bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction between FGFR-2, STAT5, and Progesterone Receptors in Breast Cancer
Authors: Cerliani Juan P. , Guillardoy Tomás , Giulianelli Sebastián , Vaque José P. , Gutkind J. Silvio , Vanzulli Silvia I. , Martins Rubén , Zeitlin Eduardo , Lamb Caroline A. , Lanari Claudia
Published: April 2011

Fibroblast growth factor (FGF) receptor 2 (FGFR-2) polymorphisms have been associated with an increase in estrogen receptor and progesterone receptor (PR)-positive breast cancer risk; however, a clear mechanistic association between FGFR-2 and steroid hormone receptors remains elusive. In previous works, we have shown a cross talk between FGF2 and progestins in mouse mammary carcinomas. To investigate the mechanisms underlying these interactions and to validate our findings in a human setting, we have used T47D human breast cancer cells and human cancer tissue samples. We showed that medroxyprogesterone acetate (MPA) and FGF2 induced cell proliferation and activation of ERK, AKT, and STAT5 in T47D and in murine C4-HI cells. Nuclear interaction between PR, FGFR-2, and STAT5 after MPA and FGF2 treatment was also showed by confocal microscopy and immunoprecipitation. This effect was associated with increased transcription of PRE and/or GAS reporter genes, and of PR/STAT5-regulated genes and proteins. Two antiprogestins and the FGFR inhibitor PD173074, specifically blocked the effects induced by FGF2 or MPA respectively. The presence of PR/FGFR-2/STAT5 complexes bound to the PRE probe was corroborated by using NoShift transcription and chromatin immunoprecipitation of the MYC promoter. Additionally, we showed that T47D cells stably transfected with constitutively active FGFR-2 gave rise to invasive carcinomas when transplanted into NOD/SCID mice. Nuclear colocalization between PR and FGFR-2/STAT5 was also observed in human breast cancer tissues. This study represents the first demonstration of a nuclear interaction between FGFR-2 and STAT5, as PR coactivators at the DNA progesterone responsive elements, suggesting that FGFRs are valid therapeutic targets for human breast cancer treatment. Cancer Res; 71(10); 3720–31. ©2011 AACR.
Efficacy, Tolerability and Patient Benefit of Ultrasound-Assisted Wound Treatment versus Surgical Debridement: A Randomized Clinical Study
Authors: Herberger Katharina , Franzke Nadine , Blome Christine , Kirsten Nathalie , Augustin Matthias
Published: April 2011

Background: Low-frequency ultrasound has been shown to be an alternative to surgical wound debridement (WD) to stimulate wound healing; however, few data are available. Objective: To compare the efficacy, tolerability and benefit of both wound treatment methods. Methods: A monocentric prospective randomized-controlled clinical study assessing patient-reported outcomes and clinical efficacy of ultrasound-assisted wound treatment (UAW) compared to WD. Results: In total, 67 patients were treated. Efficacy and tolerability were found to be good for both treatments, with 88% of UAW and 85.2% of WD patients experiencing more-than-minimal patient benefit. Quality of life improved significantly. Wound status improved and pain decreased in both groups. Conclusion: Compared to the gold standard (i.e. WD), UAW displays the same high efficacy, comparable patient benefit and improved quality of life. Both procedures are equally suitable for highly beneficial guideline-based treatment of chronic wounds.
Persistent Racial Disparities in Survival After Heart Transplantation
Authors: Liu Vincent , Bhattacharya Jay , Weill David , Hlatky Mark A.
Published: April 2011

Background—

Racial and ethnic disparities are well documented in many areas of health care, but have not been comprehensively evaluated among recipients of heart transplants.

Methods and Results—

We performed a retrospective cohort study of 39075 adult primary heart transplant recipients from 1987 to 2009 using national data from the United Network of Organ Sharing and compared mortality for nonwhite and white patients using the Cox proportional hazards model. During the study period, 8082 nonwhite and 30 993 white patients underwent heart transplantation. Nonwhite heart transplant recipients increased over time, comprising nearly 30% of transplantations since 2005. Nonwhite recipients had a higher clinical risk profile than white recipients at the time of transplantation, but had significantly higher posttransplantation mortality even after adjustment for baseline risk. Among the nonwhite group, only black recipients had an increased risk of death compared with white recipients after multivariable adjustment for recipient, transplant, and socioeconomic factors (hazard ratio, 1.34; 95% confidence interval, 1.21 to 1.47;
P
<0.001). Five-year mortality was 35.7% (95% confidence interval, 35.2 to 38.3) among black and 26.5% (95% confidence interval, 26.0 to 27.0) among white recipients. Black patients were more likely to die of graft failure or a cardiovascular cause than white patients, but less likely to die of infection or malignancy. Although mortality decreased over time for all transplant recipients, the disparity in mortality between blacks and whites remained essentially unchanged.

