bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wild-Type BRCA1, but not Mutated BRCA1, Regulates the Expression of the Nuclear Form of β-Catenin
Authors: Li Huchun , Sekine Masayuki , Tung Nadine , Avraham Hava Karsenty 
Published: March 2010

Abstract
BRCA1 is an essential caretaker protein in the surveillance of DNA damage, is mutated in ∼50% of all hereditary breast cancer cases, and its expression is frequently decreased in sporadic breast cancer. β-Catenin is a multifunctional protein that forms adhesion complex with E-cadherins, α-catenin, and actin, and plays a central role in Wnt signaling through its nuclear translocation and activation of β-catenin–responsive genes. Although significant progress has been made in understanding the Wnt/β-catenin and BRCA1 signaling cascades, it is not known whether there is a link between β-catenin and BRCA1. We observed that the expression of the active nuclear form of β-catenin (also known as ABC, Ser37/Thr41-nonphosphorylated β-catenin, dephosphorylated β-catenin) was lower or absent in the nucleus in most BRCA1 familial breast cancer tissues (17 cases) compared with sporadic breast cancer (14 samples) and normal breast tissues. Wild-type-BRCA1, but not mutated BRCA1, interacted with β-catenin and increased the levels of β-catenin protein expression in vitro. Furthermore, H2O2 induced the interaction of the nuclear form of β-catenin with BRCA1. The active form of β-catenin protein was downregulated upon exposure to H2O2 in the nucleus of BRCA1-deficient HCC1937 breast cancer cells, whereas reconstitution of WT-BRCA1 in HCC1937 cells inhibited this downregulation. This study provides evidence of a novel interaction between BRCA1 and β-catenin, and that loss of BRCA1 leads to impaired expression of the nuclear form of β-catenin, which may contribute to the pathogenesis of breast cancer. Mol Cancer Res; 8(3); 407–20
Covalent antithrombin-heparin effect on thrombin-thrombomodulin and activated protein C reaction with factor V/Va
Authors: Walderveen Maria Christina Van , Berry Leslie Roy , Atkinson Helen Mary , Chan Anthony Kam Chuen 
Published: March 2010

SummaryThrombomodulin (TM), which variably contains a chondroitin sulfate (±CS), forms an anticoagulant complex with thrombin (IIa). IIaTM(±CS) converts protein C (PC) into activated PC (APC), which then inactivates activated factors V (FVa) and VIII (FVIIIa). This reduces prothrombinase and tenase complexes that generate IIa. Heparin (H) increases the rate of IIa-TM inhibition by antithrombin (AT) and enhances FV cleavage by APC. Our novel covalent AT-H (ATH) product, has superior anticoagulant activity compared to AT + unfractionated H (UFH). We studied mechanisms by which ATH versus AT + UFH inhibits IIaTM(±CS), and ATH influences on APC cleavage of FV/FVa compared to UFH. Findings would determine how these reactions moderate ATH’s overall effects as an anticoagulant. Discontinuous second order rate inhibition assays of IIa-TM(±CS) inhibition by AT + UFH or ATH were performed in presence or absence of human umbilical vein endothelial cells (HUVECs). FV/FVa cleavage by APC in the presence of UFH or ATH was analysed by Western blots. ATH increased IIa-TM(±CS) inhibition to a greater degree than AT + UFH, both on plastic and HUVEC surfaces. Unlike UFH, ATH did not accelerate FV cleavage by APC, but ATH did enhance FVa cleavage relative to UFH. Increased IIa-TM inhibition by ATH downregulates PC activation. However, ATH does accelerate downstream inactivation of FVa, which increases its potency for IIa generation inhibition compared to UFH. This trend holds true in the presence of APC’s cofactor, protein S. Overall, ATH may have a balanced function towards inhibiting or accelerating PC pathway activities.
Role of glycoprotein Ibα mobility in platelet function
Authors: van der Wal Dianne , Verhoef Sandra , Schutgens Roger , Peters Marjolein , Wu Yaping , Akkerman Jan Willem 
Published: March 2010

