bluuebunny/crossref_metadata_2025 huggingface dataset:
Sociocultural and linguistic boundaries influencing intercultural communication between nurses and Moroccan patients in southern Spain: a focused ethnography
Authors: Plaza del Pino Fernando J , Soriano Encarnación , Higginbottom Gina MA
Published: May 2013

Background

During the last 25 years, cultural diversity has increased substantially with global migration. In more recent years this has become highly evident in the south of Spain with its steadily increasing Moroccan population. The accompanying differences in ethnocultural values and traditions between the host and newcomer populations may greatly impact healthcare interactions and thus also effective provision of care. This landscape provides for excellent exploration of intercultural communication in healthcare settings and elucidation of possible ways to overcome existing barriers to provision of culturally competent care by nurses. This study aimed to ascertain how nurses perceive their intercultural communication with Moroccan patients and what barriers are evident which may be preventing effective communication and care.

Methods

A focused ethnography was conducted with semi-structured interviews of 32 nurses in three public hospitals in southern Spain. Interviews were audio-recorded and transcribed verbatim before undergoing translation and back-translation between Spanish and English. Data was managed, classified and ordered with the aid of AQUAD.6 (Günter L. Huber, Tübingen, Germany) qualitative data analysis software.

Results

As an important dimension of cultural competence, findings from the interviews with nurses in this study were interpreted within the framework of intercultural communication. Various barriers, for which we have termed “boundaries”, seem to exist preventing effective communication between nurses and their patients. The substantial language barrier seems to negatively affect communication. Relations between the nurses and their Moroccan patients are also marked by prejudices and social stereotypes which likely compromise the provision of culturally appropriate care.

Conclusions

The language barrier may compromise nursing care delivery and could be readily overcome by implementation of professional interpretation within the hospital settings. Moreover, it is essential that the nurses of southern Spain are educated in the provision of culturally appropriate and sensitive care.
Blockade of PI3K/AKT pathway enhances sensitivity of Raji cells to chemotherapy through down-regulation of HSP70
Authors: Fang Xiaosheng , Jiang Yujie , Feng Lili , Chen Haiping , Zhen Changqing , Ding Mei , Wang Xin
Published: May 2013

Up-regulation of heat shock protein 70 (HSP70) could be elicited primarily by heat in former studies, and this was proved to be associated with cancer progression. Burkitt's lymphoma is one of highly aggressive B-cell non-Hodgkin’s lymphoma and is one of the fastest growing human tumors. To investigate the effect of HSP70 expression on the sensitivity of human Burkitt lymphoma cells (Raji cells) to chemotherapy and its role in the involvement of PI3K/AKT pathway, we evaluated the effects of LY294002, a PI3K inhibitor, on the expression of HSP70 and cell sensitivity to adriamycin (ADM) or cisplatin (DDP). In present study, expressions of HSP70, AKT and phosphorylated AKT (p-AKT) in Raji cells were measured by Western-Blot. Apoptosis index of Raji cells was examined by flow cytometry. Cytotoxicities of adriamycin (ADM) and cisplatin (DDP) were determined by WST-8 assay. We found that hyperthermia (42 degrees for 1 hour) up-regulated the expression of HSP70 expression and blockade of PI3K/AKT pathway down-regulated HSP70 expression in Raji cells. Compared to cells treated with ADM or DDP alone, hyperthermia protected cells from chemotherapy while LY294002 enhanced sensitivity of Raji cells to chemotherapy. Our results suggested down-regulation of HSP70 expression by blockade of PI3K/AKT pathway maybe responsible for the increased sensitivity of Raji cells to chemotherapy. Targeting PI3K/AKT pathway or inhibiting HSP70 expression may be beneficial for chemotherapy treatment of Burkitt lymphoma patients.
Iodine and doxorubicin, a good combination for mammary cancer treatment: antineoplastic adjuvancy, chemoresistance inhibition, and cardioprotection
Authors: Alfaro Yunuen , Delgado Guadalupe , Cárabez Alfonso , Anguiano Brenda , Aceves Carmen
Published: May 2013

Background

Although mammary cancer (MC) is the most common malignant neoplasia in women, the mortality for this cancer has decreased principally because of early detection and the use of neoadjuvant chemotherapy. Of several preparations that cause MC regression, doxorubicin (DOX) is the most active, first-line monotherapeutic. Nevertheless, its use is limited due to the rapid development of chemoresistance and to the cardiotoxicity caused by free radicals. In previous studies we have shown that supplementation with molecular iodine (I2) has a powerful antineoplastic effect in methylnitrosourea (MNU)-induced experimental models of MC. These studies also showed a consistent antioxidant effect of I2 in normal and tumoral tissues.

Methods

Here, we analyzed the effect of I2 in combination with DOX treatment in female Sprague Dawley rats with MNU-induced MC. In the first experiment (short) animals were treated with the therapeutic DOX dose (16 mg/kg) or with lower doses (8 and 4 mg/Kg), in each case with and without 0.05% I2 in drinking water. Iodine treatment began on day 0, a single dose of DOX was injected (ip) on day 2, and the analysis was carried out on day 7. In the second experiment (long) animals with and without iodine supplement were treated with one or two injections of 4 mg/kg DOX (on days 0 and 14) and were analyzed on day 56.

