bluuebunny/crossref_metadata_2025 huggingface dataset:
Protective effect of quercetin on lipopolysaccharide-induced acute lung injury in mice by inhibiting inflammatory cell influx
Authors: Wang Lian , Chen Jinming , Wang Bo , Wu Dingqian , Li Hao , Lu Huchen , Wu Haiwei , Chai Ying
Published: June 2014

Sepsis may result in lung injury through a complex cascade of events including interstitium infiltration of inflammatory cells. Quercetin, the most abundant dietary flavonoid found in various plants and food products, possesses potent anti-inflammatory and antioxidative properties. The purpose of this study was to investigate whether preventive administration of quercetin could exert beneficial effects on experimental septic acute lung injury induced by lipopolysaccharide (LPS). C57/BL6 mice were challenged with LPS and survival time was monitored from 0–96 h after LPS treatment. Quercetin markedly rescued lethality, improved survival time, and inhibited serum necrosis factor α, interleukin 1β, and interleukin 6, and nitric oxide (NO), and increased IL-10 secretion. Moreover, quercetin decreased lung pathological changes, myeloperoxidase activity, and malondialdehyde levels. Quercetin also reduced the lung permeability changes and neutrophil and macrophage recruitment to the bronchoalveolar lavage fluid compared to the vehicle. Additionally, quercetin significantly reduced COX-2, HMGB1, iNOS expression, and NF-κB p65 phosphorylation. These results suggest that treatment with quercetin in septic mice improved survival time and lung injury. Quercetin may be a promising potential therapeutic reagent for LPS-induced acute lung injury.
Complex influence of dermatan sulphate on breast cancer cells
Authors: Koźma Ewa M. , Wisowski Grzegorz , Latocha Małgorzata , Kusz Damian , Olczyk Krystyna
Published: June 2014

Tumor transformation and progression both lead to extracellular matrix remodeling, which is also reflected in an alteration in the proportion of dermatan sulphate (DS) and chondroitin sulphate (CS) and an accumulation of the latter. In addition, a significant increase in the 6-O-sulphated disaccharide contribution to the structure of both glycosaminoglycans has been observed. It is commonly accepted that CS is more permissive for tumor growth than DS. However, the detailed role of DS in tumor progression is poorly known. We tested the effects of structurally different DSs on the behavior of cultured breast cancer cells. At a high dose (10 µg/mL), all of the DSs significantly reduced cancer cell growth, although some differences in the efficiency of action were apparent. In contrast, when used at a concentration of 1 µg/mL, the examined DSs evoked different responses ranging from the stimulation to the inhibition of cancer cell proliferation. The highest stimulatory activity was associated with fibrosis-affected fascia decorin DS, which is characterized by a particularly high content of 6-O-sulphated disaccharides. Further reduction in DS concentration to 0.5 µg/mL preserved majority of biological effects which were apparent at a dose of 1 µg/mL. The enzymatic fragmentation of the DSs, particularly by chondroitinase AC I, abolished the impact exerted by 1 µg/mL of the intact DS chains and sometimes resulted in the opposite effect. In contrast to DSs, highly sulphated C-6-S exhibited no effect on the cancer cells. Our data revealed the complexity of the effects of DSs on breast cancer cells, which include both co-receptor activity and the prevention of vascular endothelial growth factor action. In addition, the biological effect of DSs is strongly dependent not only on the glycosaminoglycan structure but also on its content in the cancer environment.
Occupational stress and adaptation of immigrant nurses from the Philippines
Authors: Connor Jorgia Briones , Miller Arlene Michaels
Published: June 2014

Immigrant nurses face multiple challenges that create vulnerability to stress. The purpose of this study was to explore the stresses and work experiences of Filipino immigrant nurses. Specific aims were to identify the perceived sources of work-related and non-work-related stress and describe the factors that influence stress. A cross-sectional qualitative research design was used to gain a holistic understanding of the participants’ experiences. Twenty women, 28–48 years old, working as registered nurses in the Chicago metropolitan area were interviewed. The findings showed that participants faced resettlement demands because of unexpected social and living environments. They also experienced communication problems, discrimination and alienation, which interacted with and intensified work-related stressors. In addition, challenges arose from encountering cultural differences. Overall, this study illustrated that stress is dynamic, multidimensional and highly influenced by culture. These findings increase awareness of the types of stressors encountered by immigrant health care providers and urge health care administrators to develop and implement programmes to improve their quality of life. Recommendations for future studies include focusing on the outcomes of cumulative stress among immigrant health care providers.
Accuracy of Point-of-Care Blood Glucose Measurements in Critically Ill Patients in Shock
Authors: Garingarao Carlo Jan Pati-an , Buenaluz-Sedurante Myrna , Jimeno Cecilia Alegado
Published: June 2014

Background:

A widely used method in monitoring glycemic status of ICU patients is point-of-care (POC) monitoring devices. A possible limitation to this method is altered peripheral blood flow in patients in shock, which may result in over/underestimations of their true glycemic status.

Methods:

This study aims to determine the accuracy of blood glucose measurements with a POC meter compared to laboratory methods in critically ill patients in shock. POC blood glucose was measured with a glucose-1-dehydrogenase-based reflectometric meter. The reference method was venous plasma glucose measured by a clinical chemistry analyzer (glucose oxidase-based). Outcomes assessed were concordance to ISO 15197:2003 minimum accuracy criteria for glucose meters, bias in glucose measurements obtained by the 2 methods using Bland–Altman analysis, and clinical accuracy through modified error grid analysis.

