to fit these criteria.
Long-term outcomes of osseointegrated digital prostheses for proximal amputations
Authors: Sierakowski A. , Watts C. , Thomas K. , Elliot D.
Published: September 2010

This paper presents outcomes after 13, 4, and 3½ years in three digital amputees treated with osseointegrated prostheses. One had prosthetic replacement of the index and middle fingers at the PIP level. The second had four fingers replaced at the PIP level, but only three prostheses were retained. The third had a thumb replacement at the MCP level. All patients scored their reconstructed hand highly in terms of appearance and frequency of use. The first and third patients rated the function of the reconstructed hand as similar to the normal hand, and this was confirmed by the Jebsen Test, but the second patient had poor function. All patients could detect pressure and vibration through their prostheses, although grip and pinch strengths were weaker in all three. All three also experienced some pain in the implanted fingers. This study identifies osseointegration as a stable long-term reconstructive option.
BCOR as a novel fusion partner of retinoic acid receptor alpha in a t(X;17)(p11;q12) variant of acute promyelocytic leukemia
Authors: Yamamoto Yukiya , Tsuzuki Sachiko , Tsuzuki Motohiro , Handa Kousuke , Inaguma Yoko , Emi Nobuhiko
Published: September 2010

The majority of acute promyelocytic leukemia (APL) cases are characterized by the presence of a promyelocytic leukemia–retinoic acid receptor alpha(RARA) fusion gene. In a small subset, RARA is fused to a different partner, usually involved in regulating cell growth and differentiation. Here, we identified a novel RARA fusion transcript, BCOR-RARA, in a t(X;17)(p11;q12) variant of APL with unique morphologic features, including rectangular and round cytoplasmic inclusion bodies. Although the patient was clinically responsive to all-trans retinoic acid, several relapses occurred with standard chemotherapy and all-trans retinoic acid. BCOR is a transcriptional corepressor through the proto-oncoprotein, BCL6, recruiting histone deacetylases and polycomb repressive complex 1 components. BCOR-RARA was found to possess common features with other RARA fusion proteins. These included: (1) the same break point in RARA cDNA; (2) self-association; (3) retinoid X receptor alpha is necessary for BCOR-RARA to associate with the RARA responsive element; (4) action in a dominant-negative manner on RARA transcriptional activation; and (5) aberrant subcellular relocalization. It should be noted that there was no intact BCOR found in the 45,-Y,t(X;17)(p11;q12) APL cells because they featured only a rearranged X chromosome. These results highlight essential features of pathogenesis in APL in more detail. BCOR appears to be involved not only in human congenital diseases, but also in a human cancer.
Lineage-instructive function of C/EBPα in multipotent hematopoietic cells and early thymic progenitors
Authors: Wölfler Albert , Danen-van Oorschot Astrid A. , Haanstra Jurgen R. , Valkhof Marijke , Bodner Claudia , Vroegindeweij Eric , van Strien Paulette , Novak Alexandra , Cupedo Tom , Touw Ivo P.
Published: September 2010

Hematopoiesis is tightly controlled by transcription regulatory networks, but how and when specific transcription factors control lineage commitment are still largely unknown. Within the hematopoietic stem cell (Lin−Sca-1+c-Kit+) compartment these lineage-specific transcription factors are expressed at low levels but are up-regulated with the process of lineage specification. CCAAT/enhancer binding protein α (C/EBPα) represents one of these factors and is involved in myeloid development and indispensable for formation of granulocytes. To track the cellular fate of stem and progenitor cells, which express C/EBPα, we developed a mouse model expressing Cre recombinase from the Cebpa promoter and a conditional EYFP allele. We show that Cebpa/EYFP+ cells represent a significant subset of multipotent hematopoietic progenitors, which predominantly give rise to myeloid cells in steady-state hematopoiesis. C/EBPα induced a strong myeloid gene expression signature and down-regulated E2A-induced regulators of early lymphoid development. In addition, Cebpa/EYFP+ cells compose a fraction of early thymic progenitors with robust myeloid potential. However, Cebpa/EYFP+ multipotent hematopoietic progenitors and early thymic progenitors retained the ability to develop into erythroid and T-lymphoid lineages, respectively. These findings support an instructive but argue against a lineage-restrictive role of C/EBPα in multipotent hematopoietic and thymic progenitors.
Efficacy and safety of once-weekly bortezomib in multiple myeloma patients
Authors: Bringhen Sara , Larocca Alessandra , Rossi Davide , Cavalli Maide , Genuardi Mariella , Ria Roberto , Gentili Silvia , Patriarca Francesca , Nozzoli Chiara , Levi Anna , Guglielmelli Tommasina , Benevolo Giulia , Callea Vincenzo , Rizzo Vincenzo , Cangialosi Clotilde , Musto Pellegrino , De Rosa Luca , Liberati Anna Marina , Grasso Mariella , Falcone Antonietta P. , Evangelista Andrea , Cavo Michele , Gaidano Gianluca , Boccadoro Mario , Palumbo Antonio
Published: September 2010