Results

At all DOX doses, the short I2 treatment induced adjuvant antineoplastic effects (decreased tumor size and proliferating cell nuclear antigen level) with significant protection against body weight loss and cardiotoxicity (creatine kinase MB, cardiac lipoperoxidation, and heart damage). With long-term I2, mammary tumor tissue became more sensitive to DOX, since a single injection of the lowest dose of DOX (4 mg/Kg) was enough to stop tumor progression and a second DOX4 injection on day 14 caused a significant and rapid decrease in tumor size, decreased the expression of chemoresistance markers (Bcl2 and survivin), and increased the expression of the apoptotic protein Bax and peroxisome proliferator-activated receptor type gamma.

Conclusions

The DOX-I2 combination exerts antineoplastic, chemosensitivity, and cardioprotective effects and could be a promising strategy against breast cancer progression.
Policymakers’ and other stakeholders’ perceptions of key considerations for health system decisions and the presentation of evidence to inform those considerations: an international survey
Authors: Vogel Joshua P , Oxman Andrew D , Glenton Claire , Rosenbaum Sarah , Lewin Simon , Gülmezoglu A Metin , Souza João Paulo
Published: May 2013

Background

The DECIDE framework was developed to support evidence-informed health system decisions through evidence summaries tailored to health policymakers. The objective of this study was to determine policymakers’ perceptions regarding the criteria in the DECIDE framework and how best to summarise and present evidence to support health system decisions.

Methods

We conducted an online survey of a diverse group of stakeholders with health system decision experience from 15 countries and the World Health Organization. We asked about perceptions of criteria relevant to making health system decisions, use of evidence, grading systems, and evidence summaries.

Results

We received 112 responses (70% response rate). Most respondents had healthcare (85%) and research (79%) experience. They (99%) indicated that systematic consideration of the available evidence would help to improve health system decision-making processes and supported the use of evidence from other countries (94%) and grading systems (81%). All ten criteria in the DECIDE framework were rated as important in the decision-making process. Respondents had divergent views regarding whether the same (38%) or different (45%) grading systems should be used across different types of health decisions. All components of our evidence summary were rated as important by over 90% of respondents.

Conclusions

Survey respondents were supportive of the DECIDE framework for health system decisions and the use of succinct summaries of the estimated size of effects and the quality of evidence. It is uncertain whether the findings of this survey represent the views of policymakers with little or no healthcare and research experience.
Pattern of activation of human antigen presenting cells by genotype GII.4 norovirus virus-like particles
Authors: Ponterio Eleonora , Petrizzo Annacarmen , Di Bartolo Ilaria , Buonaguro Franco Maria , Buonaguro Luigi , Ruggeri Franco Maria
Published: May 2013

Background

Virus-like particles (VLPs) from an Italian GII.4 norovirus strain were used to investigate activation and maturation of circulating antigen presenting cells (APCs) of human origin.

Methods

Peripheral blood mononuclear cells (PBMCs) isolated from five healthy subjects were pulsed ex vivo with VLPs, and stained with a set of monoclonal antibodies (MAbs) for phenotypic analysis by flow cytometry. Cytokine release in cell supernatants was investigated by ELISA.

Results

Norovirus VLPs induced activation and maturation of circulating APCs derived from the five donors, as well as production of IL-6, IFN-γ and TNF-α cytokines.

Conclusions

The present results suggest that VLPs can activate antigen presenting cells for an efficient induction of the adaptive immune response.
Role of warm ischemia on innate and adaptive responses in a preclinical renal auto-transplanted porcine model
Authors: Rossard Ludivine , Favreau Frédéric , Giraud Sebastien , Thuillier Raphael , Le Pape Sylvain , Goujon Jean Michel , Valagier Alexandre , Hauet Thierry
Published: May 2013

Background

Deceased after cardiac arrest donor are an additional source of kidney graft to overcome graft shortage. Deciphering the respective role of renal warm and cold ischemia is of pivotal interest in the transplantation process.

Methods

Using a preclinical pig model of renal auto-transplantation, we investigated the consequences of warm and cold ischemia on early innate and adaptive responses as well as graft outcome. Kidneys were subjected to either 60 min-warm ischemia (WI) or auto-transplanted after cold storage for 24 h at 4°C (CS), or both conditions combined (WI + CS). Renal function, immune response and cytokine expression, oxidative stress and cell death were investigated at 3 h, 3 and 7 days (H3, D3 and D7) after reperfusion. At 3 months, we focused on cell infiltration and tissue remodelling.

Results

WI + CS induced a delayed graft function linked to higher tubular damage. Innate response occurred at D3 associated to a pro-oxidative milieu with a level dependent on the severity of ischemic injury whereas adaptive immune response occurred only at D7 mainly due to CS injuries and aggravated by WI. Graft cellular death was an early event detected at H3 and seems to be one of the first ischemia reperfusion injuries. These early injuries affect graft outcome on renal function, cells infiltration and fibrosis development.

