bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measuring functional connectivity using long‐term monitoring data
Authors: Powney Gary D. , Roy David B. , Chapman Daniel , Brereton Tom , Oliver Tom H. 
Published: March 2011

Summary1. We use population synchrony as a new empirical method to assess functional connectivity – the permeability of landscapes given species dispersal attributes. Functional connectivity is important because well‐connected metapopulations are expected to be more resistant to stochastic events causing extinction.2. A variety of factors impact population synchrony, and we attempt to account for several of these (shared climate, distance, habitat similarity and location within the range) before investigating impacts of the suitability of the landscape between populations – a proxy for permeability to dispersal.3. For the Speckled Wood butterfly (Pararge aegeria), we find that population synchrony is positively correlated with landscape suitability, suggesting that synchrony might be used to measure functional connectivity.4. The importance of landscape suitability for population synchrony shows a humped relationship with distance – suitability has no effect between 0 and 20 km, then showing a significant positive effect above 20 km but with reduced (still significant) effect from 160 to 200 km. This suggests that relatively close populations may exchange sufficient migrants for synchronisation, regardless of the matrix suitability. In contrast, more separate populations are synchronised only where the landscape permits functional connectivity, most likely through dispersal between intermediate stepping‐stone populations.5.Synthesis and applications. We show that patterns of synchrony in long‐term monitoring data can be used to estimate functional connectivity of landscapes. As such, this technique might be used to test and prioritise the effectiveness of land management for conservation of species and to mitigate the effects of climate change.
Teacher beliefs, teacher characteristics, and school contextual factors: What are the relationships?
Authors: Rubie‐Davies Christine M. , Flint Annaline , McDonald Lyn G. 
Published: March 2011

Background. There is a plethora of research around student beliefs and their contribution to student outcomes. However, there is less research in relation to teacher beliefs. Teacher factors are important to consider since beliefs mould thoughts and resultant instructional behaviours that, in turn, can contribute to student outcomes.Aims. The purpose of this research was to explore relationships between the teacher characteristics of gender and teaching experience, school contextual variables (socio‐economic level of school and class level), and three teacher socio‐psychological variables: class level teacher expectations, teacher efficacy, and teacher goal orientation.Sample. The participants were 68 male and female teachers with varying experience, from schools in a variety of socio‐economic areas and from rural and urban locations within New Zealand.Method. Teachers completed a questionnaire containing items related to teacher efficacy and goal orientation in reading. They also completed a teacher expectation survey. Reading achievement data were collected on students. Interrelationships were explored between teacher socio‐psychological beliefs and the teacher and school factors included in the study.Results. Mastery‐oriented beliefs predicted teacher efficacy for student engagement and classroom management. The socio‐economic level of the school and teacher gender predicted teacher efficacy for engagement, classroom management, instructional strategies, and a mastery goal orientation. Being male predicted a performance goal orientation.Conclusions. Teacher beliefs, teacher characteristics, and school contextual variables can result in differences in teacher instructional practices and differing classroom climates. Further investigation of these variables is important since differences in teachers contribute to differences in student outcomes.
The Neutralization Breadth of HIV-1 Develops Incrementally over Four Years and Is Associated with CD4
+
T Cell Decline and High Viral Load during Acute Infection
Authors: Gray Elin S. , Madiga Maphuti C. , Hermanus Tandile , Moore Penny L. , Wibmer Constantinos Kurt , Tumba Nancy L. , Werner Lise , Mlisana Koleka , Sibeko Sengeziwe , Williamson Carolyn , Abdool Karim Salim S. , Morris Lynn ,   and the CAPRISA002 Study Team
Published: March 2011