In a recent phase 3 trial, bortezomib-melphalan-prednisone-thalidomide followed by maintenance treatment with bortezomib-thalidomide demonstrated superior efficacy compared with bortezomib-melphalan-prednisone. To decrease neurologic toxicities, the protocol was amended and patients in both arms received once-weekly instead of the initial twice-weekly bortezomib infusions: 372 patients received once-weekly and 139 twice-weekly bortezomib. In this post-hoc analysis we assessed the impact of the schedule change on clinical outcomes and safety. Long-term outcomes appeared similar: 3-year progression-free survival rate was 50% in the once-weekly and 47% in the twice-weekly group (P > .999), and 3-year overall survival rate was 88% and 89%, respectively (P = .54). The complete response rate was 30% in the once-weekly and 35% in the twice-weekly group (P = .27). Nonhematologic grade 3/4 adverse events were reported in 35% of once-weekly patients and 51% of twice-weekly patients (P = .003). The incidence of grade 3/4 peripheral neuropathy was 8% in the once-weekly and 28% in the twice-weekly group (P < .001); 5% of patients in the once-weekly and 15% in the twice-weekly group discontinued therapy because of peripheral neuropathy (P < .001). This improvement in safety did not appear to affect efficacy. This study is registered at http://www.clinicaltrials.gov as NCT01063179.
Isolated splenic metastasis from lung cancer: ringleader of continuous fever
Authors: Tang H. , Huang H. , Xiu Q. , Shi Z.
Published: September 2010

The spleen is an infrequent metastatic organ of solid tumours, the prevalence of which ranges between 2.3% and 7.1% in populations with cancer as determined through autopsy. The most common sources of metastasis are breast, lung, colorectal and ovarian carcinoma and melanoma. Isolated metastasis of the spleen is rarely reported with only 93 cases from all sources having been reported up to 2007. Therefore, isolated splenic metastasis from primary lung cancer is exceedingly rare with only 11 cases reported to date.

Herein, we report a rare case of isolated splenic metastasis in a 49-yr-old female 3 months after lobectomy for an undifferentiated large cell carcinoma in the right lung (pT2aN0M0). The only symptom the patient presented with was continuous high fever, which had never been previously reported. This patient presented diagnostic challenges due to the presentation of high fever, leukoapenia after chemotherapy and the cystic splenic mass, all of which led to the initial consideration of splenic abscess. The patient's high fever resolved rapidly after splenectomy and splenic metastasis was confirmed by pathological findings.

We also reviewed all 11 reported previously cases and summarised the characteristics and appropriate management of isolated splenic metastasis from lung cancer.
Why you do or do not need thoracoscopy
Authors: Janssen J.P.
Published: September 2010

Thoracoscopy is an old but still very valuable technique for the evaluation of pleural pathology and, especially for the further investigation of the aetiology of pleural fluid. It remains of great importance, since it is able to not only provide an exact diagnosis, but also can have therapeutic potential. In this review, the differential diagnostic aspects of transudateversusexudate are further elaborated, and the role of thoracoscopy is compared to closed pleural biopsy and image guided biopsy.
Important role of indels in somatic mutations of human cancer genes
Authors: Yang Haiwang , Zhong Yan , Peng Cheng , Chen Jian-Qun , Tian Dacheng
Published: September 2010

Background

Cancer is clonal proliferation that arises owing to mutations in a subset of genes that confer growth advantage. More and more cancer related genes are found to have accumulated somatic mutations. However, little has been reported about mutational patterns of insertions/deletions (indels) in these genes.

Results

We analyzed indels' abundance and distribution, the relative ratio between indels and somatic base substitutions and the association between those two forms of mutations in a large number of somatic mutations in the Catalogue of Somatic Mutations in Cancer database. We found a strong correlation between indels and base substitutions in cancer-related genes and showed that they tend to concentrate at the same locus in the coding sequences within the same samples. More importantly, a much higher proportion of indels were observed in somatic mutations, as compared to meiotic ones. Furthermore, our analysis demonstrated a great diversity of indels at some loci of cancer-related genes. Particularly in the genes with abundant mutations, the proportion of 3n indels in oncogenes is 7.9 times higher than that in tumor suppressor genes.