Conclusions

The results indicate that the severe ischemic insult found in kidneys from deceased after cardiac arrest donor affects kidney outcome and promotes an uncontrolled deleterious innate and adaptive response not inhibited 3 months after reperfusion.
Influence of nanoparticles of platinum on chicken embryo development and brain morphology
Authors: Prasek Marta , Sawosz Ewa , Jaworski Slawomir , Grodzik Marta , Ostaszewska Teresa , Kamaszewski Maciej , Wierzbicki Mateusz , Chwalibog Andre
Published: May 2013

Platinum nanoparticles (NP-Pt) are noble metal nanoparticles with unique physiochemical properties that have recently elicited much interest in medical research. However, we still know little about their toxicity and influence on general health. We investigated effects of NP-Pt on the growth and development of the chicken embryo model with emphasis on brain tissue micro- and ultrastructure. The embryos were administered solutions of NP-Pt injected in ovo at concentrations from 1 to 20 μg/ml. The results demonstrate that NP-Pt did not affect the growth and development of the embryos; however, they induced apoptosis and decreased the number of proliferating cells in the brain tissue. These preliminary results indicate that properties of NP-Pt might be utilized in brain cancer therapy, but potential toxic side effects must be elucidated in extensive follow-up research.
Existence of homoclinic orbits for a class of p-Laplacian systems in a weighted Sobolev space
Authors: Shi Xiubo , Zhang Qiongfen , Zhang Qi-Ming
Published: May 2013

By applying the mountain pass theorem and symmetric mountain pass theorem in critical point theory, the existence of at least one or infinitely many homoclinic solutions is obtained for the following p-Laplacian system:

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The frantic play of the concealed HIV envelope cytoplasmic tail
Authors: Santos da Silva Eveline , Mulinge Martin , Perez Bercoff Danielle
Published: May 2013

Lentiviruses have unusually long envelope (Env) cytoplasmic tails, longer than those of other retroviruses. Whereas the Env ectodomain has received much attention, the gp41 cytoplasmic tail (gp41-CT) is one of the least studied parts of the virus. It displays relatively high conservation compared to the rest of Env. It has been long established that the gp41-CT interacts with the Gag precursor protein to ensure Env incorporation into the virion. The gp41-CT contains distinct motifs and domains that mediate both intensive Env intracellular trafficking and interactions with numerous cellular and viral proteins, optimizing viral infectivity. Although they are not fully understood, a multiplicity of interactions between the gp41-CT and cellular factors have been described over the last decade; these interactions illustrate how Env expression and incorporation into virions is a finely tuned process that has evolved to best exploit the host system with minimized genetic information. This review addresses the structure and topology of the gp41-CT of lentiviruses (mainly HIV and SIV), their domains and believed functions. It also considers the cellular and viral proteins that have been described to interact with the gp41-CT, with a particular focus on subtype-related polymorphisms.
Molecular investigation of Torque teno sus virus in geographically distinct porcine breeding herds of Sichuan, China
Authors: Mei Miao , Zhu Ling , Xu Zhiwen , Zhao Ling , Zhou Yuancheng , Wu Yunfei , Li Song , Wei Haoche , Guo Wanzhu
Published: May 2013

Background

Torque teno sus virus (TTSuV), infecting domestic swine and wild boar, is a non-enveloped virus with a circular, single-stranded DNA genome. which has been classified into the genera Iotatorquevirus (TTSuV1) and Kappatorquevirus (TTSuV2) of the family Anelloviridae. A molecular study was conducted to detect evidence of a phylogenic relationship between these two porcine TTSuV genogroups from the sera of 244 infected pigs located in 21 subordinate prefectures and/or cities of Sichuan.

Results

Both genogroups of TTSuV were detected in pig sera collected from all 21 regions examined. Of the 244 samples, virus from either genogroup was detected in 203 (83.2%), while 44 animals (18.0%) were co-infected with viruses of both genogroups. Moreover, TTSuV2 (186/244, 76.2%) was more prevalent than TTSuV1 (61/244, 25%). There was statistically significant difference between the prevalence of genogroups 1 infection alone (9.4%, 23/244) and 2 alone (64.8%, 158/244), and between the prevalence of genogroups 2 (76.2%, 186/244) and both genogroups co-infection (18.0%, 44/244). The untranslated region of the swine TTSuV genome was found to be an adequate molecular marker of the virus for detection and surveillance. Phylogenetic analysis indicated that both genogroups 1 and 2 could be further divided into two subtypes, subtype a and b. TTSuV1 subtype b and the two TTSuV2 subtypes are more prevalent in Sichuan Province.

Conclusions

Our study presents detailed geographical evidence of TTSuV infection in China.
Expression of the epithelial-mesenchymal transition-related proteins and their clinical significance in lung adenocarcinoma
Authors: Shi Yongli , Wu Hongyan , Zhang Mingyi , Ding Lei , Meng Fanqing , Fan Xiangshan
Published: May 2013

Background

Epithelial-mesenchymal transition (EMT) is defined as switching of polarized epithelial cells to a migratory fibroblastoid phenotype. EMT is known to be involved in the progression and metastasis of various cancers. The aim was to evaluate that whether EMT-related proteins' alterations are associated with clinicopathological features and prognosis in lung adenocarcinoma.