Results:

A total of 186 paired glucose measurements were obtained. ISO 2003 accuracy criteria were met in 95.7% and 79.8% of POC glucose values in the normotensive and hypotensive group, respectively. Mean bias for the normotensive group was –12.4 mg/dL, while mean bias in the hypotensive group was –34.9 mg/dL.

Conclusions:

POC glucose measurements within the target zone for clinical accuracy were 90.2% and 79.8% for the normotensive and hypotensive group, respectively. POC blood glucose measurements were significantly less accurate in the hypotensive subgroup of ICU patients compared to the normotensive group. We recommend a lower threshold in confirming POC blood glucose with a central laboratory method if clinically incompatible. In light of recently updated accuracy standards, we also recommend alternative methods of glucose monitoring for the ICU population as a whole regardless of blood pressure status.
Experiences of Racial Microaggression Among Migrant Nurses in the United Kingdom
Authors: Estacio Emee Vida , Saidy-Khan Sirandou
Published: June 2014

In this article, we explore the experiences of racial microaggression among migrant nurses in the United Kingdom. Eleven migrant nurses kept a reflective diary for 6 weeks to record and reflect on their experiences of living and working in the United Kingdom. The diary entries were then thematically analyzed. The results suggest that migrant nurses experienced racial microaggression from patients and colleagues through racial preferences and bullying. Institutional racism also hindered their opportunities for further training and promotion. As a result, some experienced feelings of anger, frustration, and even paranoia. Despite the negative consequences of racial microaggression on their emotional well-being, incidents were downplayed as trivial because of their vague and subtle nature. To encourage better multicultural interactions in the workplace, supportive organizational infrastructures need to be in place to enhance diversity awareness and to improve mechanisms for reporting and dealing with cases of racial microaggression.
Electrochemical behaviour in process of electrodeposition Ni–P alloy coating
Authors: Wang Y. , Kang M. , Jin S. W. , Fu X. Q. , Wang X. S.
Published: June 2014

An Ni–P alloy coating was obtained by electrodeposition on a 45 carbon steel substrate. The surface appearance of the coating was characterised by Hitachi S-4800 scanning electron microscope. The electrodeposition behaviour was investigated using electrochemical methods. The results showed that the Ni–P alloy coating was dense and smooth. The electrodeposition of the Ni–P alloy followed the mechanism of three-dimensional nucleation and subsequent grain growth. The main deposition process changed from heterogeneous nucleation/growth of Ni onto the 45 carbon steel substrate to heterogeneous nucleation/growth of Ni–P onto Ni film. There was low frequency scatter on electrochemical impedance spectroscopy plots, which can be attributed to the production of gas. With increasing negative bias voltage, the low frequency scatter became more obvious, and the charge transfer resistances Rct and Rp increased.
Microstructure and tribological properties of REs borided TC21 alloy
Authors: Zhu Y. S. , Lu W. Z. , Zuo D. W. , Feng W. , He Y. F.
Published: June 2014

The hard titanium boride layers are produced on titanium alloy TC21 using rare earth (RE) additions boriding technique. The microstructural evolution and phase transformations of the boride layers are examined using scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy and X-ray diffraction. Moreover, the friction and wear behaviour of boride layers under dry sliding conditions are evaluated using an HT-1000 friction and wear tester, and the microstructures of worn surfaces are also characterised by SEM. The results show that the boron concentrations in the surface layer during surface boriding have been improved with a small amount of RE additions, coupled with enhanced surface hardness and coating layer thickness. Moreover, all of the borided alloys appear to have better wear resistance and lower friction coefficient than as received alloy; furthermore, the RE borided samples show higher hardness and better wear resistance than conventional one, without RE additions.
Microstructural studies of e-beam evaporated alumina thin films
Authors: Reddy I. N. , Reddy V. R. , Dey A. , Sridhara N. , Basavaraja S. , Bera P. , Anandan C. , Sharma A. K.
Published: June 2014

Alumina thin films of different thicknesses, e.g. 90, 120 and 150 nm, were grown on SS304 thin foil by electron beam evaporation technique. The films were post-heat treated at 500, 700 and 800°C in air and subsequently characterised by X-ray diffraction, atomic force microscopy, field emission scanning electron microscopy and X-ray photoelectron spectroscopy. The effects of thicknesses and post-heat treatment on microstructure have been studied. The deposited alumina film was almost stoichiometric. The alumina film of the lowest thickness, i.e. 90 nm post-heat treated at 700°C, showed preferential growth of nanorods and irregular polygonal nanostructures with random orientation.
Effects of fibre length on characteristics of brush plating coating
Authors: Jin G. , Hou D. , Hu Z. , Li J. , Cui X. , Xu B.
Published: June 2014

This paper explores the possibility that flexible fibres of different lengths substitute for sheath to fulfil brush plating from the perspective of optimising solution carrier. SEM, EDS, XRD, TEM, microhardness tester are respectively adopted to study the effects of fibre length on coatings’ morphology, structure and hardness. The results indicate that compared with sheath brush plating, fibre length greatly influences morphology, grain size, hardness of coatings. The existence of a large number of grain boundaries and proper defect densities will prevent the dislocation moving, therefore, mechanical properties like hardness of coatings will be improved.
Hydroxyurea-inducible SAR1 gene acts through the Giα/JNK/Jun pathway to regulate γ-globin expression
Authors: Zhu Jianqiong , Chin Kyung , Aerbajinai Wulin , Kumkhaek Chutima , Li Hongzhen , Rodgers Griffin P.
Published: June 2014