Conclusions

There are three distinct patterns of indel distribution in somatic mutations: high proportion, great abundance and non-random distribution. Because of the great influence of indels on gene function (e.g., the effect of frameshift mutation), these patterns indicate that indels are frequently under positive selection and can often be the 'driver mutations' in oncogenesis. Such driver forces can better explain why much less frameshift mutations are in oncogenes while much more in tumor suppressor genes, because of their different function in oncogenesis. These findings contribute to our understanding of mutational patterns and the relationship between indels and cancer.
Prognostic relevance of Bmi-1 expression and autoantibodies in esophageal squamous cell carcinoma
Authors: Liu Wan-li , Guo Xian-zhi , Zhang Lan-jun , Wang Jun-ye , Zhang Ge , Guan Su , Chen Yu-min , Kong Qing-li , Xu Li-hua , Li Man-zhi , Song Li-bing , Zeng Mu-sheng
Published: September 2010

Background

Overexpression of Bmi-1 has been observed in a variety of cancers, and it has been suggested to be an independent prognostic marker for the patients. The objective of this study was to determine the level of Bmi-1 expression or its autoantibodies in human esophageal squamous cell carcinoma (ESCC) and to correlate it with clinicopathologic data.

Methods

We first examined Bmi-1 expression in ESCC cell lines and tumor samples by RT-PCR and Western blot analysis. We then analyzed Bmi-1 protein expression in 171 clinicopathologically characterized ESCC cases by immunohistochemistry. In addition, we detected its autoantibodies in sera of patients with ESCC by ELISA.

Results

We found that Bmi-1 expression was higher in the immortalized cells, cancer cell lines and most cancer tissue than in non-tumorous control tissue at both mRNA and protein level. In addition, Bmi-1 expression was observed in 64.3% (110 of 171) archive ESCC specimen by immunohistochemistry analysis, and the location of Bmi-1 in ESCC was in the nuclei instead of cytoplasm of tumor cells. There was a significant difference of Bmi-1 expression in patients categorized according to stage (P = 0.003) and pN classification (P = 0.047). Multivariate analysis suggested that Bmi-1 expression was an independent prognostic marker for ESCC patients. A prognostic significance of Bmi-1 was also found in the subgroup of T3~T4 and N1 tumor classification. Bmi-1 autoantibodies were detected in sera of 39.0% (62 of 159) ESCC patients. The correlations between anti-Bmi-1 antibodies and tumor stage (P = 0.040), or lymph node status (P < 0.001) were significant.

Conclusions

Our results suggest that Bmi-1 protein is a valuable marker of ESCC progression. The presence of Bmi-1 autoantibodies in sera from patients with ESCC may have clinical utility in esophageal cancer diagnosis.
Social structural factors that shape assisted injecting practices among injection drug users in Vancouver, Canada: a qualitative study
Authors: Fairbairn Nadia , Small Will , Van Borek Natasha , Wood Evan , Kerr Thomas
Published: September 2010

Background

Injection drug users (IDU) commonly seek manual assistance with illicit drug injections, a practice known to be associated with various health-related harms. We investigated the social structural factors that shape risks related to assisted injection and the harms that may result.

Methods

Twenty semi-structured qualitative interviews were conducted with IDU enrolled in the ACCESS or Vancouver Injection Drug Users Study (VIDUS) who reported requiring assistance injecting in the past six months. Audio-recorded interviews were transcribed verbatim and a thematic analysis was conducted.

Results

Barriers to self-injecting included a lack of knowledge of proper injecting technique, a loss of accessible veins, and drug withdrawal. The exchange of money or drugs for assistance with injecting was common. Harms experienced by IDU requiring assistance injecting included theft of the drug, missed injections, overdose, and risk of blood-borne disease transmission. Increased vulnerability to HIV/HCV infection within the context of intimate relationships was represented in participant narratives. IDU identified a lack of services available for those who require assistance injecting, with notable mention of restricted use of Vancouver's supervised injection facility.