Methods

The expression of EMT-related proteins including cytokeratin, E-cadherin, TTF-1, β-catenin, vimentin, Snail, Twist, CD44 was evaluated by immunohistochemistry using a tissue array method in the lung adenocarcinoma tissues of 95 patients. In addition, clinicopathological characteristics and survival were compared with the expression of EMT-related proteins.

Results

Loss of epithelial proteins and/or acquisition of the expression of mesenchymal proteins were observed in lung adenocarcinoma. These proteins’ alteration was associated with poor cell differentiation and poor patients’ outcome, respectively. Subjects were divided into two groups according to the number of EMT-related proteins’ alteration. A higher number of EMT-related proteins’ alteration was found to be significantly associated with unfavorable outcome. Multivariate analysis showed that a higher number of EMT-related proteins’ alteration was independently associated with poor prognosis.

Conclusions

The number of EMT-related proteins’ alteration is a significant prognostic marker to predict overall survival in patients with lung adenocarcinoma. The information generated will be valuable for the prognosis of patients with lung adenocarcinoma.

Virtual slides

The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1007838329872974
Emerging importance of holobionts in evolution and in probiotics
Authors: Singh Yadvir , Ahmad Javed , Musarrat Javed , Ehtesham Nasreen Z , Hasnain Seyed E
Published: May 2013

The existence of microbe free animals or plants in nature is virtually impossible as they and plants have a certain degree of symbiotic association with microbes. This symbiotic association leads to the formation of holobiont (host and its symbionts). This mutual coexistence is not merely at the physical or chemical level but also at the genetic level leading to the emergence of the concept of hologenome (gene pool of host and its associated symbionts). The abundance of symbionts with the associated gene diversity contributes to the fitness of the holobiont under varying environmental conditions. The hologenome theory of evolution considers the dynamic holobiont as a single unit for natural selection and provides a more accommodating view of evolution blending Darwinism and Lamarkism. Additionally, holobionts are providing scientific basis to our understanding of the growing importance of probiotics in human health and in disease management.
Improving accuracy of cell and chromophore concentration measurements using optical density
Authors: Myers John A , Curtis Brandon S , Curtis Wayne R
Published: May 2013

Background

UV–vis spectrophotometric optical density (OD) is the most commonly-used technique for estimating chromophore formation and cell concentration in liquid culture. OD wavelength is often chosen with little thought given to its effect on the quality of the measurement. Analysis of the contributions of absorption and scattering to the measured optical density provides a basis for understanding variability among spectrophotometers and enables a quantitative evaluation of the applicability of the Beer-Lambert law. This provides a rational approach for improving the accuracy of OD measurements used as a proxy for direct dry weight (DW), cell count, and pigment levels.

Results

For pigmented organisms, the choice of OD wavelength presents a tradeoff between the robustness and the sensitivity of the measurement. The OD at a robust wavelength is primarily the result of light scattering and does not vary with culture conditions; whereas, the OD at a sensitive wavelength is additionally dependent on light absorption by the organism’s pigments. Suitably robust and sensitive wavelengths are identified for a wide range of organisms by comparing their spectra to the true absorption spectra of dyes. The relative scattering contribution can be reduced either by measurement at higher OD, or by the addition of bovine serum albumin. Reduction of scattering or correlation with off-peak light attenuation provides for more accurate assessment of chromophore levels within cells. Conversion factors between DW, OD, and colony-forming unit density are tabulated for 17 diverse organisms to illustrate the scope of variability of these correlations. Finally, an inexpensive short pathlength LED-based flow cell is demonstrated for the online monitoring of growth in a bioreactor at culture concentrations greater than 5 grams dry weight per liter which would otherwise require off-line dilutions to obtain non-saturated OD measurements.

Conclusions

OD is most accurate as a time-saving proxy measurement for biomass concentration when light attenuation is dominated by scattering. However, the applicability of OD-based correlations is highly dependent on the measurement specifications (spectrophotometer model and wavelength) and culture conditions (media type; growth stage; culture stress; cell/colony geometry; presence and concentration of secreted compounds). These variations highlight the importance of treating literature conversion factors as rough approximations as opposed to concrete constants. There is an opportunity to optimize measurements of cell pigment levels by considering scattering and absorption-dependent wavelengths of the OD spectrum.
Co-cultivation of Lactobacillus zeae and Veillonella criceti for the production of propionic acid
Authors: Dietz David , Sabra Wael , Zeng An-Ping
Published: May 2013

In this work a defined co-culture of the lactic acid bacterium Lactobacillus zeae and the propionate producer Veillonella criceti has been studied in continuous stirred tank reactor (CSTR) and in a dialysis membrane reactor. It is the first time that this reactor type is used for a defined co-culture fermentation. This reactor allows high mixing rates and working with high cell densities, making it ideal for co-culture investigations. In CSTR experiments the co-culture showed over a broad concentration range an almost linear correlation in consumption and production rates to the supply with complex nutrients. In CSTR and dialysis cultures a strong growth stimulation of L. zeae by V. criceti was shown. In dialysis cultures very high propionate production rates (0.61 g L-1h-1) with final titers up to 28 g L-1 have been realized. This reactor allows an individual, intracellular investigation of the co-culture partners by omic-technologies to provide a better understanding of microbial communities.
Prediction of lung tumor types based on protein attributes by machine learning algorithms
Authors: Hosseinzadeh Faezeh , KayvanJoo Amir Hossein , Ebrahimi Mansuor , Goliaei Bahram
Published: May 2013

