bluuebunny/crossref_metadata_2025 huggingface dataset:
Digital collaboration inside and outside educational systems
Authors: Birkeland Nils Rune , Drange Eli-Marie Danbolt , Tønnessen Elise Seip
Published: April 2015

This article takes its outset in findings from an ongoing research project investigating the use of digital and multimodal resources in teacher education (TE) in Norway. The material studied is mandatory assignments in different courses in TE, asking how teacher students collaborate through digital media in their production of texts for learning, and how the design of these literacy practices can be influenced through the teachers’ design of the assignments.

In focus group interviews the researchers found that the students preferred organizing collaborative processes through Facebook groups rather than through the university’s learning management system. This created a space between formal and informal learning, often mediated by “power users” performing a curatorial function on behalf of the group. Furthermore, the quality of the processes seemed to depend on how the assignments were designed for different modes and for individual or group work. The tasks that inspired genuine collaborative learning were characterized by a certain complexity in terms of multimodality and technology, or professional knowledge combining academic and practical experience. In other cases tasks to be performed in groups were split between the students, and probably did not add the same value to individual learning. This is discussed as an encounter between the teachers’ design of the assignments and the students’ design of their learning processes. When teacher students tell us how they work with assignments, they at the same time explain how their knowledge is designed through social and textual practices. Reflections on these practices are relevant to developing their awareness of didactic design in their future profession as teachers.
Simultaneous combined balloon‐occluded retrograde transvenous obliteration and partial splenic embolization for gastric fundal varices
Authors: Waguri Nobuo , Osaki Akihiko , Ikarashi Shunzo , Ogawa Masahiro , Kuraoka Naosuke , Ogawa Kohei , Sato Munehiro , Aiba Tsuneo , Yoneyama Osamu , Furukawa Koichi , Sugimura Kazuhito , Igarashi Kentarou
Published: April 2015

Background

We previously reported the techniques and usefulness of simultaneous combined balloon‐occluded retrograde transvenous obliteration (B‐RTO) and partial splenic embolization (PSE), based on the hypothesis that concomitant PSE can diminish the increase in portal venous pressure after B‐RTO.

Objective

After experiencing more cases and performing longer‐term follow‐up, we re‐evaluated the efficacy of simultaneous combined B‐RTO and PSE for gastric fundal varices (GVs).

Methods

We performed B‐RTO in 36 consecutive patients treated for GVs from 2005 to 2013. Twenty‐three patients underwent simultaneous combined B‐RTO and PSE (Group 1) and 13 underwent B‐RTO monotherapy (Group 2). The outcomes were retrospectively evaluated.

Results

There were no significant differences in baseline characteristics between the two groups except that the splenic volumes were larger in Group 1 than 2. B‐RTO was technically successful in 21 of 23 patients (91.3%) in Group 1 and in 12 of 13 patients (92.3%) in Group 2. In all patients with ruptured GVs (six in Group 1 and five in Group 2), complete hemostasis was obtained by B‐RTO. Exacerbation of esophageal varices was significantly less frequent in Group 1 than 2 (p  = 0.0017).

Conclusion

Concomitant PSE with B‐RTO may contribute to prevention of the exacerbation of esophageal varices after B‐RTO.
A Cost-Effectiveness Analysis of Community Health Workers in Mozambique
Authors: Bowser Diana , Okunogbe Adeyemi , Oliveras Elizabeth , Subramanian Laura , Morrill Tyler
Published: April 2015

Introduction: Community health worker (CHW) programs are a key strategy for reducing mortality and morbidity. Despite this, there is a gap in the literature on the cost and cost-effectiveness of CHW programs, especially in developing countries. Methods: This study assessed the costs of a CHW program in Mozambique over the period 2010-2012. Incremental cost-effectiveness ratios, comparing the change in costs to the change in 3 output measures, as well as gains in efficiency were calculated over the periods 2010-2011 and 2010-2012. The results were reported both excluding and including salaries for CHWs. Results: The results of the study showed total costs of the CHW program increased from US$1.34 million in 2010 to US$1.67 million in 2012. The highest incremental cost-effectiveness ratio was for the cost per beneficiary covered including CHW salaries, estimated at US$47.12 for 2010-2011. The smallest incremental cost-effectiveness ratio was for the cost per household visit not including CHW salaries, estimated at US$0.09 for 2010-2012. Adding CHW salaries would not only have increased total program costs by 362% in 2012 but also led to the largest efficiency gains in program implementation; a 56% gain in cost per output in the long run as compared with the short run after including CHW salaries. Conclusions: Our findings can be used to inform future CHW program policy both in Mozambique and in other countries, as well as provide a set of incremental cost per output measures to be used in benchmarking to other CHW costing analyses.
Tensions in the Press Box
Authors: Suggs David Welch
Published: April 2015

Sports journalists have long enjoyed close—many would say too close—relationships with their sources. As suggested by a neoinstitutionalist, understanding of organizational relationships, routines, and professional expectations become accepted over time by journalists and sports organizations alike. However, new competition from online media, as well as new opportunities for teams to bypass the media, have threatened the legitimacy of journalists and their work practices. A survey of 437 reporters and communications personnel found key differences in the ways those in the professions perceived access, suggesting that traditional work patterns are evolving in ways that could delegitimate journalists inside and outside sports.
Exploring Family-Oriented Markers of Adulthood
Authors: Hall Scott S. , Walls Jill K.
Published: April 2015