Conclusions—

Black heart transplant recipients have had persistently higher mortality than whites recipients over the past 2 decades, perhaps because of a higher rate of graft failure.
Associations Between Outpatient Heart Failure Process-of-Care Measures and Mortality
Authors: Fonarow Gregg C. , Albert Nancy M. , Curtis Anne B. , Gheorghiade Mihai , Heywood J. Thomas , Liu Yang , Mehra Mandeep R. , O'Connor Christopher M. , Reynolds Dwight , Walsh Mary Norine , Yancy Clyde W.
Published: April 2011

Background—

Assessment of the quality of care for outpatients with heart failure (HF) has focused on the development and use of process-based performance measures, with the supposition that these care process measures are associated with clinical outcomes. However, this association has not been evaluated for current and emerging outpatient HF measures.

Methods and Results—

Performance on 7 HF process measures (4 current and 3 emerging) and 2 summary measures was assessed at baseline in patients from 167 US outpatient cardiology practices with patients prospectively followed up for 24 months. Participants included 15 177 patients with reduced left ventricular ejection fraction (≤35%) and chronic HF or post–myocardial infarction. Multivariable analyses were performed to assess the process-outcome relationship for each measure in eligible patients. Vital status was available for 11 621 patients. The mortality rate at 24 months was 22.1%. Angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use, β-blocker use, anticoagulant therapy for atrial fibrillation, cardiac resynchronization therapy, implantable cardioverter-defibrillators, and HF education for eligible patients were each independently associated with improved 24-month survival, whereas aldosterone antagonist use was not. The all-or-none and composite care summary measures were also independently associated with improved survival. Each 10% improvement in composite care was associated with a 13% lower odds of 24-month mortality (adjusted odds ratio, 0.87; 95% confidence interval, 0.84 to 0.90;
P
<0.0001).

Conclusions—

Current and emerging outpatient HF process measures are positively associated with patient survival. These HF measures may be useful for assessing and improving HF care.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00303979.
Pressor and Renal Hemodynamic Effects of the Novel Angiotensin A Peptide Are Angiotensin II Type 1A Receptor Dependent
Authors: Yang Rui , Smolders Ilse , Vanderheyden Patrick , Demaegdt Heidi , Van Eeckhaut Ann , Vauquelin Georges , Lukaszuk Aneta , Tourwé Dirk , Chai Siew Yeen , Albiston Anthony L. , Nahmias Clara , Walther Thomas , Dupont Alain G.
Published: April 2011

Recently, a new derivative of angiotensin (Ang) II, called “Ang A,” has been discovered to be present in plasma of healthy humans and, in increased concentrations, in end-stage renal failure patients. The objectives of the study were to investigate the blood pressure and renal hemodynamic responses to Ang A in normotensive and hypertensive rats and in genetically modified mice and the binding properties of Ang A to Ang II type 1 (AT
1
) or Ang II type 2 (AT
2
) receptors. Intravenous and intrarenal administration of Ang A induced dose-dependent pressor and renal vasoconstrictor responses in normotensive rats, which were blocked by the AT
1
receptor antagonist candesartan but were not altered by the AT
2
receptor ligands PD123319, CGP42112A, or compound 21. Similar responses were observed after intravenous administration in spontaneously hypertensive rats. Deletion of AT
1a
receptors in mice almost completely abolished the pressor and renal vasoconstrictor responses to Ang A, indicating that its effects are mediated via AT
1a
receptors. Ang A was less potent than Ang II in vivo. The in vitro study demonstrated that Ang A is a full agonist for AT
1
receptors, with similar affinity for AT
1
and AT
2
receptors as Ang II. Overall, the responses to Ang A and Ang II were similar. Ang A has no physiological role to modulate the pressor and renal hemodynamic effects of Ang II.
Unsupervised Learning of Morphology
Authors: Hammarström Harald , Borin Lars
Published: April 2011

This article surveys work on Unsupervised Learning of Morphology. We define Unsupervised Learning of Morphology as the problem of inducing a description (of some kind, even if only morpheme-segmentation) of how orthographic words are built up given only raw text data of a language. We briefly go through the history and motivation of the this problem. Next, over 200 items of work are listed with a brief characterization, and the most important ideas in the field are critically discussed. We summarize the achievements so far and give pointers for future developments.
Postnational Aesthetics and the Work of Mourning in Ahmed Ali’s Twilight in Delhi
Authors: Padamsee Alex
Published: April 2011

One of the first novels written in English by an Indian Muslim, Ahmed Ali’s Twilight in Delhi (1940) has in many ways suffered the fate of extinction it seems to describe. Critical interpretations have confined it to a purely nostalgic portrait of a moribund Indo-Muslim society, unproblematically situated within a European realist aesthetic. In contrast, I argue Ali’s original location as an Urdu writer and the narrative’s sustained engagement with Urdu poetry do not merely lend authenticity to the elegiac tone of his portrait, they constitute a complex challenge to the priority of realism and the ostensible trope of Muslim cultural extinction being narrated. Contextualizing the novel within an evolving Urdu literary modernity since the late nineteenth century, I suggest the relevance of a continually reinvented poetics of loss that, on the eve of Partition, opens up discreet canons and communities to the politics of mourning and the absent presence they seek to foreclose.
Local Cosmopolitans in Colonial West Africa
Authors: Newell Stephanie
Published: April 2011