Early diagnosis of lung cancers and distinction between the tumor types (Small Cell Lung Cancer (SCLC) and Non-Small Cell Lung Cancer (NSCLC) are very important to increase the survival rate of patients. Herein, we propose a diagnostic system based on sequence-derived structural and physicochemical attributes of proteins that involved in both types of tumors via feature extraction, feature selection and prediction models. 1497 proteins attributes computed and important features selected by 12 attribute weighting models and finally machine learning models consist of seven SVM models, three ANN models and two NB models applied on original database and newly created ones from attribute weighting models; models accuracies calculated through 10-fold cross and wrapper validation (just for SVM algorithms). In line with our previous findings, dipeptide composition, autocorrelation and distribution descriptor were the most important protein features selected by bioinformatics tools. The algorithms performances in lung cancer tumor type prediction increased when they applied on datasets created by attribute weighting models rather than original dataset. Wrapper-Validation performed better than X-Validation; the best cancer type prediction resulted from SVM and SVM Linear models (82%). The best accuracy of ANN gained when Neural Net model applied on SVM dataset (88%). This is the first report suggesting that the combination of protein features and attribute weighting models with machine learning algorithms can be effectively used to predict the type of lung cancer tumors (SCLC and NSCLC).
Black tea, green tea and risk of breast cancer: an update
Authors: Wu Yili , Zhang Dongfeng , Kang Shan
Published: May 2013

Previous meta-analysis indicated conflicting results in case–control versus cohort studies on the association of green tea with breast cancer risk, and conflicting results were also found in case–control versus cohort studies in another meta-analysis on the association of black tea with breast cancer risk. Many studies were published after the previous meta-analysis. Besides, the dose-response relationship of tea consumption with breast cancer risk is unclear. Thus the association of tea consumption with breast cancer risk was assessed incorporating new publications. Summary relative risk (RR) for highest versus lowest level of tea consumption was calculated based on fixed or random effect models. Dose-response relationship was assessed by restricted cubic spline model and multivariate random-effect meta-regression. The combined results from 9 studies suggested no significant association between green tea consumption and breast cancer risk (RR = 0.82, 95% CI = 0.64-1.04). No significant association was found among cohort studies and case-control studies after sensitivity analysis, respectively. A linear but not significant dose-response association was found between green tea consumption and breast cancer risk. The combined results from 25 studies demonstrated no significant association between black tea consumption and breast cancer risk (RR = 0.98, 95% CI = 0.93-1.03), and no significant association was found in subgroup analysis. A linear but not significant dose-response association was found between black tea consumption and breast cancer risk. Based on the current evidence, black tea and green tea might not contribute significantly to breast cancer risk, respectively.
Hydrothermal synthesis and characterization of straw bundle-like lithium sodium disilicate (silinaite) micro-rods
Authors: Alemi Abdolali , Joo Sang Woo , Khademinia Shahin , Dolatyari Mahboubeh , Bakhtiari Akbar , Moradi Hossein , Saeidi Sorayya
Published: May 2013

Highly mono-shaped straw bundle-like silinaite micro-rods have been synthesized using an aqueous mixture of silicic acid, lithium sulfate, and sodium hydroxide under hydrothermal conditions at 180°C. The synthesized materials were characterized by powder X-ray diffraction technique and Fourier transform infrared spectroscopy. The morphologies of the synthesized materials were studied by field emission scanning electron microscopy technique. The synthesized micro-rods are composed of long, fine nanosheets. Electronic absorption and photoluminescence spectra of the synthesized materials were also studied. With increasing reaction time, a blueshift was observed in the UV–vis electronic absorption and emission spectra of the synthesized materials.
Preconditioning diabetic mesenchymal stem cells with myogenic medium increases their ability to repair diabetic heart
Authors: Khan Mohsin , Ali Fatima , Mohsin Sadia , Akhtar Shoaib , Mehmood Azra , Choudhery Mahmood S , Khan Shaheen N , Riazuddin Sheikh
Published: May 2013

Introduction

Mesenchymal stem cells (MSCs) have the potential for treatment of diabetic cardiomyopathy; however, the repair capability of MSCs declines with age and disease. MSCs from diabetic animals exhibit impaired survival, proliferation, and differentiation and therefore require a strategy to improve their function. The aim of the study was to develop a preconditioning strategy to augment the ability of MSCs from diabetes patients to repair the diabetic heart.

Methods

Diabetes was induced in C57BL/6 mice (6 to 8 weeks) with streptozotocin injections (55 mg/kg) for 5 consecutive days. MSCs isolated from diabetic animals were preconditioned with medium from cardiomyocytes exposed to oxidative stress and high glucose (HG/H-CCM).