Previous studies have demonstrated a propensity for many emerging adults to minimize traditional indicators of adulthood, such as marriage and parenting. Beliefs about marriage and family are often ideological, especially within a contemporary, pluralistic society in which marriage and family have undergone significant transformations. The purpose of the current study was to investigate variation in how family-oriented roles and abilities were perceived as criteria for adulthood in a sample of emerging adult college students from several college campuses ( N = 651). An emphasis of the investigation was on possible associations with political ideology and factors related to identity and day-to-day intentions. A cluster analysis approach was used to identify four groups of individuals based on the importance they assigned to the markers. Multivariate analysis of covariance results revealed multiple differences among the cluster groups as they related to other markers of adulthood, political tendencies, and variables related to day-to-day intentions and well-being.
The Other Sex Work
Authors: Irvine Janice M.
Published: April 2015

This article examines subjective experiences of stigma by contemporary sociologists in the field of sexuality studies. Many sexuality scholars reported experiences of stigma and marginalization in academic departments, such as disparaging jokes and assumptions about the researcher’s personal sexual identity or behavior. Women were more likely than men to report these types of subjective experiences. Although preliminary, these findings suggest the possibility of stigma in the academic workplace based on the area of research.
Long non-coding RNA expression profiles predict metastasis in lymph node-negative breast cancer independently of traditional prognostic markers
Authors: Sørensen Kristina P , Thomassen Mads , Tan Qihua , Bak Martin , Cold Søren , Burton Mark , Larsen Martin J , Kruse Torben A
Published: April 2015

Introduction

Patients with clinically and pathologically similar breast tumors often have very different outcomes and treatment responses. Current prognostic markers allocate the majority of breast cancer patients to the high-risk group, yielding high sensitivities in expense of specificities below 20%, leading to considerable overtreatment, especially in lymph node-negative patients. Seventy percent would be cured by surgery and radiotherapy alone in this group. Thus, precise and early indicators of metastasis are highly desirable to reduce overtreatment. Previous prognostic RNA-profiling studies have only focused on the protein-coding part of the genome, however the human genome contains thousands of long non-coding RNAs (lncRNAs) and this unexplored field possesses large potential for identification of novel prognostic markers.

Methods

We evaluated lncRNA microarray data from 164 primary breast tumors from adjuvant naïve patients with a mean follow-up of 18 years. Eighty two patients who developed detectable distant metastasis were compared to 82 patients where no metastases were diagnosed. For validation, we determined the prognostic value of the lncRNA profiles by comparing the ability of the profiles to predict metastasis in two additional, previously-published, cohorts.

Results

We showed that lncRNA profiles could distinguish metastatic patients from non-metastatic patients with sensitivities above 90% and specificities of 64-65%. Furthermore; classifications were independent of traditional prognostic markers and time to metastasis.

Conclusions

To our knowledge, this is the first study investigating the prognostic potential of lncRNA profiles. Our study suggest that lncRNA profiles provide additional prognostic information and may contribute to the identification of early breast cancer patients eligible for adjuvant therapy, as well as early breast cancer patients that could avoid unnecessary systemic adjuvant therapy. This study emphasizes the potential role of lncRNAs in breast cancer prognosis.
Stromal-vascular fraction content and adipose stem cell behavior are altered in morbid obese and post bariatric surgery ex-obese women
Authors: Silva Karina R , Liechocki Sally , Carneiro João R , Claudio-da-Silva Cesar , Maya-Monteiro Clarissa M , Borojevic Radovan , Baptista Leandra S
Published: April 2015

Introduction

Subcutaneous adipose tissue is an interesting source of autologous stem cells with a fundamental role in the pathophysiology of obesity, metabolic syndromes and insulin resistance. We hypothesize that obesity could alter the stromal-vascular fraction (SVF) and adipose stem cell (ASCs) functions, which could compromise its regenerative behavior. Furthermore, we aimed to evaluate whether ASCs derived from post bariatric surgery ex-obese women maintain their functions in a similar fashion as do those from individuals who have never been obese.

Methods

The SVF of subcutaneous adipose tissue from control (n = 6, body mass index – BMI - 27.5 ± 0.5 kg/m2), obese (n = 12, BMI 46.2 ± 5.1 kg/m2) and post bariatric surgery ex-obese (n = 7, initial BMI 47.8 ± 1.3 kg/m2; final BMI 28.1 ± 1.1 kg/m2) women were isolated and evaluated by flow cytometry. ASCs were tested for lipid accumulation by perilipin, adipose differentiation-related protein (ADRP) and Oil Red O staining after adipogenic stimulus. The cytokines secreted by the ASCs and after lipid accumulation induction were also evaluated.

Results

The subcutaneous adipose tissue of obese and post bariatric surgery ex-obese women was enriched in pericytes (p = 0.0345). The number of supra-adventitial cells was not altered in the obese patients, but it was highly enriched in the post bariatric surgery ex-obese women (p = 0.0099). The ASCs of the post bariatric surgery ex-obese patients secreted more MCP-1 (monocyte chemoattractant protein-1; p = 0.0078). After lipid accumulation induction, the ASCs of the patients in all groups secreted less IL-6 than the ASCs with no adipogenic stimulus (p < 0.0001). Obese ASCs with lipid accumulation secreted the highest amount of IL-6 (p < 0.001) whereas the ASCs from the controls secreted the highest amount of adiponectin (p < 0.0001). The ASCs from the post bariatric surgery ex-obese patients showed the highest levels of lipid accumulation whereas those from the obese women had the lowest levels (p < 0.0001).