Historians of imperialism and postcolonial literary scholars have inherited a series of derogatory categories from colonial discourse, labels that were kept firmly in place by local elites in their anti-colonial cultural nationalism. In particular, in the colonial period the category of “mimic” was frequently used to keep distinctive social classes (and also ethnic groups) out of the political sphere. By continuing to recognize and debate mimicry, we indirectly inherit this negative bias. This article debates the ways in which cosmopolitan theory can help us to see the ambivalent mimic-man in a slightly different light from received opinion. If we re-classify colonial “mimics” as cosmopolitans or, more accurately, as local cosmopolitans, an array of new cultural and historical questions comes to the fore highlighting the relationships between elites and sub-elites, and the politics of representation in local contexts.
Utopian Cosmopolitanism and the Conscious Pariah: Harare, Ramallah, Cairo
Authors: Rooney Caroline
Published: April 2011

This article entertains the possibility that new, locally-embedded cosmopolitanisms, critical of the violence inflicted by various forms of colonialism and globalization, are not just a matter of locus, or location, or topos, but also a question of the utopian. I begin with some autobiographically based observations related to a certain barely-documented social formation I witnessed as a young woman in colonial Rhodesia, and develop the scope of analysis by relating the notion of utopian solidarity among pariahs to cultural imaginings of three differently cosmopolitan cities. It will be proposed that what is at stake in defining utopian cosmopolitanism is a certain cultural metaphori city (a term that will be gradually explicated), encapsulated here in the process of tracing submerged similarities in the cultural histories of Harare, Ramallah and Cairo, and engaging with the work of Dambudzo Marechera, Mourid Barghouti, Alaa Al Aswany and Ahdaf Soueif.
“The Working Side of Art”: Richard Grant in Conversation with Anouk Lang
Authors: Grant Richard , Lang Anouk
Published: April 2011

In this interview with Anouk Lang, the poet Richard Grant discusses his journey to becoming a professional performance poet: how he first came into contact with the dub poetry scene at university, his time as the Birmingham poet laureate in 2005-06, and his work with other spoken word poets at festivals, performances and school workshops around the UK. Topics covered include the role of live poetry in a culture in which sales of print publications are falling and new technologies are enabling writers to reach new audiences, poetry as a tool for confronting social issues such as racial conflict, the task of the poet laureate in relation to the city and the community, and generational, cultural and class divides in the contemporary British arts world.
The Mathematics Education of Future Primary and Secondary Teachers: Methods and Findings from the Teacher Education and Development Study in Mathematics
Authors: Tatto Maria Teresa , Senk Sharon
Published: April 2011

In 2005, the International Association for the Evaluation of Educational Achievement (IEA), Michigan State University, and the Australian Council for Educational Research took an important step in advancing the field of education by partnering to develop and implement the first international and comparative study of mathematics teacher education. The study was made possible by the substantial funding received from the National Science Foundation, the IEA, and the collaboration of 17 participating countries. The purpose of this article is to illustrate the methodology used in this major cross-national study of teacher education—the IEA Teacher Education and Development Study in Mathematics, known as TEDS-M—and to share its main findings related to the mathematical preparation of future teachers.
The Effect of Productive Activities on Depressive Symptoms Among Older Adults With Dual Sensory Loss
Authors: McDonnall Michele Capella
Published: April 2011

The purpose of this study was to evaluate the ability of three productive activities (paid employment, volunteer work, and informal helping) to mitigate the negative effects of dual sensory loss (DSL) on depressive symptoms among older adults. Multilevel modeling was used to analyze longitudinal data from the nationally representative Health and Retirement Study. The sample consisted of 2,688 persons: 1,380 who developed DSL during the study and 1,308 who did not. Although participation in each of the productive activities was associated with fewer depressive symptoms for older adults with DSL, volunteering was also the only variable that moderated the relationship between DSL and depressive symptoms. Persons with a DSL who volunteered exhibited a larger decrease in depressive symptoms compared to persons without sensory loss who volunteered. A volunteer intervention for older adults with DSL may be a viable option to help reduce depression in this population.
The Long Arm of Offspring: Adult Children’s Troubles as Teenagers and Elderly Parents’ Mental Health
Authors: Milkie Melissa A. , Norris Dawn R. , Bierman Alex
Published: April 2011

Little research examines the longevity of the influence of children’s problems on parental well-being. Integrating stress process and life-course perspectives, the authors argue that children’s problematic experiences in adolescence have strong capabilities to influence parents’ mental health in late life, decades after these experiences occur. With a sample of 670 African American and White mothers and fathers age 65 and older, the authors show that elderly parents have higher levels of anger when their offspring had more difficulties as teens; for Black parents this association remains with controls for children’s problems as adults and current concerns about adult children, whereas for Whites it is mediated by concerns. Teen difficulties are also related to current depression for elderly Black but not White parents. This research adds to the literature on family, mental health, and aging by showing how psychological well-being in late life is in part a function of parenting experiences decades earlier.
Nursing Home Stays and the Pace of Severe Disability Onset
Authors: Latham Kenzie
Published: April 2011