Results

Gene expression of VEGF, ANG-1, GATA-4, NKx2.5 MEF2c, PCNA, and eNOS was upregulated after preconditioning with HG/H-CCM, as evidenced by reverse transcriptase/polymerase chain reaction (RT-PCR). Concurrently, increased AKT phosphorylation, proliferation, angiogenic ability, and reduced levels of apoptosis were observed in HG/H-CCM-preconditioned diabetic MSCs compared with nontreated controls. HG/H-CCM-preconditioned diabetic-mouse-derived MSCs (dmMSCs) were transplanted in diabetic animals and demonstrated increased homing concomitant with augmented heart function. Gene expression of angiogenic and cardiac markers was significantly upregulated in conjunction with paracrine factors (IGF-1, HGF, SDF-1, FGF-2) and, in addition, reduced fibrosis, apoptosis, and increased angiogenesis was observed in diabetic hearts 4 weeks after transplantation of preconditioned dmMSCs compared with hearts with nontreated diabetic MSCs.

Conclusions

Preconditioning with HG/H-CCM enhances survival, proliferation, and the angiogenic ability of dmMSCs, augmenting their ability to improve function in a diabetic heart.
Global sensitivity analysis for crosswell seismic and neutron-capture measurements in CO2 storage projects
Authors: Chugunov Nikita , Altundas Yusuf Bilgin , Ramakrishnan T. S. , Senel Ozgur
Published: May 2013

Quantification of reservoir uncertainty is an essential part of a monitoring design. A systematic approach that quantitatively links predicted uncertainties in a monitoring program to the underlying reservoir variability is, however, needed. We developed a methodology for quantifying uncertainty in crosswell seismic monitoring combined with neutron-capture logging and applied global sensitivity analysis (GSA) to compute and rank contributions of uncertain reservoir parameters to the predicted uncertainty of the measurements. The workflow is illustrated by a numerical study using a simplified model of a [Formula: see text] storage site where crosswell measurements have not actually been taken. Synthetic seismic responses are computed through the integration of multiphase flow, a new thermodynamically consistent fluid substitution model, and a fast marching eikonal solver. We quantified uncertainty in first-arrival times to illustrate the potential utility of crosswell seismic surveys and their limitation. Consistent with these calculations, uncertainties in neutron capture cross-section logs are also computed and related to predicted [Formula: see text] migration. The predicted uncertainty range for neutron-capture measurements indicated significant sensitivity to the uncertainty of the reservoir properties (standard deviations [STDs] of up to 6 c.u. in the injector and up to 3.5 c.u. in the monitoring well). However, the STD of predicted time-lapse crosswell seismic responses for two different source locations did not exceed 0.75 ms during the life of the project, suggesting limited value of first-arrival measurements for reservoir-parameter inversion in this case. With the time-dependent uncertainty of the predicted measurements, calculated GSA indices provided a quantitative basis for the monitoring program design. Practical implications of GSA results for model reduction and subsequent inversion were also evaluated.
The upside of uncertainty: Identification of lithology contact zones from airborne geophysics and satellite data using random forests and support vector machines
Authors: Cracknell Matthew J. , Reading Anya M.
Published: May 2013

Inductive machine learning algorithms attempt to recognize patterns in, and generalize from empirical data. They provide a practical means of predicting lithology, or other spatially varying physical features, from multidimensional geophysical data sets. It is for this reason machine learning approaches are increasing in popularity for geophysical data inference. A key motivation for their use is the ease with which uncertainty measures can be estimated for nonprobabilistic algorithms. We have compared and evaluated the abilities of two nonprobabilistic machine learning algorithms, random forests (RF) and support vector machines (SVM), to recognize ambiguous supervised classification predictions using uncertainty calculated from estimates of class membership probabilities. We formulated a method to establish optimal uncertainty threshold values to identify and isolate the maximum number of incorrect predictions while preserving most of the correct classifications. This is illustrated using a case example of the supervised classification of surface lithologies in a folded, structurally complex, metamorphic terrain. We found that (1) the use of optimal uncertainty thresholds significantly improves overall classification accuracy of RF predictions, but not those of SVM, by eliminating the maximum number of incorrectly classified samples while preserving the maximum number of correctly classified samples; (2) RF, unlike SVM, was able to exploit dependencies and structures contained within spatially varying input data; and (3) high RF prediction uncertainty is spatially coincident with transitions in lithology and associated contact zones, and regions of intense deformation. Uncertainty has its upside in the identification of areas of key geologic interest and has wide application across the geosciences, where transition zones are important classes in their own right. The techniques used in this study are of practical value in prioritizing subsequent geologic field activities, which, with the aid of this analysis, may be focused on key lithology contacts and problematic localities.
Haunting the Queer Spaces of AIDS
Authors: Gill-Peterson Julian
Published: May 2013

This essay considers the mutation of the temporality of HIV/AIDS in the United States from epidemic time to endemic time — the biopolitical distribution of life and death capacities across populations — as a critical noncoincidence of the present with itself. That the present moment is “out of joint” for the two generations separated by the interval between epidemic and endemic time is the motivation for asking a series of ethical, historical, and political questions about HIV/AIDS and queer theory through the lens of Jacques Derrida's Specters of Marx and the New York City – based digital archive of the AIDS Coalition to Unleash Power (ACT UP) Oral History Project. Hauntology, a nonlinear process concomitant with archiving, is the ground from which, in the case of ACT UP/New York, the reactive endurance of life under neoliberalism in the archived memory of AIDS activism is made available for an active invention of a new ethico-political project across the generations otherwise divided by the aporia between epidemic and endemic.
Dynamic Trafficking of STAT5 Depends on an Unconventional Nuclear Localization Signal
Authors: Shin Ha Youn , Reich Nancy C.
Published: May 2013