Conclusions

SVF content and ASC behavior are altered in the subcutaneous adipose tissue of morbid obese women; these changes are not completely restored after bariatric surgery-induced weight loss. The cellular alterations described in this study could affect the regenerative effects of adipose stem cells. Further investigations are required to avoid jeopardizing the development of autologous stem cell-based therapies.
Predicting poor peripheral blood stem cell collection in patients with multiple myeloma receiving pre-transplant induction therapy with novel agents and mobilized with cyclophosphamide plus granulocyte-colony stimulating factor: results from a Gruppo Italiano Malattie EMatologiche dell’Adulto Multiple Myeloma Working Party study
Authors: Musto Pellegrino , Simeon Vittorio , Grossi Alberto , Gay Francesca , Bringhen Sara , Larocca Alessandra , Guariglia Roberto , Pietrantuono Giuseppe , Villani Oreste , D’Arena Giovanni , Cuomo Carmela , Musto Clelia , Morabito Fortunato , Petrucci Maria Teresa , Offidani Massimo , Zamagni Elena , Tacchetti Paola , Conticello Concetta , Milone Giuseppe , Palumbo Antonio , Cavo Michele , Boccadoro Mario
Published: April 2015

Introduction

A still not well defined proportion of patients with multiple myeloma (MM) and eligible for autologous stem cell transplantation (AuSCT) fails to mobilize CD34+ peripheral blood stem cells (PBSC) at all or to collect an adequate number for a safe procedure or sufficient for multiple transplants. These so-called “poor-mobilizers” are difficult to be predicted, due to marked difference across previous heterogeneous studies.

Methods

We aimed to develop a method based on simple clinical parameters for predicting unsuccessful (<2 × 106/kg) or sub-optimal (<5 × 106/kg) collections of CD34+ PBSC in newly diagnosed MM patients eligible for AuSCT, treated with novel agents and receiving an homogeneous mobilizing therapy with cyclophosphamide and granulocyte-colony stimulating factor (G-CSF). To this purpose, 1,348 patients enrolled in five consecutive Italian clinical trials were retrospectively analysed. Age, baseline low peripheral blood cell counts, use of lenalidomide, and haematological toxicity developed during induction were taken into account as possible factors associated with poor mobilization.

Results

Overall, 280 patients (20.8%) showed either sub-optimal (167 patients, 12.4%) or unsuccessful (113 patients, 8.4%) collections. All analysed parameters negatively influenced the procedure, but only age and haematological toxicity during induction maintained their significance at multivariate analysis. Based on ordinal logistic regression model, we constructed a risk heat-map where the four parameters were pooled and weighted according to their relevance as single or combined variables. This model was predictive for different probabilities of failure, suboptimal or optimal outcomes.

Conclusions

We found that about one fifth of newly diagnosed MM fails to collect an adequate number of PBSC. Our model, based on a large group of patients treated frontline with novel agents and receiving the most popular mobilizing approach currently employed in Europe, is applicable in individual subjects and may contribute to the early identification of “poor mobilizer” phenotypes.
Biphasic monopolar electrical stimulation induces rapid and directed galvanotaxis in adult subependymal neural precursors
Authors: Babona-Pilipos Robart , Pritchard-Oh Alex , Popovic Milos R , Morshead Cindi M
Published: April 2015

Introduction

Following injury such as stroke, adult mammalian subependymal neural precursor cells (NPCs) are induced to proliferate and migrate toward the lesion site where they differentiate into neural cells, albeit with limited efficacy. We are interested in enhancing this migratory ability of NPCs with the long-term goal of promoting neural repair. Herein we build on our previous studies demonstrating that direct current electric fields (DCEFs) promote rapid and cathode-directed migration of undifferentiated adult NPCs (but not differentiated phenotypes) - a phenomenon known as galvanotaxis. While galvanotaxis represents a promising strategy to promote NPC recruitment to lesion sites, stimulation of neural tissue with DCEFs is not a clinically-viable strategy due to the associated accumulation of charge and toxic byproducts. Balanced biphasic waveforms prevent the accumulation of charge and thus are outside of the limitations of DCEFs. In this study, we investigated the effects of balanced biphasic electrical stimulation on the migratory behaviour of undifferentiated subependymal NPCs and their differentiated progeny.

Methods

NPCs were isolated from the subependymal zone of adult mouse brains and cultured in a NPC colony-forming assay to form neurospheres. Neurospheres were plated onto galvanotaxis chambers in conditions that either promoted maintenance in an undifferentiated state or promoted differentiation into mature phenotypes. Chambers containing cells were then time-lapse imaged in the presence of either biphasic monopolar, or biphasic bipolar electrical stimulation, or in the complete absence of electrical stimulation. Single cell migration was subsequently tracked and the cells’ magnitude of velocity, directedness and tortuosity were quantified.