Severe disability is an important predictor of nursing home admissions. The purpose of this study is to examine the role of severe disability pacing on risk of short- and long-term nursing home stays. Respondents who developed severe disability were assigned into one of two pacing trajectories: catastrophic or progressive disability. The author analyzed seven waves of data from the Health and Retirement Study and created a series of discrete-time event history models. The analysis showed that the risk associated with severe disability and nursing home stays varied based on severe disability pacing. Progressive and catastrophic disability were associated with increased risk of short- and long-term stays; however, the risk of nursing home stays was much greater for respondents with catastrophic disability for short- and long-term stays. The findings have implications for policy and research. The author suggests that future research focus on interventions aimed at slowing the pace of severe disability.
Evaluation of an interprofessional practice placement in a UK in-patient palliative care unit
Authors: Dando Nicholas , d’Avray Lynda , Colman Jane , Hoy Andrew , Todd Jennifer
Published: April 2011

This paper reports on undergraduate students’ evaluation of a new hospice-based interprofessional practice placement (IPP) that took place in the voluntary sector from 2008 to 2009. Ward-based interprofessional training has been successfully demonstrated in a range of clinical environments. However, the multidisciplinary setting within a hospice in-patient unit offered a new opportunity for interprofessional learning. The development and delivery of the IPP initiative is described, whereby multidisciplinary groups of 12 students provided hands-on care for a selected group of patients, under the supervision of trained health care professionals. The placement was positively evaluated and students reported an increased understanding of both their own role and that of other professionals in the team. The evaluation also suggests that additional learning opportunities were provided by the in-patient palliative care unit. The results of this evaluation suggest that the in-patient unit of a hospice caring for patients with life-limiting illness provides a suitable environment to demonstrate and learn about interprofessional practice.
Illicit drug use as a challenge to the delivery of end-of-life care services to homeless persons: Perceptions of health and social services professionals
Authors: McNeil Ryan , Guirguis-Younger Manal
Published: April 2011

Homeless persons tend to die younger than the housed population and have complex, often unmet, end-of-life care needs. High levels of illicit drug use among this population are a particular challenge for health and social services professionals involved in end-of-life care services delivery. This article explores the challenges of end-of-life care services to homeless illicit drug users based on data collected during a national study on end-of-life care services delivery to homeless persons in Canada. The authors conducted qualitative interviews with 50 health and social services professionals involved in health services delivery to homeless persons in five cities. Interviews were transcribed verbatim and analysed thematically. Themes were organised into two domains. First, barriers preventing homeless illicit drug users from accessing end-of-life care services, such as competing priorities (e.g. withdrawal management), lack of trust in healthcare providers and discrimination. Second, challenges to end-of-life care services delivery to this population in health and social care settings, including non-disclosure of illicit drug use, pain and symptom management, interruptions in care, and lack of experience with addictions. The authors identify a need for increased research on the role of harm reduction in end-of-life care settings to address these challenges.
“It’s Not Just a Job. This Is Where We Live. This Is Our Backyard”: The Experiences of Expert Legal and Advocate Providers With Sexually Assaulted Women in Rural Areas
Authors: Annan Sandra L.
Published: April 2011

Sexual assault research has focused almost exclusively on urban areas, and research examining the experiences of expert service providers is nearly nonexistent. The purpose of this study was to add to the understanding of providers’ experiences in working with sexually assaulted women in rural communities. Secondary victimization theory suggests that the nature of postassault expert interventions may have an adverse impact on victims. The focus of this hermeneutic phenomenological study was to explore the lived experiences of providers regarding their interactions with sexual assault survivors living in rural communities. Data were gathered from prosecutors, law enforcement, crisis center advocates, social workers, and victim-witness associates. Data analysis led to the identification of five significant themes: (a) rural-specific confidentiality issues, (b) resource needs in a rural setting, (c) the connection between victim blaming and low levels of reporting, (d) negative provider views of the community, and (e) smaller communities provided better victim care. Psychiatric nurses and mental health care systems have many opportunities to intervene with abused women in inpatient, outpatient, and other community settings. In primary and acute care setting, nurses should assess patients for a history of violence using multiple screening questions and should also educate victims and their families about available resources.
Adolescents’ Experiences With Uxoricide
Authors: Steeves Richard H. , Parker Barbara , Laughon Kathryn , Knopp Andrea , Thompson Mary E.
Published: April 2011

The purpose of this study was to describe the experiences of individuals who survived the loss of one or both parents through parental homicide or homicide/suicide as adolescents. Participants ( N = 34) were aged between 12 and 19 years at the time of the death and were aged between 29 and 64 years at the time of the interview. Participants were interviewed twice and asked to tell the story of their lives. Data were analyzed in the hermeneutic phenomenological tradition using a stepwise process of developing categories and then a single complex theme. Common categories of participants’ childhoods included abuse both before and after the uxoricide and vivid memories of the homicide. As adults, most participants reported difficulties with intimate relationships, legal problems, and substance use. Integrity was an overarching theme for these participants. Among those who had integrated the story of the homicide into their adult lives, some believed that they were doing well whereas others did not. Some participants had isolated the event and considered that they were doing well as a result. These findings are limited by the convenience sample but offer a rich portrait of the lives of individuals who experienced uxoricide as adolescents. Clinicians might be advised to tread carefully if individuals report that they have isolated rather than integrated the uxoricide into their adult lives. No evidence exists in support that either stance is preferable.
Queering the birthing space: Phenomenological interpretations of the relationships between lesbian couples and perinatal nurses in the context of birthing care
Authors: Goldberg Lisa , Harbin Ami , Campbell Sue
Published: April 2011