SummaryIncubation at 0°C is known to expose β-N-acetyl-D-glucosamine residues on glycoprotein (GP) Ibα inducing receptor clustering and αMβ2-mediated platelet destruction by macrophages. Here we show that incubation at 0/37°C (4 hours at 0°C, followed by 1 hour at 37°C to mimic cold-storage and post-transfusion conditions) triggers a conformational change in the N-terminal flank (NTF, amino acids, aa 1–35) but not in aa 36–282 of GPIbα as detected by antibody binding. Addition of the sugar N-acetyl-D-glucosamine (GN) inhibits responses induced by 0/37°C. Incubation at 0°C shifts GPIbα from the membrane skeleton to the cytoskeleton. Different GPIbα conformations have little effect on VWF/ristocetin-induced aggregation, but arrest of NTF change by GN interferes with agglutination and spreading on a VWF-coated surface under flow. Strikingly, incubation at 0/37°C initiates thromboxane A2 formation through a von Willebrand factor (VWF)-independent and GPIbα-dependent mechanism, as confirmed in VWF- and GPIbαﺹdeficient platelets. We conclude that the NTF change induced by 0/37°C incubation reflects clustering of GPIbα supports VWF/ristocetin-induced agglutination and spreading and is sufficient to initiate platelet activation in the absence of VWF.
Thrombolysis for pulmonary embolism: Past, present and future
Authors: Lankeit Mareike , Konstantinides Stavros 
Published: March 2010

SummaryPatients with high-risk pulmonary embolism (PE), i.e. those with shock or hypotension at presentation, are at high risk of in-hospital death, particularly during the first hours after admission. A meta-analysis of trials which included haemodynamically compromised patients indicated that thrombolytic treatment significantly reduces the rate of inhospital death or PE recurrence. Therefore, thrombolysis should be administered to patients with high-risk PE unless there are absolute contraindications to its use. Uncontrolled data further suggest that thrombolysis may be a safe and effective alternative to surgery in patients with PE and free-floating thrombi in the right heart. On the other hand, normotensive patients generally have a favourable short-term prognosis if heparin anticoagulation is instituted promptly, and they are thus considered to have non-high-risk PE. Generally, the bleeding risk of thrombolysis appears to outweigh the clinical benefits of this treatment in patients without haemodynamic compromise. However, within the group of normotensive patients with PE, some may have evidence of right ventricular dysfunction on echocardiography or computed tomography, or of myocardial injury based on elevated cardiac biomarkers (troponin I or T, heart-type fatty acid-binding protein). These patients have an intermediate risk of an adverse outcome in the acute phase of PE. Existing data suggest that selected patients with intermediate-risk PE may benefit from early thrombolytic treatment, particularly if they have a low bleeding risk. However, controversy will continue to surround the optimal treatment for this group until the results of a large ongoing thrombolysis trial are available in a few years.
Effect of Shortening Deformity of the Clavicle on Scapular Kinematics
Authors: Matsumura Noboru , Ikegami Hiroyasu , Nakamichi Noriaki , Nakamura Toshiyasu , Nagura Takeo , Imanishi Nobuaki , Aiso Sadakazu , Toyama Yoshiaki 
Published: March 2010