Results

We demonstrate, for the first time, the use of balanced biphasic electric fields to induce galvanotaxis of NPCs. Undifferentiated adult mouse subependymal NPCs exposed to biphasic monopolar stimulation undergo rapid and directed migration toward the cathode. In contrast, both biphasic bipolar stimulation and the lack of electrical stimulation produced non-directed migration of NPCs. Notably, NPCs induced to differentiate into mature phenotypes prior to exposure to electrical stimulation do not migrate in the presence or absence of biphasic stimulation.

Conclusion

We purport that balanced biphasic stimulation represents a clinically-viable technique for mobilizing NPCs that may be integrated into strategies for promoting endogenous neurorepair.
Multiple intravenous injections of allogeneic equine mesenchymal stem cells do not induce a systemic inflammatory response but do alter lymphocyte subsets in healthy horses
Authors: Kol Amir , Wood Joshua A , Carrade Holt Danielle D , Gillette Jessica A , Bohannon-Worsley Laurie K , Puchalski Sarah M , Walker Naomi J , Clark Kaitlin C , Watson Johanna L , Borjesson Dori L
Published: April 2015

Introduction

Intravenous (IV) injection of mesenchymal stem cells (MSCs) is used to treat systemic human diseases and disorders but is not routinely used in equine therapy. In horses, MSCs are isolated primarily from adipose tissue (AT) or bone marrow (BM) and used for treatment of orthopedic injuries through one or more local injections. The objective of this study was to determine the safety and lymphocyte response to multiple allogeneic IV injections of either AT-derived MSCs (AT-MSCs) or BM-derived MSCs (BM-MSCs) to healthy horses.

Methods

We injected three doses of 25 × 106 allogeneic MSCs from either AT or BM (a total of 75 × 106 MSCs per horse) into five and five, respectively, healthy horses. Horses were followed up for 35 days after the first MSC infusion. We evaluated host inflammatory and immune response, including total leukocyte numbers, serum cytokine concentration, and splenic lymphocyte subsets.

Results

Repeated injection of allogeneic AT-MSCs or BM-MSCs did not elicit any clinical adverse effects. Repeated BM-MSC injection resulted in increased blood CD8+ T-cell numbers. Multiple BM-MSC injections also increased splenic regulatory T cell numbers compared with AT-MSC-injected horses but not controls.

Conclusions

These data demonstrate that multiple IV injections of allogeneic MSCs are well tolerated by healthy horses. No clinical signs or clinico-pathologic measurements of organ toxicity or systemic inflammatory response were recorded. Increased numbers of circulating CD8+ T cells after multiple IV injections of allogeneic BM-MSCs may indicate a mild allo-antigen-directed cytotoxic response. Safety and efficacy of allogeneic MSC IV infusions in sick horses remain to be determined.
Hematopoiesis: from start to immune reconstitution potential
Authors: Liang Haydn C-Y , Zúñiga-Pflücker Juan Carlos
Published: April 2015

The study of hematopoiesis has been a focus for developmental biologists for over 100 years. What started as a series of microscopic observations in different animal model systems has since evolved into studies of gene expression and regulation, and subsequent protein–protein interactions, cell surface protein expression profiling, and functional mapping of cell fates. In this review, we will discuss the milestone discoveries that have been achieved in the field of hematopoietic development, as well as the techniques that have been employed. Finally, we look toward the future and consider unresolved questions. We also reflect on one of the earliest realizations made in this area of study: that hematopoiesis is evolutionarily conserved, and as a consequence we reflect on the impacts of early and current discoveries and their clinical implications. The future direction of the study of hematopoietic stem cells will probably make use of pluripotent stem cells to yield specific immune cell lineages and eventual clinical applications.
Mesenchymal stem cells-regulated Treg cells suppress colitis-associated colorectal cancer
Authors: Tang Rui-jing , Shen Su-nan , Zhao Xiao-yin , Nie Yun-zhong , Xu Yu-jun , Ren Jing , Lv Ming-ming , Hou Ya-yi , Wang Ting-ting
Published: April 2015

Introduction

Previous studies have produced controversial results regarding whether mesenchymal stem cells (MSCs) promote or inhibit tumor development. Given the dual role of MSCs in inflammation and cancer, in this study the colitis-associated colorectal cancer (CAC) model was used to examine whether umbilical cord tissue-derived MSCs could prevent neoplasm by inhibiting chronic inflammation.

Methods

MSCs were obtained and identified using flow cytometry. Colitis-associated colorectal cancer model was induced using azoxymethane (AOM) and dextran sulfate sodium (DSS) and MSCs were injected intravenously twice. Levels of immune cells in mesenteric lymph node including regulatory T (Treg) cells were detected using flow cytometry. Naïve T cells and Jurkat cells were co-cultured with MSCs and the effect of MSCs on Treg cells differentiation was evaluated.

Results

After injection through tail vein, MSCs could migrate to colon and suppress colitis-related neoplasm. This tumor suppressive effect was characterized by longer colon length, decreased tumor numbers and decreased expression of Ki-67. Moreover, MSCs alleviated the pathology of inflammation in the colitis stage of CAC model and inhibited inflammation cytokines both in colon and serum. Furthermore, Treg cells were accumulated in mesenteric lymph node of MSCs-treated mice while the percentage of T helper cells 2 (Th2) and Th17 were not changed. Of note, MSCs secreted transforming growth factor-β (TGF-β) enhanced the induction of Treg cells from naïve T cells. The conditioned medium of MSCs also activated Smad2 signaling, which has been reported to regulate Treg cells.