As health care institutions continue to promote diversity initiatives within the context of Family-Centered and Woman-Centered Care, the taken-for-grantedness of heteronormativity and homophobia remain pervasive in health care practices, including those of perinatal nurses, to the extent that nurses’ relationships with lesbian birthing couples are often thwarted. Attending to the complexities of queer (lesbian) orientations embedded in the philosophical tenets of feminist and queer phenomenology, this article draws upon experiential findings derived from interview data to understand lesbian couples’ relationships with perinatal nurses in the context of birthing care in eastern Canada.
Computational Assessment of Text Legibility in Lecture Halls
Authors: Hongyi Cai  , Kim Jong-Jin , Green Paul A.
Published: April 2011

Text presented in lecture halls often simultaneously appears on multiple visual displays (e.g., blackboards, projection screens, video monitors), which should be legible to the entire audience seated in an ideal viewing area. Existing guidelines identify this area as fan-shaped, but the origin of those guidelines and the data on which they are based are not specified. To supplement the guidelines, this paper describes the development of a computer program (available online) to compute locations in which all displays are legible to the audience, which considers the height, width, location and orientation of each display, text geometries (height, height-to-stroke width ratio) and its lighting conditions (background luminance, luminance contrast percent), as well as the observer’s visual acuity. This program was validated in a small experiment involving 21 subjects looking at text in a lecture hall, and further examined for two other test cases.
B-type natriuretic peptide as an independent predictor of coronary disease extension in non-ST elevation coronary syndromes with preserved systolic function
Authors: Palazzuoli Alberto , Caputo Maria , Fineschi Massimo , Navarri Romina , Calabrò Anna , Cameli Matteo , Campagna Maria Stella , Franci Beatrice , Pierli Carlo , Nuti Ranuccio , Maisel Alan
Published: April 2011

Objective: B-type natriuretic peptide (BNP) has been employed as a risk marker in patients with coronary artery disease (CAD) with ST elevation and non-ST elevation. It is not yet established if early BNP measurements provide additional information to troponin and electrocardiographic analysis in patients without ventricular enlargement and systolic dysfunction. Design: This study compared BNP levels in patients with stable angina (SA) and acute coronary syndromes with non-ST elevation in relation to angiographic lesions (NSTEMI-ACS). Moreover, the diagnostic utility of BNP was determined using the receiver operating characteristic curve. Patients: 280 patients with CAD without ST elevation and preserved systolic function were studied. BNP samples were measured in all recruited patients within 24 hours of hospitalization. Results: BNP values increased progressively with the severity of diagnosis: SA ( n = 85; 50.4 ± 50 pg/ml) NSTEMI-ACS ( n = 195; 283 ± 269 pg/ml; p < 0.0001). The analysis of BNP in relation to the number of involved vessels demonstrated significantly increased levels in patients with multivessel disease compared to patients with 1- or 2-vessel disease ( p < 0.001 and p < 0.003). Values of BNP >80 pg/ml were shown to be able to predict CAD severity and coronary vessel involvement (AUC = 0.80; p = 0.0001) with a sensitivity of 78% and a specificity of 72%. In multivariate analysis, BNP levels >80 pg/ml, CAD history, and ST deviation >2 mm were confirmed as independent predictors of CAD severity. Conclusions: Circulating BNP levels appear elevated in NSTEMI-ACS, without left ventricular systolic dysfunction. A BNP cut-off value of 80 pg/ml is a good predictor of CAD extension.
Induction of human fetal hemoglobin via the NRF2 antioxidant response signaling pathway
Authors: Macari Elizabeth R. , Lowrey Christopher H.
Published: April 2011

Although hematopoietic stem cell transplantation and gene therapy have the potential to cure β-thalassemia and sickle cell disease, they are not currently available to most people with these diseases. In the near term, pharmacologic induction of fetal hemoglobin (HbF) may offer the best possibility for safe, effective, and widely available therapy. In an effort to define new pathways for targeted drug development for HbF induction, we evaluated the nuclear factor erythroid 2–related factor 2 (NRF2) antioxidant response element signaling pathway. We found that 3 well-known activators of this pathway increased γ-globin mRNA at nontoxic doses in K562 cells. Tert-butylhydroquinone (tBHQ), the most active of these compounds, increased cellular levels and nuclear translocation of NRF2 and binding of NRF2 to the γ-globin promoter. siRNA knockdown of NRF2 inhibited γ-globin induction by tBHQ. When tested in human primary erythroid cells, tBHQ induced NRF2 binding to the γ-globin promoter, increased γ-globin mRNA and HbF, and suppressed β-globin mRNA and HbA, resulting in a > 3-fold increase in the percentage of HbF. These results suggest that drugs that activate the NRF2/antioxidant response element signaling pathway have the potential to induce therapeutic levels of HbF in people with β-hemoglobinopathies.
Comparative proteomic analysis of Lactobacillus plantarumfor the identification of key proteins in bile tolerance
Authors: Hamon Erwann , Horvatovich Peter , Izquierdo Esther , Bringel Françoise , Marchioni Eric , Aoudé-Werner Dalal , Ennahar Saïd
Published: April 2011

Background

Lactic acid bacteria are commonly marketed as probiotics based on their putative or proven health-promoting effects. These effects are known to be strain specific but the underlying molecular mechanisms remain poorly understood. Therefore, unravelling the determinants behind probiotic features is of particular interest since it would help select strains that stand the best chance of success in clinical trials. Bile tolerance is one of the most crucial properties as it determines the ability of bacteria to survive in the small intestine, and consequently their capacity to play their functional role as probiotics. In this context, the objective of this study was to investigate the natural protein diversity within the Lactobacillus plantarum species with relation to bile tolerance, using comparative proteomics.