Background In some short malunion cases, midshaft clavicular fractures are reported to result in unsatisfactory clinical outcomes. Shortening deformity of the clavicle could change the anatomical alignment of the shoulder girdle and is surmised to affect shoulder kinematics on arm movements. Nevertheless, no report has ever referred to documented changes. Hypothesis Scapular motion will change with clavicular shortening in cadaveric models. Study Design Controlled laboratory study. Methods Twelve cadaveric shoulders were used, and sequential clavicular shortening by 0%, 5%, 10%, 15%, and 20% from the original length was simulated in this study. The scapulothoracic motion during passive arm elevation in 3 planes was monitored using an electromagnetic tracking device. Differences in kinematics of the scapula between the 0% shortening models and the other 4 experimental groups were analyzed. Results During arm elevation, posterior tilting and external rotation of the scapula significantly decreased with ≥10% shortening of the clavicle. Decreased posterior tilting was found with a shorter clavicle and at higher positions of arm elevation in all planes and became obvious during coronal plane elevation. Upward rotation of the scapula did not change with shortening at any elevated arm positions. Conclusion The findings of this study clearly indicated that shortening of the clavicle affects the kinematics in the shoulder girdle. Clinical Relevance The results of this cadaveric study suggest that clavicular shortening of ≥10% affects scapular kinematics and might produce clinical symptoms.
Place, Space, and Representation
Authors: Jain Jyotindra 
Published: March 2010

Building upon the notion that “space is a practiced place” and that spatial practices activate places, the article explores Indian pilgrimage maps and painted narrative panels of itinerant picture showmen as examples of portable geographies. It argues that these materials act as condensed and iconized places of pilgrimage activated in the case of maps by their worship and by audio-visual performance in the case of the painted narrative panels of Dev Narayan. These visual forms are not merely imaginary or imaged representations of particular sacred places but are representations of a very specific type: akin to mobile shrines, they facilitate the translocation of ritual, symbolic and performative functions. When delineated as pilgrimage maps, picture showmen’s panels, or theater backdrops, sacred place and sacred space become iconized and transportable. In turn, they become vehicles for the imaginary transportation of audiences into their spatial form.
Prevalence of multiple sclerosis in Denmark 1950—2005
Authors: Bentzen Joan , Meulengracht Flachs Esben , Stenager Egon , Brønnum-Hansen Henrik , Koch-Henriksen Nils 
Published: March 2010

Multiple sclerosis is an inflammatory disease of the central nervous system of unknown aetiology. Its prevalence varies by ethnicity and place: persons of northern European descent are at increased risk while persons living at lower latitudes appear to be protected against the disease. The Danish Multiple Sclerosis Registry is a national registry established in 1956 after a population-based survey which receives information from numerous sources. It is considered to be more than 90% complete, with a validity of 94%. Using data from the Registry, we calculated prevalences per 100,000 inhabitants. The standardized prevalence of multiple sclerosis increased from 58.8 (95% confidence interval: 54.9—62.7) in 1950 to 154.5 per 100,000 (95% confidence interval: 148.8—160.2) in 2005, and the female to male ratio increased from 1.31 in 1950 to 2.02 in 2005. The increase in prevalence is due to both increased survival of multiple sclerosis patients and an increased incidence rate. The rise in prevalence in the past 50 years is probably due more to environmental factors than to genetic changes in the Danish population. Among women, environmental changes could include older age at first birth, use of oral contraceptives, or changes in sun behaviour and/or vitamin D status.
Leadership Lessons from the Fast Track Programme for Teachers in England
Authors: Jones Jeffrey 
Published: March 2010

The Fast Track Teaching (FTT) programme in England, developed and funded by central government, is an accelerated leadership development programme designed for teachers in the early years of their careers. It was intended to promote their retention and rapid promotion in the profession through advancing their leadership skills. It provides a highly personalized programme of coaching, mentoring and development activities for teachers. Since its inception in 2001 annual recruitment has grown substantially and there are currently around 2000 teachers on the programme. The future of the programme is currently under review. This article reports the findings of a small-scale evaluation study of the experiences of a small number of teachers on the FTT programme currently. It attempts to capture participants’ perspectives on the programme and to contribute to the current knowledge base on accelerated leadership development. Eleven teachers from the programme were interviewed. The semi-structured interview schedule covered all aspects of provision from recruitment, through assessment to conclusion of the participants’ programme. The main findings from the research are as follows: (1) All the participants were overwhelmingly positive about their experience on the programme. They found it inspirational and highly motivating. They also found it extremely supportive, allowing them to make a strong positive difference to the schools they were in. (2) All the participants believed that the programme had led to their more rapid career progress than otherwise would have been the case. Almost half had taken the opportunity to take higher degree programmes as part of the FTT offer. (3) All agreed that the personalization of the programme, the work of the personal leadership tutors and the support of participating head teachers were significant factors in the success of the programme. (4) All those interviewed found it difficult to suggest improvements for the programme. Minor difficulties encountered were cast as isolated events and not reflective of structural limitations of the provision.
Hygiene inspections on passenger ships in Europe - an overview
Authors: Mouchtouri Varvara A , Westacott Sandra , Nichols Gordon , Riemer Tobias , Skipp Mel , Bartlett Christopher LR , Kremastinou Jenny , Hadjichristodoulou Christos ,   the SHIPSAN partnership**
Published: March 2010