Signal transducer and activator of transcription 5 (STAT5) is critical for physiological processes that include hematopoiesis, liver metabolism, and mammary gland development. However, aberrant continual activity of STAT5 has been causally linked to human leukemias and solid tumor formation. As a regulated transcription factor, precise cellular localization of STAT5 is essential. Conventional nuclear localization signals consist of short stretches of basic amino acids. In this study we provide evidence that STAT5 nuclear import is dependent on an unconventional nuclear localization signal that functions within the conformation of an extensive coiled-coil domain. Both in vitro binding and in vivo functional assays reveal that STAT5 nuclear import is mediated by the importin-α3/β1 system independent of STAT5 activation by tyrosine phosphorylation. The integrity of the coiled-coil domain is essential for STAT5 transcriptional induction of the β-casein gene following prolactin stimulation, as well as its ability to synergize with the glucocorticoid receptor. The glucocorticoid receptor accumulates in the nucleus in response to prolactin, and this nuclear import is dependent on STAT5 nuclear import. STAT5 continually shuttles in and out of the nucleus, and live cell imaging demonstrates STAT5 nuclear export is mediated by both Crm1-dependent and Crm1-independent pathways. A Crm1-dependent nuclear export signal was identified within the STAT5 amino terminus. These findings provide insight to fundamental mechanisms that regulate STAT5 nuclear trafficking and cooperation with the glucocorticoid receptor, and provide a basis for clinical intervention of STAT5 function in disease.
Flt3L is a novel regulator of skeletal myogenesis
Authors: Ge Yejing , Waldemer Rachel J. , Nalluri Ramakrishna , Nuzzi Paul D. , Chen Jie
Published: May 2013

Various cues initiate multiple signaling pathways to regulate the highly coordinated process of skeletal myogenesis. Myoblast differentiation comprises a series of ordered events starting with cell cycle withdrawal and ending with myocyte fusion, each step likely controlled by multiple extracellular signals and intracellular signaling pathways. Here we report the identification of Flt3L (Fms-like tyrokine kinase 3 ligand) signaling as a novel regulator of skeletal myogenesis. Flt3L is a multifunctional cytokine in immune cells, but its involvement in skeletal muscle formation has not been reported. We find that Flt3L is expressed in C2C12 myoblasts, with increasing levels during differentiation. Knockdown of Flt3L, or its receptor Flt3, suppresses myoblast differentiation, which is rescued by recombinant Flt3L or Flt3, respectively. Differentiation is not rescued, however, by recombinant ligand when the receptor is knocked down, or vice versa, suggesting that Flt3L and Flt3 function together. Flt3L knockdown also inhibits differentiation in mouse primary myoblasts. Both Flt3L and Flt3 are highly expressed in nascent myofibers during muscle regeneration in vivo, and Flt3L siRNA impairs muscle regeneration, validating the physiological significance of Flt3L function in myogenesis. Providing a cellular mechanism for the myogenic function of Flt3L, we show that Flt3L promotes cell cycle exit that is necessary for myogenic differentiation. Furthermore, we identify Erk as a relevant target of Flt3L signaling during myogenesis, and demonstrate that Flt3L suppresses Erk signaling through p120RasGAP. In summary, our work reveals an unexpected role for an immunoregulatory cytokine in skeletal myogenesis and a new myogenic pathway.
Wilms’ tumour -a case of disrupted development
Authors: Miyagawa Kiyoshi , Kent Jill , Schedl Andreas , Heyningen Veronica van , Hastie Nicholas D.
Published: May 2013

Wilms’ tumour is a paediatric kidney malignancy that arises through aberrant differentiation of nephric stem cells. We are studying the role of one Wilms’ tumour predisposition gene, WT1. This is a tumour suppressor gene whose function is required for normal development of the genitourinary system. WT1 encodes a putative transcriptional repressor of the zinc finger family. Here we discuss how one of the normal functions of WT1 may be to suppress myogenesis during kidney development. Furthermore, we describe how we are proposing to use YAC (yeast artificial chromosome) transgenesis to analyse WT1 regulation and function in mice. We also discuss the evolution of the WT1 gene amongst different vertebrate classes and how this may provide insights into genitourinary evolution.
The role of cdc25 in checkpoints and feedback controls in the eukaryotic cell cycle
Authors: Hoffmann Ingrid , Karsenti Eric
Published: May 2013

Major checkpoints that gate progression through the cell cycle function at the G1/S transition, entry into mitosis and exit from mitosis. Cells use feedback mechanisms to inhibit passage through these checkpoints in response to growth control signals, incomplete DNA replication or spindle assembly. In many organisms, transition points seem to involve regulation of the activity of cyclin-dependent kinases (cdks) not only through their interactions with various cyclins, but also by phosphorylation-dephosphorylation cycles acting on the kinase activity of the cdks. These phosphorylation cycles are modulated by the regulation of the opposing kinases and phosphatases that act on cdks and form feedback loops. In this article, we discuss the role of positive and negative feedback loops in cell cycle timing and checkpoints, focusing more specifically on the regulation of the dual specificity cdc25 phosphatase.
pRB, p107 and the regulation of the E2F transcription factor
Authors: Dyson Nicholas
Published: May 2013