Conclusions

This study documents numerous severe harms that arise from assisted injecting. Social structural factors that shape the risks related to assisted injection in the Vancouver context included intimate partner relations and social conventions requiring an exchange of goods for provision of injecting assistance. Health services for IDU who need help injecting should include targeted interventions, and supervised injection facilities should attempt to accommodate individuals who require assistance with injecting.
Can bone loss be reversed by antithyroid drug therapy in premenopausal women with Graves' disease?
Authors: Belsing Tina Z , Tofteng Charlotte , Langdahl Bente L , Charles Peder , Feldt-Rasmussen Ulla
Published: September 2010

Context

Hyperthyroidism can lead to reduced bone mineral density (BMD) and increased fracture risk particularly in postmenopausal women, but the mechanism behind is still unclear.

Objective

Prospective examination of the influence of thyroid hormones and/or thyroid autoantibodies on BMD in premenopause.

Design

We have examined 32 premenopausal women with untreated active Graves' disease from time of diagnosis, during 18 months of antithyroid drug therapy (ATD) and additionally 18 months after discontinuing ATD. Variables of thyroid metabolism, calcium homeostasis and body composition were measured every 3 months. BMD of lumbar spine and femoral neck were measured at baseline, 18 ± 3 and 36 ± 3 months. Data were compared to base line, a sex- and age matched control group and a group of patients with Hashimoto's thyroiditis treated with non-suppressive doses of levothyroxine.

Results

The study showed significantly (p < 0.002) lower BMD in the thyrotoxic state compared to the control group with subsequent significant improvement during 18 ± 3 months of ATD compared to baseline (p < 0.001). However, during the following 18 months after stopping ATD femoral neck BMD decreased again unrelated to age (more than 0.4% per year, p < 0,002). The wellestablished effect of thyrotoxicosis on calcium homeostasis was confirmed. The positive predictor for best BMD was TSH receptor antibodies (TRAb) while free T4 correlated negatively in the thyrotoxic female Graves' patients (p < 0.02 and p < 0.003). In healthy controls and patients with treated Graves' disease both TSH and T4 correlated negatively to the bone mass (BMC) (p < 0.003).

Conclusion

The results indicated a clinically relevant impact of thyroid function on bone modulation also in premenopausal women with Graves' disease, and further indicated the possibility for a direct action of TRAb on bones.
Migration, early axonogenesis, and Reelin-dependent layer-forming behavior of early/posterior-born Purkinje cells in the developing mouse lateral cerebellum
Authors: Miyata Takaki , Ono Yuichi , Okamoto Mayumi , Masaoka Makoto , Sakakibara Akira , Kawaguchi Ayano , Hashimoto Mitsuhiro , Ogawa Masaharu
Published: September 2010

Background

Cerebellar corticogenesis begins with the assembly of Purkinje cells into the Purkinje plate (PP) by embryonic day 14.5 (E14.5) in mice. Although the dependence of PP formation on the secreted protein Reelin is well known and a prevailing model suggests that Purkinje cells migrate along the 'radial glial' fibers connecting the ventricular and pial surfaces, it is not clear how Purkinje cells behave in response to Reelin to initiate the PP. Furthermore, it is not known what nascent Purkinje cells look like in vivo. When and how Purkinje cells start axonogenesis must also be elucidated.

Results

We show that Purkinje cells generated on E10.5 in the posterior periventricular region of the lateral cerebellum migrate tangentially, after only transiently migrating radially, towards the anterior, exhibiting an elongated morphology consistent with axonogenesis at E12.5. After their somata reach the outer/dorsal region by E13.5, they change 'posture' by E14.5 through remodeling of non-axon (dendrite-like) processes and a switchback-like mode of somal movement towards a superficial Reelin-rich zone, while their axon-like fibers remain relatively deep, which demarcates the somata-packed portion as a plate. In reeler cerebella, the early born posterior lateral Purkinje cells are initially normal during migration with anteriorly extended axon-like fibers until E13.5, but then fail to form the PP due to lack of the posture-change step.

Conclusions

Previously unknown behaviors are revealed for a subset of Purkinje cells born early in the posteior lateral cerebellum: tangential migration; early axonogenesis; and Reelin-dependent reorientation initiating PP formation. This study provides a solid basis for further elucidation of Reelin's function and the mechanisms underlying the cerebellar corticogenesis, and will contribute to the understanding of how polarization of individual cells drives overall brain morphogenesis.
Enrichment and differential targeting of complexins 3 and 4 in ribbon-containing sensory neurons during zebrafish development
Authors: Zanazzi George , Matthews Gary
Published: September 2010

Background

In sensory systems with broad bandwidths, polarized receptor cells utilize highly specialized organelles in their apical and basolateral compartments to transduce and ultimately transmit signals to the rest of the nervous system. While progress has been made in elucidating the assembly of the transduction apparatus, the development of synaptic ribbon-containing terminals remains poorly understood. To begin to delineate the targeting of the exocytotic machinery specifically in ribbon-containing neurons, we have examined the expression of complexins 3 and 4 in the zebrafish visual and acousticolateral systems during the first week of development.