Abstract

Background
Hygiene inspections on passenger ships are important for the prevention of communicable diseases. The European Union (EU) countries conduct hygiene inspections on passenger ships in order to ensure that appropriate measures have been taken to eliminate potential sources of contamination which could lead to the spread of communicable diseases. This study was implemented within the framework of the EU SHIPSAN project and it investigates the legislation applied and practices of hygiene inspections of passenger ships in the EU Member States (MS) and European Free Trade Association countries.

Methods
Two questionnaires were composed and disseminated to 28 countries. A total of 92 questionnaires were completed by competent authorities responsible for hygiene inspections (n = 48) and the creation of legislation (n = 44); response rates were 96%, and 75.9%, respectively.

Results
Out of the 48 responding authorities responsible for hygiene inspections, a routine programme was used by 19 (39.6%) of these to conduct inspections of ships on national voyages and by 26 (54.2%) for ships on international voyages. Standardised inspection forms are used by 59.1% of the authorities. A scoring inspection system is applied by five (11.6%) of the 43 responding authorities. Environmental sampling is conducted by 84.1% of the authorities (37 out of 44). The inspection results are collected and analysed by 54.5% (24 out of 44) of the authorities, while 9 authorities (20.5%) declared that they publish the results. Inspections are conducted during outbreak investigations by 75% and 70.8% of the authorities, on ships on national and international voyages, respectively. A total of 31 (64.6%) and 39 (81.3%) authorities conducted inspections during complaint investigations on ships on international and on national voyages, respectively. Port-to-port communication between the national port authorities was reported by 35.4% (17 out of 48) of the responding authorities and 20.8% (10 out of 48) of the port authorities of other countries.

Conclusion
This study revealed a diversity of approaches and practices in the conduct of inspections, differences in the qualifications/knowledge/experience of inspectors, the legislation applied during inspections, and the lack of communication and training among many EU countries. An integrated European inspection programme involving competent expert inspectors in each EU Member States and special training for ship hygiene delivered to crew members and inspectors would help to minimize the risk of communicable diseases. Common inspection tools at a European level for hygiene inspection practices and port-to-port communication are needed.
Authors' opinions on publication in relation to annual performance assessment
Authors: Walker Robin L , Sykes Lindsay , Hemmelgarn Brenda R , Quan Hude 
Published: March 2010

Abstract

Background
In the past 50 years there has been a substantial increase in the volume of published research and in the number of authors per scientific publication. There is also significant pressure exerted on researchers to produce publications. Thus, the purpose of this study was to survey corresponding authors in published medical journals to determine their opinion on publication impact in relation to performance review and promotion.

Methods
Cross-sectional survey of corresponding authors of original research articles published in June 2007 among 72 medical journals. Measurement outcomes included the number of publications, number of authors, authorship order and journal impact factor in relation to performance review and promotion.

Results
Of 687 surveys, 478 were analyzed (response rate 69.6%). Corresponding authors self-reported that number of publications (78.7%), journal impact factor (67.8%) and being the first author (75.9%) were most influential for their annual performance review and assessment. Only 17.6% of authors reported that the number of authors on a manuscript was important criteria for performance review and assessment. A higher percentage of Asian authors reported that the number of authors was key to performance review and promotion (41.4% versus 7.8 to 22.2%). compared to authors from other countries.