ABSTRACT

An understanding of how broadly neutralizing activity develops in HIV-1-infected individuals is needed to guide vaccine design and immunization strategies. Here we used a large panel of 44 HIV-1 envelope variants (subtypes A, B, and C) to evaluate the presence of broadly neutralizing antibodies in serum samples obtained 3 years after seroconversion from 40 women enrolled in the CAPRISA 002 acute infection cohort. Seven of 40 participants had serum antibodies that neutralized more than 40% of viruses tested and were considered to have neutralization breadth. Among the samples with breadth, CAP257 serum neutralized 82% (36/44 variants) of the panel, while CAP256 serum neutralized 77% (33/43 variants) of the panel. Analysis of longitudinal samples showed that breadth developed gradually starting from year 2, with the number of viruses neutralized as well as the antibody titer increasing over time. Interestingly, neutralization breadth peaked at 4 years postinfection, with no increase thereafter. The extent of cross-neutralizing activity correlated with CD4
+
T cell decline, viral load, and CD4
+
T cell count at 6 months postinfection but not at later time points, suggesting that early events set the stage for the development of breadth. However, in a multivariate analysis, CD4 decline was the major driver of this association, as viral load was not an independent predictor of breadth. Mapping of the epitopes targeted by cross-neutralizing antibodies revealed that in one individual these antibodies recognized the membrane-proximal external region (MPER), while in two other individuals, cross-neutralizing activity was adsorbed by monomeric gp120 and targeted epitopes that involved the N-linked glycan at position 332 in the C3 region. Serum antibodies from the other four participants targeted quaternary epitopes, at least 2 of which were PG9/16-like and depended on the N160 and/or L165 residue in the V2 region. These data indicate that fewer than 20% of HIV-1 subtype C-infected individuals develop antibodies with cross-neutralizing activity after 3 years of infection and that these antibodies target different regions of the HIV-1 envelope, including as yet uncharacterized epitopes.
The attitudes of relatives to autopsy: a misconception
Authors: Tsitsikas Dimitris A , Brothwell Morag , Chin Aleong Jo-Anne , Lister Andrew T 
Published: March 2011

AimHospital autopsy rates have been falling steadily over recent decades. One factor that has been implicated in this decline is the perception that the general public views postmortem examinations unfavourably and that this often makes clinicians reluctant to discuss autopsy with families and seek their consent. The aim of this study was to test this assumption.Objectives/methodsIn the division of lymphoid malignancies at St Bartholomew's Hospital, we suggested autopsy and discussed it in depth with the families of all the patients who died in hospital in an 8-month period in order to assess whether the autopsy rate could be increased by improving the approach to the relatives.ResultsConsent for a postmortem examination was requested in 18 of 23 cases and granted in 16 cases, giving a consent rate of 89%, and an overall rate of autopsy of 69.5%.ConclusionThe attitude of the general public is positive overall, and translates into high autopsy rates when the value of the examination is presented honestly and the details of the procedure are adequately explained.
Granulomatous mastitis: the histological differentials
Authors: Lacambra Maribel , Thai Tu Anh , Lam Christopher C F , Yu Alex M C , Pham Huong Thien , Tran Phuong Viet The , Law Bonita K B , Van Nguyen Thanh , Pham Dung Xuan , Tse Gary M 
Published: March 2011

BackgroundThe management of granulomatous mastitis depends on the causative factor, and accurate diagnosis in distinguishing between idiopathic granulomatous mastitis (IGM) and tuberculous mastitis (TBM) is indispensable. This is particularly problematic in the cases of granulomatous mastitis in which the microbiological studies are negative. In this study, in a large cohort, the histological features for IGM and TBM were compared.MethodsThe histopathology files from the two participating hospitals were searched for cases of granulomatous inflammation of the breast over an 8-year period. The parameters assessed included age of patient, lesional size, systemic and local symptoms, and histological findings of inflammatory cells, granulomas, necrosis, multinucleated giant cells, fibrosis and calcifications.Results29 cases of IGM and 33 cases of TBM were included in this study. A significant difference was seen between the two groups with regard to patient age (t=2.52, p<0.05) and lesional size (t=−5.56, p<0.01). TBM occurred in a significantly younger population, and demonstrated larger lesional sizes than IGM. There was no difference between the number of cases showing mass, local and systemic symptoms. Comparing the different histological features, the TBM group showed significantly more fibrosis, eosinophils and necrosis, whereas the IGM group showed significantly more plasma cells. Taking all the cases together as one group to evaluate the relationship between the histological parameters, there was significant positive correlation between eosinophils and fibrosis (rs=0.39, p<0.01), and negative correlation between vague and well-formed granulomas (rs=−0.38, p<0.01).ConclusionTBM was more likely to occur in younger patients, with a larger clinical mass at presentation. Histologically, TBM tends to show more eosinophils and necrosis, and IGM is associated with more plasma cells. The characteristics of the granulomas and giant cells were not distinguishing features.
Microbiological findings in sudden unexpected death in infancy: comparison of immediate postmortem sampling in casualty departments and at autopsy
Authors: Pryce Jeremy W , Roberts Sebastian E A , Weber Martin A , Klein Nigel J , Ashworth Michael T , Sebire Neil J 
Published: March 2011