Results

We have identified five members of the complexin 3/4 subfamily in zebrafish that show 50 to 75% amino acid identity with mammalian complexins 3 and 4. Utilizing a polyclonal antibody that recognizes all five orthologs, we demonstrate that these proteins are enriched in ribbon-containing sensory neurons. Complexin 3/4 is rapidly targeted to presynaptic terminals in the pineal organ and retina concomitantly with RIBEYE b, a component of ribbons. In hair cells of the inner ear and lateral line, however, complexin 3/4 immunoreactivity clusters on the apical surfaces of hair cells, among their stereocilia, rather than along the basolateral plasma membrane with RIBEYE b. A complexin 4a-specific antibody selectively labels the presynaptic terminals of visual system ribbon-containing neurons.

Conclusions

These results provide evidence for the concurrent transport and/or assembly of multiple components of the active zone in developing ribbon terminals. Members of the complexin 3/4 subfamily are enriched in these terminals in the visual system and in hair bundles of the acousticolateral system, suggesting that these proteins are differentially targeted and may have multiple roles in ribbon-containing sensory neurons.
Mast cells and hypoxia drive tissue metaplasia and heterotopic ossification in idiopathic arthrofibrosis after total knee arthroplasty
Authors: Freeman Theresa A , Parvizi Javad , Dela Valle Craig J , Steinbeck Marla J
Published: September 2010

Background

Idiopathic arthrofibrosis occurs in 3-4% of patients who undergo total knee arthroplasty (TKA). However, little is known about the cellular or molecular changes involved in the onset or progression of this condition. To classify the histomorphologic changes and evaluate potential contributing factors, periarticular tissues from the knees of patients with arthrofibrosis were analyzed for fibroblast and mast cell proliferation, heterotopic ossification, cellular apoptosis, hypoxia and oxidative stress.

Results

The arthrofibrotic tissue was composed of dense fibroblastic regions, with limited vascularity along the outer edges. Within the fibrotic regions, elevated numbers of chymase/fibroblast growth factor (FGF)-expressing mast cells were observed. In addition, this region contained fibrocartilage and associated heterotopic ossification, which quantitatively correlated with decreased range of motion (stiffness). Fibrotic, fibrocartilage and ossified regions contained few terminal dUTP nick end labeling (TUNEL)-positive or apoptotic cells, despite positive immunostaining for lactate dehydrogenase (LDH)5, a marker of hypoxia, and nitrotyrosine, a marker for protein nitrosylation. LDH5 and nitrotyrosine were found in the same tissue areas, indicating that hypoxic areas within the tissue were associated with increased production of reactive oxygen and nitrogen species.

Conclusions

Taken together, we suggest that hypoxia-associated oxidative stress initiates mast cell proliferation and FGF secretion, spurring fibroblast proliferation and tissue fibrosis. Fibroblasts within this hypoxic environment undergo metaplastic transformation to fibrocartilage, followed by heterotopic ossification, resulting in increased joint stiffness. Thus, hypoxia and associated oxidative stress are potential therapeutic targets for fibrosis and metaplastic progression of idiopathic arthrofibrosis after TKA.
Expression of transcription factors snail, slug, and twist in human bladder carcinoma
Authors: Yu Qinchao , Zhang Kejun , Wang Xinsheng , Liu Xiangping , Zhang Zemi
Published: September 2010

Background

Slug, Snail, and Twist are transcription factors that regulate the expression of tumor suppressors such as E-cadherin. In this study, we aimed to examine the expression of these transcription factors in human bladder carcinoma.

Methods

We first investigated expression of Slug, Snail, Twist and E-cadherin in five bladder Carcinoma cell lines by reverse transcription-polymerase chain reaction and western blotting. Furthermore, we investigated Slug, Snail, and Twist and E-cadherin expression by immunohistochemistry with bladder carcinoma (tumor, n = 120; background, n = 42).