Conclusions

These results proved that MSCs could migrate to colon tissues and induce the differentiation of Treg cells via Smad2 as so to inhibit the colitis and suppress the development of CAC.
Molecular differences between stromal cell populations from deciduous and permanent human teeth
Authors: Kaukua Nina , Chen Mo , Guarnieri Paolo , Dahl Markus , Lim Mei Ling , Yucel-Lindberg Tülay , Sundström Erik , Adameyko Igor , Mao Jeremy J , Fried Kaj
Published: April 2015

Introduction

Deciduous and permanent human teeth represent an excellent model system to study aging of stromal populations. Aging is tightly connected to self-renewal and proliferation and thus, mapping potential molecular differences in these characteristics between populations constitutes an important task.

Methods

Using specifically designed microarray panels, Real-Time Quantitative Polymerase Chain Reaction (RT q-PCR), Western blot, immunohistochemistry and siRNA-mediated knock down experiments, we have detected a number of molecules that were differentially expressed in dental pulp from deciduous and permanent teeth extracted from young children and adults, respectively.

Results

Among the differentially regulated genes, high-mobility group AT-hook 2 (HMGA2), a stem cell-associated marker, stood out as a remarkable example with a robust expression in deciduous pulp cells. siRNA-mediated knock down of HMGA2 expression in cultured deciduous pulp cells caused a down-regulated expression of the pluripotency marker NANOG. This finding indicates that HMGA2 is a pulpal stem cell regulatory factor. In addition to this, we discovered that several proliferation-related genes, including CDC2A and CDK4, were up-regulated in deciduous pulp cells, while matrix genes COL1A1, fibronectin and several signaling molecules, such as VEGF, FGFr-1 and IGFr-1 were up-regulated in the pulp cells from permanent teeth.

Conclusions

Taken together, our data suggest that deciduous pulp cells are more robust in self- renewal and proliferation, whereas adult dental pulp cells are more capable of signaling and matrix synthesis.
Adipose-derived mesenchymal stromal cells modulate tendon fibroblast responses to macrophage-induced inflammation in vitro
Authors: Manning Cionne N , Martel Catherine , Sakiyama-Elbert Shelly E , Silva Matthew J , Shah Shivam , Gelberman Richard H , Thomopoulos Stavros
Published: April 2015

Introduction

Macrophage-driven inflammation is a key feature of the early period following tendon repair, but excessive inflammation has been associated with poor clinical outcomes. Modulation of the inflammatory environment using molecular or cellular treatments may provide a means to enhance tendon healing.

Methods

To examine the effect of pro-inflammatory cytokines secreted by macrophages on tendon fibroblasts (TF), we established in vitro models of cytokine and macrophage-induced inflammation. Gene expression, protein expression, and cell viability assays were used to examine TF responses. In an effort to reduce the negative effects of inflammatory cytokines on TFs, adipose-derived mesenchymal stromal cells (ASCs) were incorporated into the model and their ability to modulate inflammation was investigated.

Results

The inflammatory cytokine interleukin 1 beta (IL-1β) and macrophages of varying phenotypes induced up-regulation of pro-inflammatory factors and matrix degradation factors and down-regulation of factors related to extracellular matrix formation by TFs in culture. ASCs did not suppress these presumably negative effects induced by IL-1β. However, ASC co-culture with M1 (pro-inflammatory) macrophages successfully suppressed the effects of M1 macrophages on TFs by inducing a phenotypic switch from a pro-inflammatory macrophage phenotype to an anti-inflammatory macrophage phenotype, thus resulting in exposure of TFs to lower levels of pro-inflammatory cytokines (e.g., IL-1β, tumor necrosis factor alpha (TNFα)).

Conclusions

These findings suggest that IL-1β and M1 macrophages are detrimental to tendon healing and that ASC-mediated modulation of the post-operative inflammatory response may be beneficial for tendon healing.
RETRACTED ARTICLE: Activation of Wnt/β-catenin signalling promotes mesenchymal stem cells to repair injured alveolar epithelium induced by lipopolysaccharide in mice
Authors: Cai Shi-xia , Liu Ai-ran , Chen Song , He Hong-li , Chen Qi-hong , Xu Jing-yuan , Pan Chun , Yang Yi , Guo Feng-mei , Huang Ying-zi , Liu Ling , Qiu Hai-bo
Published: April 2015

Introduction

Mesenchymal stem cells (MSCs) have potential for re-epithelization and recovery in acute respiratory distress syndrome (ARDS). In a previous in vitro study, the results showed that the canonical Wnt/β-catenin pathway promoted the differentiation of MSCs into type II alveolar epithelial cells, conferred resistance to oxidative stress, and promoted their migration, suggesting that the Wnt/β-catenin pathway might be one of the key mechanisms underling the therapeutic effect of mouse MSCs in ARDS.