AimSudden unexpected death in infancy (SUDI) represents the commonest presentation of post-neonatal infant death in the UK. This audit reviews current practice in the investigation of SUDI deaths, with particular regard to the practice of microbiological sampling in emergency departments (ED) compared with samples obtained at the time of autopsy for establishing the cause of death, as suggested by current guidelines.MethodsCoronial autopsies performed for the indication of SUDI over a 4-year period at a single specialist centre were reviewed with particular regard to the findings of microbiological investigations performed in ED compared with those performed at the time of autopsy.ResultsOf 229 SUDI postmortems performed during the period, there were 136 cases in which both bacteriological samples taken in ED and at autopsy were available, including 109 with blood cultures taken at both time points. 66 cases had sterile blood cultures in ED of which 37 (56%) showed positive microbiological growth from autopsy samples including nine (14%) cases with group II pathogens. Group II pathogens were identified from ED samples in six (6%) of the total cases; all but two cases ofStaphylococcus aureuswere not detected at autopsy.ConclusionBlood cultures obtained at autopsy are associated with a significantly higher rate of positive microbial cultures compared with blood samples taken in life. Most represent easily identified postmortem translocation or overgrowth rather than infection as the cause of death. No cases with a final infective cause of death would have been missed if ED sampling had not been performed.
Heavy Chain Ferritin siRNA Delivered by Cationic Liposomes Increases Sensitivity of Cancer Cells to Chemotherapeutic Agents
Authors: Liu Xiaoli , Madhankumar A.B. , Slagle-Webb Becky , Sheehan Jonas M. , Surguladze Nodar , Connor James R. 
Published: March 2011

Abstract
Approximately half of all gliomas are resistant to chemotherapy, and new therapeutic strategies are urgently needed to treat this cancer. We hypothesized that disrupting iron homeostasis in glioma cells could block tumor growth, based on an acute requirement for high levels of iron to meet energy requirements associated with their rapid growth. Ferritin is best known as an intracellular iron storage protein, but it also localizes to tumor cell nuclei where it seems to protect DNA from oxidative damage and to promote transcription. In this study, we hypothesize that silencing the H-ferritin (heavy chain ferritin) gene could increase tumor sensitivity to chemotoxins. To test this hypothesis, H-ferritin siRNA was delivered to several human cancer cell lines by using cationic liposomes (C-liposome). H-ferritin siRNA decreased protein expression by 80% within 48 hours, and this decrease was associated with more than 50% decrease in the LD50 for DNA-alkylating agent carmustine (BCNU), which is commonly used to treat glioma in clinic. In a subcutaneous mouse model of human glioma, intratumoral injections of liposomes containing H-ferritin siRNA reduced the effective dose of BCNU needed for tumor suppression by more than 50%. A plasmid supercoil relaxation assay showed that H-ferritin specifically and directly protected DNA from BCNU treatment. H-ferritin siRNA additionally seemed to increase apoptosis in glioma cells in vitro upon H-ferritin knockdown. Overall, our results illustrate how silencing H-ferritin can effectively sensitize tumors to chemotherapy and also show the ability of C-liposomes to serve as a novel in vivo delivery tool for siRNAs. Cancer Res; 71(6); 2240–9. ©2011 AACR.
miR-218 Suppresses Nasopharyngeal Cancer Progression through Downregulation of Survivin and the SLIT2-ROBO1 Pathway
Authors: Alajez Nehad M. , Lenarduzzi Michelle , Ito Emma , Hui Angela B.Y. , Shi Wei , Bruce Jeff , Yue Shijun , Huang Shao H. , Xu Wei , Waldron John , O'Sullivan Brian , Liu Fei-Fei 
Published: March 2011