Small DNA tumor viruses, such as adenovirus, encode proteins that deregulate the cell cycle. These proteins are potent transforming agents when tested in standard oncogenic assays. For adenovirus the best characterized viral oncoproteins are the early region IA (E1A) products. Mutational studies have shown that ElA’s oncogenic ability is determined primarily by its ability to bind to certain cellular proteins and interfere with their function. One of these cellular targets for E1A is the product of the retinoblastoma tumor suppressor gene, pRB. pRB is a negative regulator of cell proliferation, and its inactivation has been shown to be an important oncogenic step in the development of many human cancers. In adenovirus-mediated transformation, E1A binds to pRB and inacti-vates it, thus functionally mimicking the loss of pRB often seen in human tumors.

There is now compelling evidence to suggest that pRB regulates transcription at specific phases of the cell cycle by physically associating with key transcription factors. The best characterized target of pRB is the transcription factor E2F. The interaction of pRB and E2F leads to the inhibition of E2F-mediated transactivation. Most of the genes that are known to be controlled by E2F have key roles in the regulation of cell proliferation. During cell cycle pro-gression, phosphorylation of pRB appears to change its conformation and E2F is released. In pathogenic settings E2F transactivation is not regulated by pRB binding. In human tumors with mutations in the retinoblastoma gene, functional pRB is absent and hence can no longer inhibit E2F activity. During adenovirus transformation, E1A binds to pRB and displaces E2F. In both these cases, E2F is released from pRB-mediated regulation at inappropriate times. The activation of these E2F-responsive genes may lead to the stimulation of cell proliferation. While we do not know whether E2F is the only target for pRB action, this work has formed a general picture of how tumor suppres-sor gene products such as pRB can control specific tran-scriptional events and act as negative regulators of cell growth.

Recent experiments have shown that E2F represents the combined activity of an extensive series of protein complexes. There are at least five genes that encode E2F polypeptides, and probably several more have yet to be identified. The E2F transcription factor is a heterodimer composed of two related polypeptides, one encoded by a member of the E2F gene family and the other by a member of the DP family. Intriguingly DP and E2F genes are also found in Drosophila and these may provide alternative approaches to the investigation of E2F function. In mammalian cells E2F/DP heterodimers are regulated, at least in part, by the formation of many larger complexes. E2F is found in separate complexes with pRB, p107/cyclin A/cdk2 or p107/cyclin E/cdk2, and additional complexes exist that have yet to be fully characterized. These E2F complexes are detected at specific points of the cell cycle and appear to provide different elements of E2F regulation.
Focal adhesion kinase: Structure and signalling
Authors: Parsons J. Thomas , Schaller Michael D. , Hildebrand Jeffrey , Leu Tzeng-Horng , Richardson Alan , Otey Carol
Published: May 2013

Studies on the attachment and spreading of cells in culture have provided valuable insights into the mechanisms by which cells transmit information from the outside to the inside of the cell. This brief review considers recent information on the role of focal adhesion-associated protein tyrosine kinases in integrin-regulated cell signalling.
Regulation and function of the MAP kinase cascade in Xenopus oocytes
Authors: Kosako Hidetaka , Gotoh Yukiko , Nishida Eisuke
Published: May 2013

In Xenopus oocytes, activation of MAP kinase occurs during meiotic maturation through a protein kinase cascade (the MAP kinase cascade), which is utilized commonly in various intracellular signaling pathways in eukaryotes. Studies with a neutralizing antibody against Xenopus MAP kinase kinase (MAPKK), a direct upstream activator for MAP kinase, have shown that the MAP kinase cascade plays a crucial role in both initiating oocyte matu- ration and inducing metaphase arrest.
Specificity in recognition of phosphopeptides by src-homology 2 domains
Authors: Cantley Lewis C. , Songyang Zhou
Published: May 2013

SH2 domains and SH3 domains, found in a number of protein-tyrosine kinases and substrates of protein-tyrosine kinases, provide specificity in downstream signaling. Both of these domains bind to relatively short linear sequences of peptides to provide specific interactions between proteins. The SH2 domains directly bind to phosphotyro- sine residues of proteins in a specific sequence context. We have devised a phosphopeptide library technique that allows us to rapidly determine the sequence specificity of individual SH2 domains on the basis of amino acids selected at position +1, +2 and +3 C-terminal of the phos- photyrosine. The optimal motif for 22 distinct SH2 domains has been determined and used to predict likely sites of in vivo interaction. A second phosphopeptide library was devised in which the amino acids N-terminal of the phos- photyrosine were also varied. The residues N-terminal of phosphotyrosine had little influence on binding to the N- SH2 domain of the 85 kDa subunit of phosphoinositide 3- kinase. These results indicate that for this SH2 domain, specificity is determined by sequences carboxy-terminal of the phosphotyrosine moiety. Knowledge of the specificity of SH2 domains allows predictions about likely downstream targets on the basis of primary sequence of proteins. Some of these predictions will be discussed.