Methods

Mouse MSCs stable transfected with β-catenin or green fluorescent protein control were transplanted intratracheally into the ARDS mice induced by lipopolysaccharide. Lung tissue injury and repair assessment were examined using haematoxylin and eosin staining, lung injury scoring, Masson’s trichrome staining and fibrosis scoring. Homing and differentiation of mouse MSCs were assayed by labelling and tracing MSCs using NIR815 dye, immunofluorescent staining, and Western immunoblot analysis. The inflammation and permeability were evaluated by detecting the cytokine and protein measurements in bronchoalveolar lavage fluid using enzyme-linked immunosorbent assay.

Results

In this study, β-catenin-overexpressing MSC engraftment led to more significant effects than the GFP controls, including the retention of the MSCs in the lung, differentiation into type II alveolar epithelial cells, improvement in alveolar epithelial permeability, and the pathologic impairment of the lung tissue.

Conclusion

These results suggest that the activation of canonical Wnt/β-catenin pathway by mouse MSCs by overexpressing β-catenin could further improve the protection of mouse MSCs against epithelial impair and the therapeutic effects of mouse MSCs in ARDS mice.
Influence of vascular endothelial growth factor stimulation and serum deprivation on gene activation patterns of human adipose tissue-derived stromal cells
Authors: Tratwal Josefine , Mathiasen Anders Bruun , Juhl Morten , Brorsen Sonja Kim , Kastrup Jens , Ekblond Annette
Published: April 2015

Introduction

Stimulation of mesenchymal stromal cells and adipose tissue-derived stromal cells (ASCs) with vascular endothelial growth factor (VEGF) has been used in multiple animal studies and clinical trials for regenerative purposes. VEGF stimulation is believed to promote angiogenesis and VEGF stimulation is usually performed under serum deprivation. Potential regenerative molecular mechanisms are numerous and the role of contributing factors is uncertain. The aim of the current study was to investigate the effect of in vitro serum deprivation and VEGF stimulation on gene expression patterns of ASCs.

Methods

Gene expressions of ASCs cultured in complete medium, ASCs cultured in serum-deprived medium and ASCs stimulated with VEGF in serum-deprived medium were compared. ASC characteristics according to criteria set by the International Society of Cellular Therapy were confirmed by flow cytometry. Microarray gene expressions were obtained using the Affymetrix HT HG-U133+ GeneChip®. Gene set enrichment analysis was performed using the Kyoto Encyclopedia of Genes and Genomes and gene ontology terms. Transcription of selected genes of interest was confirmed by quantitative PCR.

Results

Compared to ASCs in complete medium, 190 and 108 genes were significantly altered by serum deprivation and serum deprivation combined with VEGF, respectively. No significant differences in gene expression patterns between serum-deprived ASCs and serum-deprived ASCs combined with VEGF stimulation were found. Genes most prominently and significantly upregulated by both conditions were growth factors (IGF1, BMP6, PDGFD, FGF9), adhesion molecule CLSTN2, extracellular matrix-related proteins such as matricellular proteins SMOC2, SPON1 and ADAMTS12, and inhibitors of proliferation (JAG1). The most significantly downregulated genes included matrix metalloproteinases (MMP3, MMP1), and proliferation markers (CDKN3) and GREM2 (a BMP6 antagonist).

Conclusion

The decisive factor for the observed change in ASC gene expression proves to be serum starvation rather than VEGF stimulation. Changes in expression of growth factors, matricellular proteins and matrix metalloproteinases in concert, diverge from direct pro-angiogenic paracrine mechanisms as a primary consequence of the used protocol. In vitro serum starvation (with or without VEGF present) appears to favour cardioprotection, extracellular matrix remodelling and blood vessel maturation relevant for the late maturation phase in infarct healing.
Myoblast-conditioned media improve regeneration and revascularization of ischemic muscles in diabetic mice
Authors: Kozakowska Magdalena , Kotlinowski Jerzy , Grochot-Przeczek Anna , Ciesla Maciej , Pilecki Bartosz , Derlacz Rafal , Dulak Jozef , Jozkowicz Alicja
Published: April 2015

Introduction

Diabetes is associated with reduced expression of heme oxygenase-1 (HO-1), a heme-degrading enzyme with cytoprotective and proangiogenic properties. In myoblasts and muscle satellite cells HO-1 improves survival, proliferation and production of proangiogenic growth factors. Induction of HO-1 in injured tissues facilitates neovascularization, the process impaired in diabetes. We aimed to examine whether conditioned media from the HO-1 overexpressing myoblast cell line can improve a blood-flow recovery in ischemic muscles of diabetic mice.

Methods

Analysis of myogenic markers was performed at the mRNA level in primary muscle satellite cells, isolated by a pre-plate technique from diabetic db/db and normoglycemic wild-type mice, and then cultured under growth or differentiation conditions. Hind limb ischemia was performed by femoral artery ligation in db/db mice and blood recovery was monitored by laser Doppler measurements. Mice were treated with a single intramuscular injection of conditioned media harvested from wild-type C2C12 myoblast cell line, C2C12 cells stably transduced with HO-1 cDNA, or with unconditioned media.