Conclusions
The number of publications, authorship order and journal impact factor were important factors for performance reviews and promotion at academic and non-academic institutes. The number of authors was not identified as important criteria. These factors may be contributing to the increase in the number of authors per publication.
Suppressive effect of azithromycin on Plasmodium berghei mosquito stage development and apicoplast replication
Authors: Shimizu Shoichi , Osada Yoshio , Kanazawa Tamotsu , Tanaka Yoshiya , Arai Meiji 
Published: March 2010

Abstract

Background
Azithromycin (AZM) is a macrolide antibiotic that displays an excellent safety profile even in children and pregnant women and has been shown to have anti-malarial activity against blood stage Plasmodium falciparum. This study evaluated the transmission-blocking effect of AZM using a rodent malaria model.

Methods
AZM-treated mice infected with Plasmodium berghei were exposed to Anopheles stephensi mosquitoes, followed by the observation of parasite development at different phases in the mosquito, i.e., ookinetes in the midgut, oocysts on the midgut, and sporozoites in the midgut and salivary glands. Furthermore, to evaluate the effect on organelle replication of each stage, quantitative real-time PCR analysis was performed.

Results
The inhibitory effect of AZM was noticeable in both gametocyte-ookinete transformation in the midgut and sporozoite production in the oocyst, while the latter was most remarkable among all the developmental phases examined. Real-time PCR analysis revealed that AZM suppressed apicoplast replication at the period of sporozoite production in oocysts.

Conclusions
AZM inhibits parasite development in the mosquito stage, probably through the same mechanism as in the liver and blood stages. Such a multi-targeting anti-malarial, along with its safety, would be ideal for mass drug administration in malaria control programmes.
Specific effects of bortezomib against experimental malignant pleural effusion: a preclinical study
Authors: Psallidas Ioannis , Karabela Sophia P , Moschos Charalampos , Sherrill Taylor P , Kollintza Androniki , Magkouta Sophia , Theodoropoulou Panagiota , Roussos Charis , Blackwell Timothy S , Kalomenidis Ioannis , Stathopoulos Georgios T 
Published: March 2010

Abstract

Background
We have previously shown that nuclear factor (NF)-κ B activation of mouse Lewis lung carcinoma (LLC) specifically promotes the induction of malignant pleural effusions (MPE) by these cells. In the present studies we hypothesized that treatment of immunocompetent mice with bortezomib tailored to inhibit cancer cell NF-κ B activation and not proliferation specifically inhibits MPE formation by LLC cells.

Results
Treatment of LLC cells with low concentrations of bortezomib (100 ng/ml) inhibited NF-κ B activation and NF-κ B-dependent transcription, but not cellular proliferation. Bortezomib treatment of immunocompetent C57BL/6 mice bearing LLC-induced subcutaneous tumors and MPEs significantly blocked tumor-specific NF-κ B activation. However, bortezomib treatment did not impair subcutaneous LLC tumor growth, but was effective in limiting LLC-induced MPE. This specific effect was evidenced by significant reductions in effusion accumulation and the associated mortality and was observed with both preventive (beginning before MPE formation) and therapeutic (beginning after MPE establishment) bortezomib treatment. The favorable impact of bortezomib on MPE was associated with suppression of cardinal MPE-associated phenomena, such as inflammation, vascular hyperpermeability, and angiogenesis. In this regard, therapeutic bortezomib treatment had identical favorable results on MPE compared with preventive treatment, indicating that the drug specifically counteracts effusion formation.

Conclusions
These studies indicate that proteasome inhibition tailored to block NF-κ B activation of lung adenocarcinoma specifically targets the effusion-inducing phenotype of this tumor. Although the drug has limited activity against advanced solid lung cancer, it may prove beneficial for patients with MPE.