Results

Bile tolerance properties of nine L. plantarum strains were studied in vitro. Three of them presenting different bile tolerance levels were selected for comparative proteomic analysis: L. plantarum 299 V (resistant), L. plantarum LC 804 (intermediate) and L. plantarum LC 56 (sensitive). Qualitative and quantitative differences in proteomes were analyzed using two-dimensional electrophoresis (2-DE), tryptic digestion, liquid chromatography-mass spectrometry analysis and database search for protein identification. Among the proteins correlated with differences in the 2-DE patterns of the bacterial strains, 15 have previously been reported to be involved in bile tolerance processes. The effect of a bile exposure on these patterns was investigated, which led to the identification of six proteins that may be key in the bile salt response and adaptation in L. plantarum: two glutathione reductases involved in protection against oxidative injury caused by bile salts, a cyclopropane-fatty-acyl-phospholipid synthase implicated in maintenance of cell envelope integrity, a bile salt hydrolase, an ABC transporter and a F0F1-ATP synthase which participate in the active removal of bile-related stress factors.

Conclusions

These results showed that comparative proteomic analysis can help understand the differential bacterial properties of lactobacilli. In the field of probiotic studies, characteristic proteomic profiles can be identified for individual properties that may serve as bacterial biomarkers for the preliminary selection of strains with the best probiotic potential.
The novel curcumin analog FLLL32 decreases STAT3 DNA binding activity and expression, and induces apoptosis in osteosarcoma cell lines
Authors: Fossey Stacey L , Bear Misty D , Lin Jiayuh , Li Chenglong , Schwartz Eric B , Li Pui-Kai , Fuchs James R , Fenger Joelle , Kisseberth William C , London Cheryl A
Published: April 2011

Background

Curcumin is a naturally occurring phenolic compound shown to have a wide variety of antitumor activities; however, it does not attain sufficient blood levels to do so when ingested. Using structure-based design, a novel compound, FLLL32, was generated from curcumin. FLLL32 possesses superior biochemical properties and more specifically targets STAT3, a transcription factor important in tumor cell survival, proliferation, metastasis, and chemotherapy resistance. In our previous work, we found that several canine and human osteosarcoma (OSA) cell lines, but not normal osteoblasts, exhibit constitutive phosphorylation of STAT3. Compared to curcumin, we hypothesized that FLLL32 would be more efficient at inhibiting STAT3 function in OSA cells and that this would result in enhanced downregulation of STAT3 transcriptional targets and subsequent death of OSA cells.

Methods

Human and canine OSA cells were treated with vehicle, curcumin, or FLLL32 and the effects on proliferation (CyQUANT®), apoptosis (SensoLyte® Homogeneous AMC Caspase- 3/7 Assay kit, western blotting), STAT3 DNA binding (EMSA), and vascular endothelial growth factor (VEGF), survivin, and matrix metalloproteinase-2 (MMP2) expression (RT-PCR, western blotting) were measured. STAT3 expression was measured by RT-PCR, qRT- PCR, and western blotting.

Results

Our data showed that FLLL32 decreased STAT3 DNA binding by EMSA. FLLL32 promoted loss of cell proliferation at lower concentrations than curcumin leading to caspase-3- dependent apoptosis, as evidenced by PARP cleavage and increased caspase 3/7 activity; this could be inhibited by treatment with the pan-caspase inhibitor Z-VAD-FMK. Treatment of OSA cells with FLLL32 decreased expression of survivin, VEGF, and MMP2 at both mRNA and protein levels with concurrent decreases in phosphorylated and total STAT3; this loss of total STAT3 occurred, in part, via the ubiquitin-proteasome pathway.

Conclusions

These data demonstrate that the novel curcumin analog FLLL32 has biologic activity against OSA cell lines through inhibition of STAT3 function and expression. Future work with FLLL32 will define the therapeutic potential of this compound in vivo.
Sociodemographic and occupational risk factors associated with the development of different burnout types: the cross-sectional University of Zaragoza study
Authors: Montero-Marín Jesús , García-Campayo Javier , Fajó-Pascual Marta , Carrasco José Miguel , Gascón Santiago , Gili Margarita , Mayoral-Cleries Fermín
Published: April 2011

Background

Three different burnout types have been described: The "frenetic" type describes involved and ambitious subjects who sacrifice their health and personal lives for their jobs; the "underchallenged" type describes indifferent and bored workers who fail to find personal development in their jobs and the "worn-out" in type describes neglectful subjects who feel they have little control over results and whose efforts go unacknowledged. The study aimed to describe the possible associations between burnout types and general sociodemographic and occupational characteristics.