Results

Expression of HO-1 was lower in muscle satellite cells isolated from muscles of diabetic db/db mice when compared to their wild-type counterparts, what was accompanied by increased levels of Myf5 or CXCR4, and decreased Mef2 or Pax7. Such cells also displayed diminished differentiation potential when cultured in vitro, as shown by less effective formation of myotubes and reduced expression of myogenic markers (myogenic differentiation antigen - myoD, myogenin and myosin). Blood flow recovery after induction of severe hind limb ischemia was delayed in db/db mice compared to that in normoglycemic individuals. To improve muscle regeneration after ischemia, conditioned media collected from differentiating C2C12 cells (control and HO-1 overexpressing) were injected into hind limbs of diabetic mice. Analysis of blood flow revealed that media from HO-1 overexpressing cells accelerated blood-flow recovery, while immunohistochemical staining assessment of vessel density in injected muscle confirmed increased angiogenesis. The effect might be mediated by stromal-cell derived factor-1α proangiogenic factor, as its secretion is elevated in HO-1 overexpressing cells.

Conclusions

In conclusion, paracrine stimulation of angiogenesis in ischemic skeletal muscle using conditioned media may be a safe approach exploiting protective and proangiogenic properties of HO-1 in diabetes.
Mouse aorta-derived mesenchymal progenitor cells contribute to and enhance the immune response of macrophage cells under inflammatory conditions
Authors: Evans Jodi F , Salvador Veronica , George Sheela , Trevino-Gutierrez Cristina , Nunez Catherine
Published: April 2015

Introduction

Mesenchymal progenitor cells interact with immune cells and modulate inflammatory responses. The cellular characteristics required for this modulation are under fervent investigation. Upon interaction with macrophage cells, they can contribute to or suppress an inflammatory response. Current studies have focused on mesenchymal progenitors derived from bone marrow, adipose, and placenta. However, the arterial wall contains many mesenchymal progenitor cells, which during vascular disease progression have the potential to interact with macrophage cells. To examine the consequence of vascular-tissue progenitor cell-macrophage cell interactions in an inflammatory environment, we used a recently established mesenchymal progenitor cell line derived from the mouse aorta.

Methods

Mouse bone marrow-derived macrophage (MΦ) cells and mouse aorta-derived mesenchymal progenitor (mAo) cells were cultured alone or co-cultured directly and indirectly. Cells were treated with oxidized low-density lipoprotein (ox-LDL) or exposed to the inflammatory mediators lipopolysaccharide (LPS) and interferon-gamma (IFNγ) or both. A Toll-like receptor-4 (TLR4)-deficient macrophage cell line was used to determine the role of the mAo cells. To monitor inflammation, nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNFα) secretions were measured.

Results

Mesenchymal progenitor cells isolated from aorta and cloned by high proliferative capacity (mAo) can differentiate into multiple mesenchymal lineages and are positive for several commonly used mouse mesenchymal stem cell markers (that is, CD29, CD44, CD105, CD106, and Sca-1) but are negative for CD73 and ecto-5′-nucleotidase. In co-culture with MΦ cells, they increase MΦ oxidized-LDL uptake by 52.2%. In an inflammatory environment, they synergistically and additively contribute to local production of both NO and IL-6. After exposure to ox-LDL, the inflammatory response of MΦ cells to LPS and LPS/IFNγ is muted. However, when lipid-laden MΦ cells are co-cultured with mAo cell progenitors, the muted response is recovered and the contribution by the mAo cell progenitor is dependent upon cell contact.

Conclusions

The resident mesenchymal progenitor cell is a potential contributor to vascular inflammation when in contact with inflamed and lipid-laden MΦ cells. This interaction represents an additional target in vascular disease treatment. The potential for resident cells to contribute to the local immune response should be considered when designing therapeutics targeting inflammatory vascular disease.
A survey on security attacks and countermeasures with primary user detection in cognitive radio networks
Authors: Marinho José , Granjal Jorge , Monteiro Edmundo
Published: April 2015

Currently, there are several ongoing efforts for the definition of new regulation policies, paradigms, and technologies aiming a more efficient usage of the radio spectrum. In this context, cognitive radio (CR) emerges as one of the most promising players by enabling the dynamic access to vacant frequency bands on a non-interference basis. However, the intrinsic characteristic of CR opens new ways for attackers, namely in the context of the effective detection of incumbent or primary users (PUs), the most fundamental and challenging requirement for the successful operation of CR networks. In this article, we provide a global and integrated vision of the main threats affecting CR environments in the context of the detection of primary users, with a particular focus on spectrum sensing data falsification and primary user emulation attacks. We also address solutions and research challenges still required to address such threats. Our discussion aims at being complete and self-contained, while also targeting readers with no specific background on this important topic of CR environments. It is, as far as our knowledge goes, the first work providing a global and clear vision of security threats and countermeasures in the context of primary user detection in CR.
Gene expression in the liver of female, but not male mice treated with rapamycin resembles changes observed under dietary restriction
Authors: Yu Zhen , Sunchu Bharath , Fok Wilson C , Alshaikh Nahla , Pérez Viviana I
Published: April 2015