Key Points

Hydroxyurea activates nuclear factor–κB to transcriptionally upregulate SAR1. SAR1, in turn, activates γ-globin expression through the Giα/JNK/Jun pathway.
Hematopoietic stem cell transplantation donor sources in the 21st century: choosing the ideal donor when a perfect match does not exist
Authors: Kekre Natasha , Antin Joseph H.
Published: June 2014

Most patients who require allogeneic stem cell transplantation do not have a matched sibling donor, and many patients do not have a matched unrelated donor. In an effort to increase the applicability of transplantation, alternative donors such as mismatched adult unrelated donors, haploidentical related donors, and umbilical cord blood stem cell products are frequently used when a well matched donor is unavailable. We do not yet have the benefit of randomized trials comparing alternative donor stem cell sources to inform the choice of donor; however, the existing data allow some inferences to be made on the basis of existing observational and phase 2 studies. All 3 alternative donor sources can provide effective lymphohematopoietic reconstitution, but time to engraftment, graft failure rate, graft-versus-host disease, transplant-related mortality, and relapse risk vary by donor source. These factors all contribute to survival outcomes and an understanding of them should help guide clinicians when choosing among alternative donor sources when a matched related or matched unrelated donor is not available.
Identification of cereblon-binding proteins and relationship with response and survival after IMiDs in multiple myeloma
Authors: Zhu Yuan Xiao , Braggio Esteban , Shi Chang-Xin , Kortuem K. Martin , Bruins Laura A. , Schmidt Jessica E. , Chang Xiu-Bao , Langlais Paul , Luo Moulun , Jedlowski Patrick , LaPlant Betsy , Laumann Kristina , Fonseca Rafael , Bergsagel P. Leif , Mikhael Joseph , Lacy Martha , Champion Mia D. , Stewart A. Keith
Published: June 2014

Key Points

We identified CRBN-binding proteins and confirmed recent work implicating the Ikaros transcription factors as important members. Low IZKF1 levels predict lack of IMiD responsiveness and shorter OS; IZKF1 expression is a potential predictive biomarker for clinic application.
Integrating the interactome and the transcriptome of Drosophila
Authors: Murali Thilakam , Pacifico Svetlana , Finley Russell L
Published: June 2014

Background

Networks of interacting genes and gene products mediate most cellular and developmental processes. High throughput screening methods combined with literature curation are identifying many of the protein-protein interactions (PPI) and protein-DNA interactions (PDI) that constitute these networks. Most of the detection methods, however, fail to identify thein vivospatial or temporal context of the interactions. Thus, the interaction data are a composite of the individual networks that may operate in specific tissues or developmental stages. Genome-wide expression data may be useful for filtering interaction data to identify the subnetworks that operate in specific spatial or temporal contexts. Here we take advantage of the extensive interaction and expression data available forDrosophilato analyze how interaction networks may be unique to specific tissues and developmental stages.

Results

We ranked genes on a scale from ubiquitously expressed to tissue or stage specific and examined their interaction patterns. Interestingly, ubiquitously expressed genes have many more interactions among themselves than do non-ubiquitously expressed genes both in PPI and PDI networks. While the PDI network is enriched for interactions between tissue-specific transcription factors and their tissue-specific targets, a preponderance of the PDI interactions are between ubiquitous and non-ubiquitously expressed genes and proteins. In contrast to PDI, PPI networks are depleted for interactions among tissue- or stage- specific proteins, which instead interact primarily with widely expressed proteins. In light of these findings, we present an approach to filter interaction data based on gene expression levels normalized across tissues or developmental stages. We show that this filter (the percent maximum or pmax filter) can be used to identify subnetworks that function within individual tissues or developmental stages.

Conclusions

These observations suggest that protein networks are frequently organized into hubs of widely expressed proteins to which are attached various tissue- or stage-specific proteins. This is consistent with earlier analyses of human PPI data and suggests a similar organization of interaction networks across species. This organization implies that tissue or stage specific networks can be best identified from interactome data by using filters designed to include both ubiquitously expressed and specifically expressed genes and proteins.
Design of a flexible component gathering algorithm for converting cell-based models to graph representations for use in evolutionary search
Authors: Budnikova Marianna , Habig Jeffrey W , Lobo Daniel , Cornia Nicolas , Levin Michael , Andersen Tim
Published: June 2014

Background

The ability of science to produce experimental data has outpaced the ability to effectively visualize and integrate the data into a conceptual framework that can further higher order understanding. Multidimensional and shape-based observational data of regenerative biology presents a particularly daunting challenge in this regard. Large amounts of data are available in regenerative biology, but little progress has been made in understanding how organisms such as planaria robustly achieve and maintain body form. An example of this kind of data can be found in a new repository (PlanformDB) that encodes descriptions of planaria experiments and morphological outcomes using a graph formalism.