Methods

A cross-sectional study was carried out on a multi-occupational sample of randomly selected university employees (n = 409). The presence of burnout types was assessed by means of the "Burnout Clinical Subtype Questionnaire (BCSQ-36)", and the degree of association between variables was assessed using an adjusted odds ratio (OR) obtained from multivariate logistic regression models.

Results

Individuals working more than 40 hours per week presented with the greatest risk for "frenetic" burnout compared to those working fewer than 35 hours (adjusted OR = 5.69; 95% CI = 2.52-12.82;p< 0.001). Administration and service personnel presented the greatest risk of "underchallenged" burnout compared to teaching and research staff (adjusted OR = 2.85; 95% CI = 1.16-7.01;p= 0.023). Employees with more than sixteen years of service in the organisation presented the greatest risk of "worn-out" burnout compared to those with less than four years of service (adjusted OR = 4.56; 95% CI = 1.47-14.16;p= 0.009).

Conclusions

This study is the first to our knowledge that suggests the existence of associations between the different burnout subtypes (classified according to the degree of dedication to work) and the different sociodemographic and occupational characteristics that are congruent with the definition of each of the subtypes. These results are consistent with the clinical profile definitions of burnout syndrome. In addition, they assist the recognition of distinct profiles and reinforce the idea of differential characterisation of the syndrome for more effective treatment.
A study protocol for the evaluation of occupational mutagenic/carcinogenic risks in subjects exposed to antineoplastic drugs: a multicentric project
Authors: Moretti Massimo , Bonfiglioli Roberta , Feretti Donatella , Pavanello Sofia , Mussi Francesca , Grollino Maria G , Villarini Milena , Barbieri Anna , Ceretti Elisabetta , Carrieri Mariella , Buschini Annamaria , Appolloni Massimo , Dominici Luca , Sabatini Laura , Gelatti Umberto , Bartolucci Giovanni B , Poli Paola , Stronati Laura , Mastrangelo Giuseppe , Monarca Silvano
Published: April 2011

Background

Some industrial hygiene studies have assessed occupational exposure to antineoplastic drugs; other epidemiological investigations have detected various toxicological effects in exposure groups labeled with the job title. In no research has the same population been studied both environmentally and epidemiologically. The protocol of the epidemiological study presented here uses an integrated environmental and biological monitoring approach. The aim is to assess in hospital nurses preparing and/or administering therapy to cancer patients the current level of occupational exposure to antineoplastic drugs, DNA and chromosome damage as cancer predictive effects, and the association between the two.

Methods/Design

About 80 healthy non-smoking female nurses, who job it is to prepare or handle antineoplastic drugs, and a reference group of about 80 healthy non-smoking female nurses not occupationally exposed to chemicals will be examined simultaneously in a cross-sectional study. All the workers will be recruited from five hospitals in northern and central Italy after their informed consent has been obtained.

Evaluation of surface contamination and dermal exposure to antineoplastic drugs will be assessed by determining cyclophosphamide on selected surfaces (wipes) and on the exposed nurses' clothes (pads). The concentration of unmetabolized cyclophosphamide as a biomarker of internal dose will be measured in end-shift urine samples from exposed nurses.

Biomarkers of effect and susceptibility will be assessed in exposed and unexposed nurses: urinary concentration of 8-hydroxy-2-deoxyguanosine; DNA damage detected using the single-cell microgel electrophoresis (comet) assay in peripheral white blood cells; micronuclei and chromosome aberrations in peripheral blood lymphocytes. Genetic polymorphisms for enzymes involved in metabolic detoxification (i.e. glutathione S-transferases) will also be analysed.

Using standardized questionnaires, occupational exposure will be determined in exposed nurses only, whereas potential confounders (medicine consumption, lifestyle habits, diet and other non-occupational exposures) will be assessed in both groups of hospital workers.

Statistical analysis will be performed to ascertain the association between occupational exposure to antineoplastic drugs and biomarkers of DNA and chromosome damage, after taking into account the effects of individual genetic susceptibility, and the presence of confounding exposures.

Discussion

The findings of the study will be useful in updating prevention procedures for handling antineoplastic drugs.
Systems analysis of endothelial cell plasma membrane proteome of rat lung microvasculature
Authors: Li Yan , Massey Kerri , Witkiewicz Halina , Schnitzer Jan E
Published: April 2011

Background

Endothelial cells line all blood vessels to form the blood-tissue interface which is critical for maintaining organ homeostasis and facilitates molecular exchange. We recently used tissue subcellular fractionation combined with several multi-dimensional mass spectrometry-based techniques to enhance identification of lipid-embedded proteins for large-scale proteomic mapping of luminal endothelial cell plasma membranes isolated directly from rat lungs in vivo. The biological processes and functions of the proteins expressed at this important blood-tissue interface remain unexplored at a large scale.