Abstract
Nasopharayngeal carcinoma (NPC) is an Epstein–Barr virus–associated malignancy most common in East Asia and Africa. Here we report frequent downregulation of the microRNA miR-218 in primary NPC tissues and cell lines where it plays a critical role in NPC progression. Suppression of miR-218 was associated with epigenetic silencing of SLIT2 and SLIT3, ligands of ROBO receptors that have been previously implicated in tumor angiogenesis. Exogenous expression of miR-218 caused significant toxicity in NPC cells in vitro and delayed tumor growth in vivo. We used an integrated trimodality approach to identify targets of miR-218 in NPC, cervical, and breast cell lines. Direct interaction between miR-218 and the 3′-untranslated regions (UTR) of mRNAs encoding ROBO1, survivin (BIRC5), and connexin43 (GJA1) was validated in a luciferase-based transcription reporter assay. Mechanistic investigations revealed a negative feedback loop wherein miR-218 regulates NPC cell migration via the SLIT-ROBO pathway. Pleotropic effects of miR-218 on NPC survival and migration were rescued by enforced expression of miR-218–resistant, engineered isoforms of survivin and ROBO1, respectively. In clinical specimens of NPC (n = 71), ROBO1 overexpression was significantly associated with worse overall (P = 0.04, HR = 2.4) and nodal relapse-free survival (P = 0.008, HR = 6.0). Our findings define an integrative tumor suppressor function for miR-218 in NPC and further suggest that restoring miR-218 expression in NPC might be useful for its clinical management. Cancer Res; 71(6); 2381–91. ©2011 AACR.
CREB Is a Novel Nuclear Target of PTEN Phosphatase
Authors: Gu Tingting , Zhang Zhong , Wang Jianli , Guo Junyi , Shen Wen Hong , Yin Yuxin 
Published: March 2011

Abstract
PTEN phosphatase is a potent tumor suppressor that regulates multiple cellular functions. In the cytoplasm, PTEN dephosphorylates its primary lipid substrate, phosphatidylinositol 3,4,5-trisphosphate, to antagonize the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway. It has also become increasingly evident that PTEN functions in the nucleus and may play an important part in transcription regulation, but its nuclear targets remain elusive. In this report, we demonstrate the transcription factor cyclic AMP response element-binding protein (CREB) is a protein target of PTEN phosphatase and that PTEN deficiency leads to CREB phosphorylation independent of the PI3K/AKT pathway. Using confocal immunofluorescence and reciprocal immunoprecipitation, we further show that PTEN colocalizes with CREB and physically interacts with CREB. Moreover, we use both in vitro and in vivo experiments to show PTEN can dephosphorylate CREB in a phosphatase-dependent manner, suggesting that CREB is a substrate of PTEN nuclear phosphatase. Loss of Pten results in an elevated RNA level of multiple CREB transcriptional targets and increased cell proliferation, which can be reversed by a nonphosphorylatable CREB mutant or knockdown of CREB. These data reveal a mechanism for PTEN modulation of CREB-mediated gene transcription and cell growth. Our study thus characterizes PTEN as a nuclear phophatase of a transcription factor and identifies CREB as a novel protein target of PTEN phosphatase, which contributes to better understanding of PTEN function in the nucleus. Cancer Res; 71(8); 2821–5. ©2011 AACR.
Functional Cooperation of RKTG with p53 in Tumorigenesis and Epithelial–Mesenchymal Transition
Authors: Jiang Yuhui , Xie Xiaoduo , Li Zhigang , Wang Zheng , Zhang Yixuan , Ling Zhiqiang , Pan Yi , Wang Zhenzhen , Chen Yan 
Published: March 2011

Abstract
Raf kinase trapping to Golgi (RKTG) is a potential tumor suppressor gene due to its negative roles in regulating Ras/Raf/MEK/ERK (extracellular signal–regulated kinase) pathway and GPCR (G protein–coupled receptor) Gβγ subunit signaling. Interestingly, RKTG-deficient mice are free of tumors, although they are prone to form skin cancer on carcinogen administration. On the other hand, p53 is a well-characterized tumor suppressor gene and p53 heterozygous mice develop sarcoma and other tumors starting from 12 months of age. In RKTG-null mouse embryonic fibroblasts, lypophosphatidic acid (LPA), but not EGF (epidermal growth factor), could stimulate hyperphosphorylation of AKT and GSK3β, accompanied by increases in phosphorylation of p53 at Ser15 and accumulation of p53, as well as its target genes p21 and p16. Spontaneous skin cancer–like tumors were detected in about 25% of RKTG nullizygous and p53 heterozygous mice within 7 months of age. Hyperplasia and epithelial–mesenchymal transition (EMT) were observed in the tumor-overlying epidermis, in which LOH of p53 occurred and EMT features emerged. In p53-mutated A431 epithelial carcinoma cells, knockdown of RKTG led to enhancement of LPA-stimulated AKT and GSK3β phosphorylation, together with increased accumulation of β-catenin and appearance of EMT features that were antagonized by p53 overexpression. In HepG2 epithelial cells, LPA-stimulated AKT phosphorylation and EMT features reached maximum when both RKTG and p53 were simultaneously silenced. In summary, these results not only indicate that RKTG has an in vivo tumor suppressor function to cooperate with p53 in tumorigenesis but also suggest that p53 has an EMT checkpoint function and the loss of this function can combine with loss of RKTG to drive EMT and tumor progression. Cancer Res; 71(8); 2959–68. ©2011 AACR.
A Developmental Taxonomy of Glioblastoma Defined and Maintained by MicroRNAs
Authors: Kim Tae-Min , Huang Wei , Park Richard , Park Peter J. , Johnson Mark D. 
Published: March 2011