Results

We are developing a model discovery framework that uses a cell-based modeling platform combined with evolutionary search to automatically search for and identify plausible mechanisms for the biological behavior described in PlanformDB. To automate the evolutionary search we developed a way to compare the output of the modeling platform to the morphological descriptions stored in PlanformDB. We used a flexible connected component algorithm to create a graph representation of the virtual worm from the robust, cell-based simulation data. These graphs can then be validated and compared with target data from PlanformDB using the well-known graph-edit distance calculation, which provides a quantitative metric of similarity between graphs. The graph edit distance calculation was integrated into a fitness function that was able to guide automated searches for unbiased models of planarian regeneration. We present a cell-based model of planarian that can regenerate anatomical regions following bisection of the organism, and show that the automated model discovery framework is capable of searching for and finding models of planarian regeneration that match experimental data stored in PlanformDB.

Conclusion

The work presented here, including our algorithm for converting cell-based models into graphs for comparison with data stored in an external data repository, has made feasible the automated development, training, and validation of computational models using morphology-based data. This work is part of an ongoing project to automate the search process, which will greatly expand our ability to identify, consider, and test biological mechanisms in the field of regenerative biology.
Practice of skin protection and skin care among German surgeons and influence on the efficacy of surgical hand disinfection and surgical glove perforation
Authors: Harnoss Julian C , Brune Laura , Ansorg Jörg , Heidecke Claus-Dieter , Assadian Ojan , Kramer Axel
Published: June 2014

Background

Surgical hand rub and healthy skin are basic requirements to prevent surgical site infections. Nevertheless, there is little knowledge about the current practice of skin protection and/or skin care products (SP/SC) using among surgeons as well as a lack of data pertaining to the influence of SP/SC on the antimicrobial efficacy of surgical hand rub.

Methods

A 10 weeks-survey among German surgeons as well as an experimental crossover study involving 26 participants were conducted. The immediate and sustainable efficacy (IE/SE) of surgical hand rub and participants’ hand moisture were measured after an 8-day usage of SP/SC, as well as the influence on micro-perforations on surgical gloves.

Results

The questionnaire was available to 16,000 German surgeons. Thereof, 1,771 surgeons accessed the questionnaire, representing a total participation rate of 11%. As 19% (n = 338) of questionnaires were incomplete, a total of 1,433 completed questionnaires were available for further analysis. More than 75% of the participants stated not to use any SP/SC, yet, almost 50% suffered from skin irritation or discomfort. Only 5% used SP/SC at the beginning of their shift. 10% refused to use SP/SC because of concerns that SP/SC may reduce the antimicrobial efficacy of surgical hand rub.

After usage of SP/SC over 8-days, skin moisture was significantly higher (P < 0.001), whereas no significant influence on the antimicrobial efficacy of surgical hand rub was observed (IE: P = 0.135; SP: P = 0.681). Micro-perforations were detected in 8/52 surgical gloves (15%), with no statistical significant difference between SP/SC users (n = 2/26; 8%) and non-users (n = 6/26; 23%; P = 0.249).

Conclusions

Following the results of this largest questionnaire base survey among German surgeons on skin care, there is a need to educate and inform surgeons on the correct application and the concept of SP/SC strategies. In the present study, the combination of selected SP/SC products and one alcohol-based hand rub formulation did not show a negative interaction with surgical hand rub or surgical glove perforation. However, it is advisable to ascertain the compatibility of SP/SC products with the used hand disinfectant prior to purchase.
Stochastic switching of TiO2-based memristive devices with identical initial memory states
Authors: Li Qingjiang , Khiat Ali , Salaoru Iulia , Xu Hui , Prodromakis Themistoklis
Published: June 2014

In this work, we show that identical TiO2-based memristive devices that possess the same initial resistive states are only phenomenologically similar as their internal structures may vary significantly, which could render quite dissimilar switching dynamics. We experimentally demonstrated that the resistive switching of practical devices with similar initial states could occur at different programming stimuli cycles. We argue that similar memory states can be transcribed via numerous distinct active core states through the dissimilar reduced TiO2-x
filamentary distributions. Our hypothesis was finally verified via simulated results of the memory state evolution, by taking into account dissimilar initial filamentary distribution.
No evidence for LGV transmission among heterosexuals in Amsterdam, the Netherlands
Authors: Heiligenberg Marlies , Verweij Stephan P , Speksnijder Arjen GCL , Morré Servaas A , de Vries Henry JC , Schim van der Loeff Maarten F
Published: June 2014

Background

In recent years a few cases of lymphogranuloma venereum (LGV) in heterosexuals in Europe have been reported. It is not known whether LGV transmission among heterosexuals occurs on a wider scale.

Methods

Heterosexual male and female STI clinic clients (n = 587) in Amsterdam, the Netherlands, with a positive nucleic acid amplification test (NAAT) result for Chlamydia trachomatis (CT) were screened for IgA anti-MOMP in serum. If the value was above the cut-off index (2.0) the patient’s CT positive urogenital, ocular or rectal sample(s) were selected and tested for LGV by an in-house LGV-specific NAAT.

Results

Sera of 126 patients were above 2.0 COI. Some patients had >1 CT positive sample. Samples could not be retrieved from 15 of the 126 persons, and 7 samples that were found positive for CT in the diagnostic amplification process could not be confirmed and hence not typed. We did not find a single case of LGV infection in 123 urogenital, ocular or rectal samples from 104 patients.