Results

We performed an unbiased systems analysis of the endothelial cell surface proteome containing over 1800 proteins to unravel the major functions and pathways apparent at this interface. As expected, many key functions of plasma membranes in general (i.e., cell surface signaling pathways, cytoskeletal organization, adhesion, membrane trafficking, metabolism, mechanotransduction, membrane fusion, and vesicle-mediated transport) and endothelial cells in particular (i.e., blood vessel development and maturation, angiogenesis, regulation of endothelial cell proliferation, protease activity, and endocytosis) were significantly overrepresented in this proteome. We found that endothelial cells express multiple proteins that mediate processes previously reported to be restricted to neuronal cells, such as neuronal survival and plasticity, axon growth and regeneration, synaptic vesicle trafficking and neurotransmitter metabolic process. Surprisingly, molecular machinery for protein synthesis was also detected as overrepresented, suggesting that endothelial cells, like neurons, can synthesize proteins locally at the cell surface.

Conclusion

Our unbiased systems analysis has led to the potential discovery of unexpected functions in normal endothelium. The discovery of the existence of protein synthesis at the plasma membrane in endothelial cells provides new insight into the blood-tissue interface and endothelial cell surface biology.
Nanostructured titania films sensitized by quantum dot chalcogenides
Authors: Kontos Athanassios G , Likodimos Vlassis , Vassalou Eleni , Kapogianni Ioanna , Raptis Yannis S , Raptis Costas , Falaras Polycarpos
Published: April 2011

The optical and structural properties of cadmium and lead sulfide nanocrystals deposited on mesoporous TiO2 substrates via the successive ionic layer adsorption and reaction method were comparatively investigated by reflectance, transmittance, micro-Raman and photoluminescence measurements. Enhanced interfacial electron transfer is evidenced upon direct growth of both CdS and PbS on TiO2 through the marked quenching of their excitonic emission. The optical absorbance of CdS/TiO2 can be tuned over a narrow spectral range. On the other side PbS/TiO2 exhibits a remarkable band gap tunability extending from the visible to the near infrared range, due to the distinct quantum size effects of PbS quantum dots. However, PbS/TiO2 suffers from severe degradation upon air exposure. Degradation effects are much less pronounced for CdS/TiO2 that is appreciably more stable, though it degrades readily upon visible light illumination.
Atomic scale investigation of silicon nanowires and nanoclusters
Authors: Roussel Manuel , Chen Wanghua , Talbot Etienne , Lardé Rodrigue , Cadel Emmanuel , Gourbilleau Fabrice , Grandidier Bruno , Stiévenard Didier , Pareige Philippe
Published: April 2011

In this study, we have performed nanoscale characterization of Si-clusters and Si-nanowires with a laser-assisted tomographic atom probe. Intrinsic and p-type silicon nanowires (SiNWs) are elaborated by chemical vapor deposition method using gold as catalyst, silane as silicon precursor, and diborane as dopant reactant. The concentration and distribution of impurity (gold) and dopant (boron) in SiNW are investigated and discussed. Silicon nanoclusters are produced by thermal annealing of silicon-rich silicon oxide and silica multilayers. In this process, atom probe tomography (APT) provides accurate information on the silicon nanoparticles and the chemistry of the nanolayers.
No evidence of XMRV in prostate cancer cohorts in the Midwestern United States
Authors: Sakuma Toshie , Hué Stéphane , Squillace Karen A , Tonne Jason M , Blackburn Patrick R , Ohmine Seiga , Thatava Tayaramma , Towers Greg J , Ikeda Yasuhiro
Published: April 2011

Background

Xenotropic murine leukemia virus (MLV)-related virus (XMRV) was initially identified in prostate cancer (PCa) tissue, particularly in the prostatic stromal fibroblasts, of patients homozygous for the RNASEL R462Q mutation. A subsequent study reported XMRV antigens in malignant prostatic epithelium and association of XMRV infection with PCa, especially higher-grade tumors, independently of the RNASEL polymorphism. Further studies showed high prevalence of XMRV or related MLV sequences in chronic fatigue syndrome patients (CFS), while others found no, or low, prevalence of XMRV in a variety of diseases including PCa or CFS. Thus, the etiological link between XMRV and human disease remains elusive. To address the association between XMRV infection and PCa, we have tested prostate tissues and human sera for the presence of viral DNA, viral antigens and anti-XMRV antibodies.

Results

Real-time PCR analysis of 110 PCa (Gleason scores >4) and 40 benign and normal prostate tissues identified six positive samples (5 PCa and 1 non-PCa). No statistical link was observed between the presence of proviral DNA and PCa, PCa grades, and the RNASEL R462Q mutation. The amplified viral sequences were distantly related to XMRV, but nearly identical to endogenous MLV sequences in mice. The PCR positive samples were also positive for mouse mitochondrial DNA by nested PCR, suggesting contamination of the samples with mouse DNA. Immuno-histochemistry (IHC) with an anti-XMRV antibody, but not an anti-MLV antibody that recognizes XMRV, sporadically identified antigen-positive cells in prostatic epithelium, irrespectively of the status of viral DNA detection. No serum (159 PCa and 201 age-matched controls) showed strong neutralization of XMRV infection at 1:10 dilution.

Conclusion

The lack of XMRV sequences or strong anti-XMRV neutralizing antibodies indicates no or very low prevalence of XMRV in our cohorts. We conclude that real-time PCR- and IHC-positive samples were due to laboratory contamination and non-specific immune reactions, respectively.