Results

Expression of Slug mRNA and protein was detected in all cell lines, Twist was clearly expressed in two out of five bladder carcinoma cell lines, Snail was not expressed, and E-cadherin was detected in 3 cell lines. 44.2% (53/120) of human bladder Carcinoma tissues and 38%(16/42) background tissue showed an expression of Twist; 62.5%(75/120) of human bladder Carcinoma tissues and 40%(17/42) background tissue showed an expression of Slug, 15.8% (19/120) of human bladder Carcinoma tissues and 76%(32/42) background tissue showed an expression of Snail, and 25.8% (31/120) cases were negative for E-cadherin expression in carcinoma tissues. Expression of Slug and Twist shows increased levels in tumors, whereas Snail seems reduced. Statistically significant correlations were found between Twist, Slug, and E-cadherin expression. Immunohistochemistry analysis showed that Twist was elevated with increasing tumor stage (P= 0.001), the grade (P< 0.001), the progression (P= 0.035). Slug was elevated and Snail was reduced with increasing nodal involvement (tumor-node-metastasis status) (P= 0.004,P= 0.01). E-cadherin was reduced in expression corresponding with tumor grade (P< 0.01). Positive Twist, Slug and E-cadherin expression clearly predicted poorer PFS (P= 0.042,P= 0.014,P= 0.001). In the multivariate analysis, only Snail and E-cadherin expression were independent prognostic factors for OS (P = 0.002,P< 0.001).

Conclusions

These data demonstrate that Twist, Snail and Slug have inappropriate expression in bladder carcinoma and that this may play a part in the progression of human bladder carcinoma.
Effectiveness of dry needling and injections of myofascial trigger points associated with plantar heel pain: a systematic review
Authors: Cotchett Matthew P , Landorf Karl B , Munteanu Shannon E
Published: September 2010

Background

Plantar heel pain (plantar fasciitis) is one of the most common musculoskeletal pathologies of the foot. Plantar heel pain can be managed with dry needling and/or injection of myofascial trigger points (MTrPs) however the evidence for its effectiveness is uncertain. Therefore, we aimed to systematically review the current evidence for the effectiveness of dry needling and/or injections of MTrPs associated with plantar heel pain.

Methods

We searched specific electronic databases (MEDLINE, EMBASE, AMED, CINAHL, SPORTDiscus and AMI) in April 2010 to identify randomised and non‐randomised trials. We included trials where participants diagnosed with plantar heel pain were treated with dry needling and/or injections (local anaesthetics, steroids, Botulinum toxin A and saline) alone or in combination with acupuncture. Outcome measures that focussed on pain and function were extracted from the data. Trials were assessed for quality using the Quality Index tool.

Results

Three quasi‐experimental trials matched the inclusion criteria: two trials found a reduction in pain for the use of trigger point dry needling when combined with acupuncture and the third found a reduction in pain using 1% lidocaine injections when combined with physical therapy. However, the methodological quality of the three trials was poor, with Quality Index scores ranging form 7 to 12 out of a possible score of 27. A meta‐analysis was not conducted because substantial heterogeneity was present between trials.

Conclusions

There is limited evidence for the effectiveness of dry needling and/or injections of MTrPs associated with plantar heel pain. However, the poor quality and heterogeneous nature of the included studies precludes definitive conclusions being made. Importantly, this review highlights the need for future trials to use rigorous randomised controlled methodology with measures such as blinding to reduce bias. We also recommend that such trials adhere to the Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA) to ensure transparency.
Connecting Biology and Mathematics: First Prepare the Teachers
Authors: Šorgo Andrej
Published: September 2010

Developing the connection between biology and mathematics is one of the most important ways to shift the paradigms of both established science disciplines. However, adding some mathematic content to biology or biology content to mathematics is not enough but must be accompanied by development of suitable pedagogical models. I propose a model of pedagogical mathematical biological content knowledge as a feasible starting point for connecting biology and mathematics in schools and universities. The process of connecting these disciplines should start as early as possible in the educational process, in order to produce prepared minds that will be able to combine both disciplines at graduate and postgraduate levels of study. Because teachers are a crucial factor in introducing innovations in education, the first step toward such a goal should be the education of prospective and practicing elementary and secondary school teachers.
Mathematical Biology Modules Based on Modern Molecular Biology and Modern Discrete Mathematics
Authors: Robeva Raina , Davies Robin , Hodge Terrell , Enyedi Alexander
Published: September 2010