Abstract
mRNA expression profiling has suggested the existence of multiple glioblastoma subclasses, but their number and characteristics vary among studies and the etiology underlying their development is unclear. In this study, we analyzed 261 microRNA expression profiles from The Cancer Genome Atlas (TCGA), identifying five clinically and genetically distinct subclasses of glioblastoma that each related to a different neural precursor cell type. These microRNA-based glioblastoma subclasses displayed microRNA and mRNA expression signatures resembling those of radial glia, oligoneuronal precursors, neuronal precursors, neuroepithelial/neural crest precursors, or astrocyte precursors. Each subclass was determined to be genetically distinct, based on the significant differences they displayed in terms of patient race, age, treatment response, and survival. We also identified several microRNAs as potent regulators of subclass-specific gene expression networks in glioblastoma. Foremost among these is miR-9, which suppresses mesenchymal differentiation in glioblastoma by downregulating expression of JAK kinases and inhibiting activation of STAT3. Our findings suggest that microRNAs are important determinants of glioblastoma subclasses through their ability to regulate developmental growth and differentiation programs in several transformed neural precursor cell types. Taken together, our results define developmental microRNA expression signatures that both characterize and contribute to the phenotypic diversity of glioblastoma subclasses, thereby providing an expanded framework for understanding the pathogenesis of glioblastoma in a human neurodevelopmental context. Cancer Res; 71(9); 3387–99. ©2011 AACR.
Targeting Galectin-1 in Carcinoma-Associated Fibroblasts Inhibits Oral Squamous Cell Carcinoma Metastasis by Downregulating MCP-1/CCL2 Expression
Authors: Wu Ming-Heng , Hong Hsiao-Chin , Hong Tse-Ming , Chiang Wei-Fan , Jin Ying-Tai , Chen Yuh-Ling 
Published: March 2011

AbstractPurpose: Carcinoma-associated fibroblasts (CAFs) in tumor stroma play an important role in tumor progression and have been associated with a poor prognosis in oral squamous cell carcinoma (OSCC). However, how CAFs influence OSCC malignancy and whether normalizing CAFs inhibits cancer progression remain unclear.Experimental Design: The relationship between the expression of Galectin-1 (Gal-1) and alpha-smooth muscle actin (α-SMA, a CAF marker) in OSCC patient samples and primary cultured CAFs was examined by quantitative real-time PCR, Western blotting, and immunofluorescence. To examine the effect of Gal-1 on CAF activation and CAF-mediated tumor invasion and migration in vitro, Gal-1 expression was knocked down by small hairpin RNA. Finally, cancer cells and CAFs were coimplanted into SCID mice to evaluate the effect of Gal-1 on CAF-modulated tumor progression in vivo.Results: Gal-1 expression is positively associated with α-SMA in the stroma of OSCC specimens. Gal-1 knockdown decreases activated CAF characteristics, resulting in a decrease in α-SMA expression and extracellular matrix protein production. Notably, blocking Gal-1 expression significantly inhibits CAF-conditioned medium-induced tumor cell migration and invasion, possibly by reducing the production of monocyte chemotactic protein-1 (MCP-1/CCL2). MCP-1 induces the migration of OSCC cells by binding to the receptor CCR2; adding an MCP-1 antibody to CAF-conditioned medium that inhibits the interaction between MCP-1 and CCR2 abolishes migration. Finally, we found that Gal-1 knockdown in CAFs significantly reduces CAF-augmented tumor growth and metastasis in vivo.Conclusions: Our findings demonstrate that Gal-1 regulates CAF activation and indicate that targeting Gal-1 in CAFs inhibits OSCC metastasis by modulating MCP-1 expression. Clin Cancer Res; 17(6); 1306–16. ©2011 AACR.