Conclusion

We found no indications for significant spread of LGV infection in heterosexuals in Amsterdam. Surveillance in females with cervical or anal CT infection is indicated to monitor LGV occurrence in heterosexuals.
Programmatic Variation in Home Hemodialysis in Canada: Results from a Nationwide Survey of Practice Patterns
Authors: Pauly Robert P , Komenda Paul , Chan Christopher T , Copland Michael , Gangji Azim , Hirsch David , Lindsay Robert , MacKinnon Martin , MacRae Jennifer M , McFarlane Philip , Nesrallah Gihad , Pierratos Andreas , Plaisance Martin , Reintjes Frances , Rioux Jean-Philippe , Shik John , Steele Andrew , Stryker Rod , Wu George , Zimmerman Deborah L
Published: June 2014

Background:

Over 40% of patients with end stage renal disease in the United States were treated with home hemodialysis (HHD) in the early 1970's. However, this number declined rapidly over the ensuing decades so that the overwhelming majority of patients were treated in-centre 3 times per week on a 3–4 hour schedule. Poor outcomes for patients treated in this fashion led to a renewed interest in home hemodialysis, with more intensive dialysis schedules including short daily (SDHD) and nocturnal (NHD). The relative infancy of these treatment schedules means that there is a paucity of data on ‘how to do it’.

Objective:

We undertook a systematic survey of home hemodialysis programs in Canada to describe current practice patterns.

Design:

Development and deployment of a qualitative survey instrument.

Setting:

Community and academic HHD programs in Canada.

Participants:

Physicians, nurses and technologists.

Measurements:

Programmatic approaches to patient selection, delivery of dialysis, human resources available, and follow up.

Methods:

We developed the survey instrument in three phases. A focus group of Canadian nephrologists with expertise in NHD or SDHD discussed the scope the study and wrote questions on 11 domains. Three nephrologists familiar with all aspects of HHD delivery reviewed this for content validity, followed by further feedback from the whole group. Multidisciplinary teams at three sites pretested the survey and further suggestions were incorporated. In July 2010 we distributed the survey electronically to all renal programs known to offer HHD according to the Canadian Organ Replacement Registry. We compiled the survey results using qualitative and quantitative methods, as appropriate.

Results:

Of the academic and community programs that were invited to participate, 80% and 63%, respectively, completed the survey. We observed wide variation in programmatic approaches to patient recruitment, human resources, equipment, water, vascular access, patient training, dialysis prescription, home requirements, patient follow up, medications, and the approach to non-adherent patients.

Limitations:

Cross-sectional survey, unable to link variation to outcomes. Competition for patients between HHD and home peritoneal dialysis means that case mix for HHD may also vary between centres.

Conclusions:

There is wide variation between programs in all domains of HHD delivery in Canada. We plan further study of the extent to which differences in approach are related to outcomes.
Mesenchymal precursor cells maintain the differentiation and proliferation potentials of breast epithelial cells
Authors: Duss Stephan , Brinkhaus Heike , Britschgi Adrian , Cabuy Erik , Frey Daniel M , Schaefer Dirk J , Bentires-Alj Mohamed
Published: June 2014

Introduction

Stromal-epithelial interactions play a fundamental role in tissue homeostasis, controlling cell proliferation and differentiation. Not surprisingly, aberrant stromal-epithelial interactions contribute to malignancies. Studies of the cellular and molecular mechanisms underlying these interactions require ex vivo experimental model systems that recapitulate the complexity of human tissue without compromising the differentiation and proliferation potentials of human primary cells.

Methods

We isolated and characterized human breast epithelial and mesenchymal precursors from reduction mammoplasty tissue and tagged them with lentiviral vectors. We assembled heterotypic co-cultures and compared mesenchymal and epithelial cells to cells in corresponding monocultures by analyzing growth, differentiation potentials, and gene expression profiles.

Results

We show that heterotypic culture of non-immortalized human primary breast epithelial and mesenchymal precursors maintains their proliferation and differentiation potentials and constrains their growth. We further describe the gene expression profiles of stromal and epithelial cells in co-cultures and monocultures and show increased expression of the tumor growth factor beta (TGFβ) family member inhibin beta A (INHBA) in mesenchymal cells grown as co-cultures compared with monocultures. Notably, overexpression of INHBA in mesenchymal cells increases colony formation potential of epithelial cells, suggesting that it contributes to the dynamic reciprocity between breast mesenchymal and epithelial cells.

Conclusions

The described heterotypic co-culture system will prove useful for further characterization of the molecular mechanisms mediating interactions between human normal or neoplastic breast epithelial cells and the stroma, and will provide a framework to test the relevance of the ever-increasing number of oncogenomic alterations identified in human breast cancer.
Mapping-by-sequencing accelerates forward genetics in barley
Authors: Mascher Martin , Jost Matthias , Kuon Joel-Elias , Himmelbach Axel , Aßfalg Axel , Beier Sebastian , Scholz Uwe , Graner Andreas , Stein Nils
Published: June 2014

Mapping-by-sequencing has emerged as a powerful technique for genetic mapping in several plant and animal species. As this resequencing-based method requires a reference genome, its application to complex plant genomes with incomplete and fragmented sequence resources remains challenging. We perform exome sequencing of phenotypic bulks of a mapping population of barley segregating for a mutant phenotype that increases the rate of leaf initiation. Read depth analysis identifies a candidate gene, which is confirmed by the analysis of independent mutant alleles. Our method illustrates how the genomic resources of barley together with exome resequencing can underpin mapping-by-sequencing.
Effect of Communication Skills Training Program for Oncologists Based on Patient Preferences for Communication When Receiving Bad News: A Randomized Controlled Trial
Authors: Fujimori Maiko , Shirai Yuki , Asai Mariko , Kubota Kaoru , Katsumata Noriyuki , Uchitomi Yosuke
Published: June 2014

Purpose

The aim of this study was to identify the effects of a communication skills training (CST) program for oncologists, developed based on patient preferences regarding oncologists' communication.