We describe an ongoing collaborative curriculum materials development project between Sweet Briar College and Western Michigan University, with support from the National Science Foundation. We present a collection of modules under development that can be used in existing mathematics and biology courses, and we address a critical national need to introduce students to mathematical methods beyond the interface of biology with calculus. Based on ongoing research, and designed to use the project-based-learning approach, the modules highlight applications of modern discrete mathematics and algebraic statistics to pressing problems in molecular biology. For the majority of projects, calculus is not a required prerequisite and, due to the modest amount of mathematical background needed for some of the modules, the materials can be used for an early introduction to mathematical modeling. At the same time, most modules are connected with topics in linear and abstract algebra, algebraic geometry, and probability, and they can be used as meaningful applied introductions into the relevant advanced-level mathematics courses. Open-source software is used to facilitate the relevant computations. As a detailed example, we outline a module that focuses on Boolean models of the lac operon network.
From Biology to Mathematical Models and Back: Teaching Modeling to Biology Students, and Biology to Math and Engineering Students
Authors: Chiel Hillel J. , McManus Jeffrey M. , Shaw Kendrick M.
Published: September 2010

We describe the development of a course to teach modeling and mathematical analysis skills to students of biology and to teach biology to students with strong backgrounds in mathematics, physics, or engineering. The two groups of students have different ways of learning material and often have strong negative feelings toward the area of knowledge that they find difficult. To give students a sense of mastery in each area, several complementary approaches are used in the course: 1) a “live” textbook that allows students to explore models and mathematical processes interactively; 2) benchmark problems providing key skills on which students make continuous progress; 3) assignment of students to teams of two throughout the semester; 4) regular one-on-one interactions with instructors throughout the semester; and 5) a term project in which students reconstruct, analyze, extend, and then write in detail about a recently published biological model. Based on student evaluations and comments, an attitude survey, and the quality of the students' term papers, the course has significantly increased the ability and willingness of biology students to use mathematical concepts and modeling tools to understand biological systems, and it has significantly enhanced engineering students' appreciation of biology.
RNA Secondary Structure Prediction by Using Discrete Mathematics: An Interdisciplinary Research Experience for Undergraduate Students
Authors: Ellington Roni , Wachira James , Nkwanta Asamoah
Published: September 2010

The focus of this Research Experience for Undergraduates (REU) project was on RNA secondary structure prediction by using a lattice walk approach. The lattice walk approach is a combinatorial and computational biology method used to enumerate possible secondary structures and predict RNA secondary structure from RNA sequences. The method uses discrete mathematical techniques and identifies specified base pairs as parameters. The goal of the REU was to introduce upper-level undergraduate students to the principles and challenges of interdisciplinary research in molecular biology and discrete mathematics. At the beginning of the project, students from the biology and mathematics departments of a mid-sized university received instruction on the role of secondary structure in the function of eukaryotic RNAs and RNA viruses, RNA related to combinatorics, and the National Center for Biotechnology Information resources. The student research projects focused on RNA secondary structure prediction on a regulatory region of the yellow fever virus RNA genome and on an untranslated region of an mRNA of a gene associated with the neurological disorder epilepsy. At the end of the project, the REU students gave poster and oral presentations, and they submitted written final project reports to the program director. The outcome of the REU was that the students gained transferable knowledge and skills in bioinformatics and an awareness of the applications of discrete mathematics to biological research problems.
Endogenous PGE2 promotes the induction of human Th17 responses by fungal β-glucan
Authors: Gagliardi Maria Cristina , Teloni Raffaela , Mariotti Sabrina , Bromuro Carla , Chiani Paola , Romagnoli Giulia , Giannoni Federico , Torosantucci Antonella , Nisini Roberto
Published: September 2010

C. albicans β-glucan induces PGE2 production by human DC and promotes Th17 cell expansion.

The interaction of PAMPs with cells of the innate immune system shapes the adaptive host response. Here, we report that β-glucan, a major fungal PAMP purified from Candida albicans, stimulates human DCs to secrete a pro-Th17 cytokine pattern. Notably, β-glucan induces PGE2 production, which has been shown to play a pivotal role in Th17 cell expansion. Inhibition of PGE2 synthesis or blockade of PGE2 receptors EP2 and EP4 drastically reduces IL-23 production by β-glucan-activated DCs, suggesting that endogenous PGE2 amplifies IL-23 synthesis in response to the C. albicans PAMP. Moreover β-glucan promotes the expansion of Th17 cells, which is strongly decreased by EP2 and EP4 receptor blockade on DCs. Our results highlight a novel role for PGE2 in the regulation of innate and adaptive immune response triggered by recognition of a prominent, highly conserved fungal PAMP such as β-glucan.
Arsenic modulates APOBEC3G-mediated restriction to HIV-1 infection in myeloid dendritic cells
Authors: Stalder Romaine , Blanchet Fabien , Mangeat Bastien , Piguet Vincent
Published: September 2010

An APOBEC3G-dependent restriction operates in blood-derived myeloid dendritic cells, which can be relieved by arsenic trioxide.