Participants and Methods

Thirty oncologists were randomly assigned to either an intervention group (IG; 2-day CST workshop) or control group (CG). Participants were assessed on their communication performance during simulated consultation and their confidence in communicating with patients at baseline and follow-up. A total of 1,192 patients (response rate, 84.6%) who had consultations with the participating oncologists at baseline and/or follow-up were assessed regarding their distress using the Hospital Anxiety and Depression Scale, satisfaction with the consultation, and trust in their oncologist after the consultation.

Results

At the follow-up survey, the performance scores of the IG had improved significantly, in terms of their emotional support (P = .011), setting up a supportive environment (P = .002), and ability to deliver information (P = .001), compared with those of the CG. Oncologists in the IG were rated higher at follow-up than those in the CG in terms of their confidence in themselves (P = .001). Patients who met with oncologists after they had undergone the CST were significantly less depressed than those who met with oncologists in the CG (P = .027). However, the CST program did not affect patient satisfaction with oncologists' style of communication.

Conclusion

A CST program based on patient preferences is effective for both oncologists and patients with cancer. Oncologists should consider CST as an approach to enhancing their communication skills.
Thyroid Hormone Receptor α Mutation Causes a Severe and Thyroxine-Resistant Skeletal Dysplasia in Female Mice
Authors: Bassett J. H. Duncan , Boyde Alan , Zikmund Tomas , Evans Holly , Croucher Peter I. , Zhu Xuguang , Park Jeong Won , Cheng Sheue-yann , Williams Graham R.
Published: June 2014

A new genetic disorder has been identified that results from mutation of THRA, encoding thyroid hormone receptor α1 (TRα1). Affected children have a high serum T3:T4 ratio and variable degrees of intellectual deficit and constipation but exhibit a consistently severe skeletal dysplasia. In an attempt to improve developmental delay and alleviate symptoms of hypothyroidism, patients are receiving varying doses and durations of T4 treatment, but responses have been inconsistent so far. Thra1PV/+ mice express a similar potent dominant-negative mutant TRα1 to affected individuals, and thus represent an excellent disease model. We hypothesized that Thra1PV/+ mice could be used to predict the skeletal outcome of human THRA mutations and determine whether prolonged treatment with a supraphysiological dose of T4 ameliorates the skeletal abnormalities. Adult female Thra1PV/+ mice had short stature, grossly abnormal bone morphology but normal bone strength despite high bone mass. Although T4 treatment suppressed TSH secretion, it had no effect on skeletal maturation, linear growth, or bone mineralization, thus demonstrating profound tissue resistance to thyroid hormone. Despite this, prolonged T4 treatment abnormally increased bone stiffness and strength, suggesting the potential for detrimental consequences in the long term. Our studies establish that TRα1 has an essential role in the developing and adult skeleton and predict that patients with different THRA mutations will display variable responses to T4 treatment, which depend on the severity of the causative mutation.
Macrophage Metalloelastase (MMP12) Regulates Adipose Tissue Expansion, Insulin Sensitivity, and Expression of Inducible Nitric Oxide Synthase
Authors: Lee Jung-Ting , Pamir Nathalie , Liu Ning-Chun , Kirk Elizabeth A. , Averill Michelle M. , Becker Lev , Larson Ilona , Hagman Derek K. , Foster-Schubert Karen E. , van Yserloo Brian , Bornfeldt Karin E. , LeBoeuf Renee C. , Kratz Mario , Heinecke Jay W.
Published: June 2014

Macrophage metalloelastase, a matrix metallopeptidase (MMP12) predominantly expressed by mature tissue macrophages, is implicated in pathological processes. However, physiological functions for MMP12 have not been described. Because mRNA levels for the enzyme increase markedly in adipose tissue of obese mice, we investigated the role of MMP12 in adipose tissue expansion and insulin resistance. In humans, MMP12 expression correlated positively and significantly with insulin resistance, TNF-α expression, and the number of CD14+CD206+ macrophages in adipose tissue. MMP12 was the most abundant matrix metallopeptidase detected by proteomic analysis of conditioned medium of M2 macrophages and dendritic cells. In contrast, it was detected only at low levels in bone marrow derived macrophages and M1 macrophages. When mice received a high-fat diet, adipose tissue mass increased and CD11b+F4/80+CD11c−macrophages accumulated to a greater extent in MMP12-deficient (Mmp12−/−) mice than in wild-type mice (Mmp12+/+). Despite being markedly more obese, fat-fed Mmp12−/− mice were more insulin sensitive than fat-fed Mmp12+/+ mice. Expression of inducible nitric oxide synthase (Nos2) by Mmp12−/− macrophages was significantly impaired both in vivo and in vitro, suggesting that MMP12 might mediate nitric oxide production during inflammation. We propose that MMP12 acts as a double-edged sword by promoting insulin resistance while combatting adipose tissue expansion.
Impact of Diet-Induced Obesity on Intestinal Stem Cells: Hyperproliferation but Impaired Intrinsic Function That Requires Insulin/IGF1
Authors: Mah Amanda T. , Van Landeghem Laurianne , Gavin Hannah E. , Magness Scott T. , Lund P. Kay
Published: June 2014