DC are major targets of HIV-1 during the early events of infection. Yet, HIV-1 infects these cells only inefficiently in vitro as compared with CD4+T lymphocytes. Accordingly, we have previously identified a strong post-entry block to HIV-1 replication in MDDC as a result of the cellular restriction factor A3G. Furthermore, we have demonstrated that As2O3, a drug used to treat acute promyelocytic leukemia, can fully eliminate the potent post-entry restriction of HIV-1 infection in MDDC and in blood-derived MyDC by mechanisms that were unclear. We are now exploring the interplay between As2O3 and A3G-mediated restriction in primary DC subsets. Here, we report that As2O3 counteracts A3G-mediated restriction in MyDC but not in MDDC. RNAi of A3G in MyDC indicated that the As2O3-mediated increase of HIV-1 infection was largely dependent on the presence of the cellular restriction factor. This study reveals an unexpected interplay between As2O3 and A3G-mediated restriction to HIV-1 infection in primary human MyDC.
T-bet-independent effects of IL-12 family cytokines on regulation of Th17 responses to experimental T. cruzi infection
Authors: Cobb Dustin , Hambright Derek , Smeltz Ronald B
Published: September 2010

IFN-γ is not required for T-bet-dependent inhibition of Th17 responses to T. cruzi infection, but can synergize with IL-12 to reduce T. cruzi-specific IL-17 production.

Tbx21 (i.e., T-bet) is an IFN-γ-inducible transcription factor that promotes Th1 differentiation. Previously, we reported that Tbx21−/− mice develop a robust Th17 response to the parasite Trypanosoma cruzi, including CD4+ T cell subsets producing IL-17 and IFN-γ. Because of the known inhibitory effects of IFN-γ on Th17 cells, the purpose of this study was to determine the contribution of IFN-γ to regulation of Th17 differentiation during the course of T. cruzi infection. We observed that infection of IFN-γ−/− or Stat-1−/− mice generated increased numbers of IL-17-producing cells. In sharp contrast to infected Stat-1−/− or Tbx21−/− mice, however, IFN-γ−/− mice developed a lower overall Th17 response, suggesting that IFN-γ was not required for T-bet-dependent activity, including T-bet-dependent expression of CXCR3. To determine if IFN-γ could influence Th17 responses indirectly by acting on APCs, we neutralized IFN-γ in cultures containing APC and T. cruzi antigens. Although anti-IFN-γ increased IL-17 production modestly, anti-IFN-γ and anti-IL-12 led to a significant enhancement of T. cruzi-specific IL-17 (P<0.01). In contrast to the inhibitory effects of IL-12, IL-23 was able to stimulate Tbx21−/− T cells and cause a striking increase in T. cruzi-specific IL-17. These data show that the IL-12 family of cytokines can influence Th17 responses in a T-bet-independent manner and that the effects of IFN-γ are not necessarily related to its ability to induce T-bet expression in T cells.
Protective effects of apocynin, an inhibitor of NADPH oxidase activity, in splanchnic artery occlusion and reperfusion
Authors: Paterniti Irene , Galuppo Maria , Mazzon Emanuela , Impellizzeri Daniela , Esposito Emanuela , Bramanti Placido , Cuzzocrea Salvatore
Published: September 2010

Pharmacological action of Apocynin, used as an inhibitor of NADPH-oxidase, when applied to an experimental model of SAO shock.

SAO shock is a severe form of circulatory shock produced by I/R of the splanchnic organs. SAO causes an enhanced formation of ROS, which contributes to the pathophysiology of shock. Apocynin is a naturally occurring, methoxy-substituted catechol, experimentally used as an inhibitor of NOX. It can decrease the production of ROS from activated neutrophils and macrophages, inhibiting the assembly of NADPH-oxidase activity. In this study, we wanted to evaluate the pharmacological action of apocynin in rats subjected to SAO shock, which was induced by clamping the superior mesenteric artery and the celiac trunk, resulting in a total occlusion of these arteries for 45 min. After this period of occlusion, the clamps were removed. Administration of apocynin i.p. (5 mg/kg i.p. 10% DMSO) 5 min before reperfusion significantly reduced the (1) histological evidence of tissue injury, (2) proinflammatory cytokine production (TNF-α, IL-1β), (3) adhesion molecules (ICAM-1, P-selectin), (4) nitrotyrosine formation, (5) NF-κB expression, and (6) apoptosis (Bax, Bcl-2, Fas-L, and TUNEL). These results could imply a future use of apocynin in the treatment of I/R shock.