Nutrient intake regulates intestinal epithelial mass and crypt proliferation. Recent findings in model organisms and rodents indicate nutrient restriction impacts intestinal stem cells (ISC). Little is known about the impact of diet-induced obesity (DIO), a model of excess nutrient intake on ISC. We used a Sox9-EGFP reporter mouse to test the hypothesis that an adaptive response to DIO or associated hyperinsulinemia involves expansion and hyperproliferation of ISC. The Sox9-EGFP reporter mouse allows study and isolation of ISC, progenitors, and differentiated lineages based on different Sox9-EGFP expression levels. Sox9-EGFP mice were fed a high-fat diet for 20 weeks to induce DIO and compared with littermates fed low-fat rodent chow. Histology, fluorescence activated cell sorting, and mRNA analyses measured impact of DIO on jejunal crypt-villus morphometry, numbers, and proliferation of different Sox9-EGFP cell populations and gene expression. An in vitro culture assay directly assessed functional capacity of isolated ISC. DIO mice exhibited significant increases in body weight, plasma glucose, insulin, and insulin-like growth factor 1 (IGF1) levels and intestinal Igf1 mRNA. DIO mice had increased villus height and crypt density but decreased intestinal length and decreased numbers of Paneth and goblet cells. In vivo, DIO resulted in a selective expansion of Sox9-EGFPLow ISC and percentage of ISC in S-phase. ISC expansion significantly correlated with plasma insulin levels. In vitro, isolated ISC from DIO mice formed fewer enteroids in standard 3D Matrigel culture compared to controls, indicating impaired ISC function. This decreased enteroid formation in isolated ISC from DIO mice was rescued by exogenous insulin, IGF1, or both. We conclude that DIO induces specific increases in ISC and ISC hyperproliferation in vivo. However, isolated ISC from DIO mice have impaired intrinsic survival and growth in vitro that can be rescued by exogenous insulin or IGF1.
Thyroid Antibody Status, Subclinical Hypothyroidism, and the Risk of Coronary Heart Disease: An Individual Participant Data Analysis
Authors: Collet Tinh-Hai , Bauer Douglas C. , Cappola Anne R. , Åsvold Bjørn O. , Weiler Stefan , Vittinghoff Eric , Gussekloo Jacobijn , Bremner Alexandra , den Elzen Wendy P. J. , Maciel Rui M. B. , Vanderpump Mark P. J. , Cornuz Jacques , Dörr Marcus , Wallaschofski Henri , Newman Anne B. , Sgarbi José A. , Razvi Salman , Völzke Henry , Walsh John P. , Aujesky Drahomir , Rodondi Nicolas
Published: June 2014

Context:

Subclinical hypothyroidism has been associated with increased risk of coronary heart disease (CHD), particularly with thyrotropin levels of 10.0 mIU/L or greater. The measurement of thyroid antibodies helps predict the progression to overt hypothyroidism, but it is unclear whether thyroid autoimmunity independently affects CHD risk.

Objective:

The objective of the study was to compare the CHD risk of subclinical hypothyroidism with and without thyroid peroxidase antibodies (TPOAbs).

Data Sources and Study Selection:

A MEDLINE and EMBASE search from 1950 to 2011 was conducted for prospective cohorts, reporting baseline thyroid function, antibodies, and CHD outcomes.

Data Extraction:

Individual data of 38 274 participants from six cohorts for CHD mortality followed up for 460 333 person-years and 33 394 participants from four cohorts for CHD events.

Data Synthesis:

Among 38 274 adults (median age 55 y, 63% women), 1691 (4.4%) had subclinical hypothyroidism, of whom 775 (45.8%) had positive TPOAbs. During follow-up, 1436 participants died of CHD and 3285 had CHD events. Compared with euthyroid individuals, age- and gender-adjusted risks of CHD mortality in subclinical hypothyroidism were similar among individuals with and without TPOAbs [hazard ratio (HR) 1.15, 95% confidence interval (CI) 0.87–1.53 vs HR 1.26, CI 1.01–1.58, P for interaction = .62], as were risks of CHD events (HR 1.16, CI 0.87–1.56 vs HR 1.26, CI 1.02–1.56, P for interaction = .65). Risks of CHD mortality and events increased with higher thyrotropin, but within each stratum, risks did not differ by TPOAb status.

Conclusions:

CHD risk associated with subclinical hypothyroidism did not differ by TPOAb status, suggesting that biomarkers of thyroid autoimmunity do not add independent prognostic information for CHD outcomes.
Genetic Evaluation of Short Stature
Authors: Dauber Andrew , Rosenfeld Ron G. , Hirschhorn Joel N.
Published: June 2014

Context:

Genetics plays a major role in determining an individual's height. Although there are many monogenic disorders that lead to perturbations in growth and result in short stature, there is still no consensus as to the role that genetic diagnostics should play in the evaluation of a child with short stature.

Evidence Acquisition:

A search of PubMed was performed, focusing on the genetic diagnosis of short stature as well as on specific diagnostic subgroups included in this article. Consensus guidelines were reviewed.

Evidence Synthesis:

There are a multitude of rare genetic causes of severe short stature. There is no high-quality evidence to define the optimal approach to the genetic evaluation of short stature. We review genetic etiologies of a number of diagnostic subgroups and propose an algorithm for genetic testing based on these subgroups.

Conclusion:

Advances in genomic technologies are revolutionizing the diagnostic approach to short stature. Endocrinologists must become facile with the use of genetic testing in order to identify the various monogenic disorders that present with short stature.
Combinatorial actions of Tgfβ and Activin ligands promote oligodendrocyte development and CNS myelination
Authors: Dutta Dipankar J. , Zameer Andleeb , Mariani John N. , Zhang Jingya , Asp Linnea , Huynh Jimmy , Mahase Sean , Laitman Benjamin M. , Argaw Azeb Tadesse , Mitiku Nesanet , Urbanski Mateusz , Melendez-Vasquez Carmen V. , Casaccia Patrizia , Hayot Fernand , Bottinger Erwin P. , Brown Chester W. , John Gareth R.
Published: June 2014

In the embryonic CNS, development of myelin-forming oligodendrocytes is limited by bone morphogenetic proteins, which constitute one arm of the transforming growth factor-β (Tgfβ) family and signal canonically via Smads 1/5/8. Tgfβ ligands and Activins comprise the other arm and signal via Smads 2/3, but their roles in oligodendrocyte development are incompletely characterized. Here, we report that Tgfβ ligands and activin B (ActB) act in concert in the mammalian spinal cord to promote oligodendrocyte generation and myelination. In mouse neural tube, newly specified oligodendrocyte progenitors (OLPs) are first exposed to Tgfβ ligands in isolation, then later in combination with ActB during maturation. In primary OLP cultures, Tgfβ1 and ActB differentially activate canonical Smad3 and non-canonical MAP kinase signaling. Both ligands enhance viability, and Tgfβ1 promotes proliferation while ActB supports maturation. Importantly, co-treatment strongly activates both signaling pathways, producing an additive effect on viability and enhancing both proliferation and differentiation such that mature oligodendrocyte numbers are substantially increased. Co-treatment promotes myelination in OLP-neuron co-cultures, and maturing oligodendrocytes in spinal cord white matter display strong Smad3 and MAP kinase activation. In spinal cords of ActB-deficient Inhbb−/− embryos, apoptosis in the oligodendrocyte lineage is increased and OLP numbers transiently reduced, but numbers, maturation and myelination recover during the first postnatal week. Smad3−/− mice display a more severe phenotype, including diminished viability and proliferation, persistently reduced mature and immature cell numbers, and delayed myelination. Collectively, these findings suggest that, in mammalian spinal cord, Tgfβ ligands and ActB together support oligodendrocyte development and myelin formation.
Small RNA profiling and characterization of piRNA clusters in the adult testes of the common marmoset, a model primate
Authors: Hirano Takamasa , Iwasaki Yuka W. , Lin Zachary Yu-Ching , Imamura Masanori , Seki Naomi M. , Sasaki Erika , Saito Kuniaki , Okano Hideyuki , Siomi Mikiko C. , Siomi Haruhiko
Published: June 2014

Small RNAs mediate gene silencing by binding Argonaute/Piwi proteins to regulate target RNAs. Here, we describe small RNA profiling of the adult testes of Callithrix jacchus, the common marmoset. The most abundant class of small RNAs in the adult testis was piRNAs, although 353 novel miRNAs but few endo-siRNAs were also identified. MARWI, a marmoset homolog of mouse MIWI and a very abundant PIWI in adult testes, associates with piRNAs that show characteristics of mouse pachytene piRNAs. As in other mammals, most marmoset piRNAs are derived from conserved clustered regions in the genome, which are annotated as intergenic regions. However, unlike in mice, marmoset piRNA clusters are also found on the X chromosome, suggesting escape from meiotic sex chromosome inactivation by the X-linked clusters. Some of the piRNA clusters identified contain antisense-orientated pseudogenes, suggesting the possibility that pseudogene-derived piRNAs may regulate parental functional protein-coding genes. More piRNAs map to transposable element (TE) subfamilies when they have copies in piRNA clusters. In addition, the strand bias observed for piRNAs mapped to each TE subfamily correlates with the polarity of copies inserted in clusters. These findings suggest that pachytene piRNA clusters determine the abundance and strand-bias of TE-derived piRNAs, may regulate protein-coding genes via pseudogene-derived piRNAs, and may even play roles in meiosis in the adult marmoset testis.
An Investigation of the Average Bid Mechanism for Procurement Auctions
Authors: Chang Wei-Shiun , Chen Bo , Salmon Timothy C.
Published: June 2014

In a procurement context, it can be quite costly for a buyer when the winning seller underestimates the cost of a project and then defaults on the project midway through completion. The average bid auction is one mechanism intended to help address this problem. This format involves awarding the contract to the bidder who has bid closest to the average of the bids submitted. We compare the performance of this mechanism with the standard low price mechanism to determine how successful the average bid format is in preventing bidder losses as well as its impact on the price paid by the buyer. We find the average bid mechanism to be more successful than expected because, surprisingly, bidding behavior remains similar between the average bid and low price auctions. We provide an explanation for the bidding behavior in the average bid auction that is based on subjects having problems processing signals near the extremes of the distribution.

This paper was accepted by Teck-Hua Ho, behavioral economics.