It is well known that in mice the extension in lifespan by rapamycin is sexually dimorphic, in that it has a larger effect in females than males. In a previous study we showed that in male C57BL6 mice, rapamycin had less profound effects in both gene expression and liver metabolites when compared to dietary restriction (DR), but no data was available in females. Because recent studies showed that rapamycin increases longevity in a dose dependent manner and at every dose tested the effect remains larger in females than in males, we hypothesized that rapamycin should have a stronger effect on gene expression in females, and this effect could be dose dependent. To test this hypothesis, we measured the changes in liver gene expression induced by rapamycin (14 ppm) with a focus on several genes involved in pathways known to play a role in aging and that are altered by DR. To investigate whether any effects are dose dependent, we also analyzed females treated with two additional doses of rapamycin (22 and 42 ppm). We observed striking differences between male and female in gene expression at 14 ppm, where females have a larger response to rapamycin than males, and the effects of rapamycin in females resemble what we observed under DR. However, these effects were generally not dose dependent. These data support the notion that female mice respond better to rapamycin, and at least with the set of genes studied here, the effect of rapamycin in females resemble the effect of DR.
Depression and anxiety in expectant and new fathers: longitudinal findings in Australian men
Authors: Leach Liana S. , Mackinnon Andrew , Poyser Carmel , Fairweather-Schmidt A. Kate
Published: April 2015

Background

Despite growing interest in men's perinatal mental health, we still know little about whether becoming a new father is associated with increases in psychological distress.

Aims

To use prospective longitudinal data to investigate whether becoming a first-time expectant (partner pregnant) and/or new father (child <1 year) is associated with increases in depression and anxiety.

Method

Men were aged 20–24 years at baseline (n= 1162). Levels of depression and anxiety were measured at four time points over 12 years. Over this time, 88 men were expectant fathers, 108 men were new fathers and 626 men remained non-fathers.

Results

Longitudinal mixed models showed no significant increase in depression or anxiety as a function of expectant or new fatherhood, as compared with pre-fatherhood levels.

Conclusions

Our findings suggest that, generally, expectant and new fathers are not at greater risk of depression or anxiety. Future epidemiological research should continue to identify men who are most (and least) at risk to focus resources and assistance most effectively.
On Not Betraying Poetry
Authors: Farber Jerry
Published: April 2015

Responding to evidence of a steep decline in the reading of poetry, this article advocates a set of broad principles for poetry teaching that address the aesthetic function and materiality of poetry, and argues for a dialectic relationship in the poetry classroom between thoughtful analysis and interpretive freedom.
Small College, World Literature
Authors: Landry Travis , Matz Jesse
Published: April 2015

Now that “world literature” has become a theoretical problem as much as a body of texts, the small-college classroom faces new challenges and new opportunities. Resource limitations and other constraints combine with advantages of scale and ethos to make the small college a special proving ground for world-literature pedagogy.
Mule Bone 2.0
Authors: Christian Shawn Anthony
Published: April 2015

This essay, focusing on Zora Neale Hurston and Langston Hughes’s 1930 play and infamous literary collaboration, explores the possibilities of combining new digital tools with traditional scholarly approaches to better understand how the multilayered racial discourse of African American literature in the early twentieth century informs this signal collaboration. Moreover, Christian outlines the benefits of including African American literature in digital humanities projects.
Case Report: A case of neurogenic bladder in the setting of Behçet's disease after an initial diagnosis of multiple sclerosis
Authors: Pastuszak Alexander W , Boone Timothy B.
Published: April 2015

Behçet’s disease (BD) is an autoimmune vasculitis with an unclear etiology presenting with a classic triad of symptoms including oral and genital ulcers as well as iridocyclitis. A subset of BD patients exhibit neurological symptoms including psychiatric disturbances, balance problems, and voiding dysfunction, and the symptoms of BD can mimic other neurological diseases, including multiple sclerosis (MS).  Differentiating between potential diagnoses is challenging due to the lack of specific tests for these disorders and the overlap between clinical symptoms and radiological findings. We describe the case of a 52 year old woman initially diagnosed with and treated for MS.  From the urologic standpoint, she was treated for neurogenic detrusor overactivity with detrusor-sphincter-dyssynergia utilizing ileocecal augmentation cystoplasty with a continent stoma for intermittent catheterization. The patient was later diagnosed with BD in light of additional clinical findings.
Use of Insurance Against a Small Loss as an Incentive Strategy
Authors: Meeker Daniella , Thompson Christin , Strylewicz Greg , Knight Tara K. , Doctor Jason N.
Published: April 2015

The success of extended warranties and buyer protection plans suggests that insurance against a small loss has high decision utility. We explore whether the behavioral insight that people are highly averse to small chances of loss can be used to create a powerful incentive that has very low expected value. We compare decisions of individuals offered fixed payments for healthy choices to those offered insurance in exchange for healthy choices. We test the prediction that aversion to small losses will result in very high rates of health behavior uptake in exchange for insurance. Three hundred participants endowed with a $2 bonus randomly received one of two incentives for completing a scheduled health risk assessment: (1) an insurance guarantee against the 1% risk of losing the $2 bonus or (2) a fixed payment at the expected value of the insurance. Relative to the fixed payment condition, participants in the insurance intervention were 70% more likely to meet their health risk assessment appointment (p < 0.01). Fixed payments of $2.59 were needed for every $1 spent on insurance to achieve the same behavioral effect. Loss aversion, probability weighting, and the certainty effect may account for this result. Incentive design may benefit from utilizing an insurance paradigm.
The Impact of Budget Constraints on Flexible vs. Dedicated Technology Choice
Authors: Boyabatlı Onur , Leng Tiecheng , Toktay L. Beril
Published: April 2015

This paper studies the flexible versus dedicated technology choice and capacity investment decisions of a multiproduct firm under demand uncertainty in the presence of budget constraints. The firm operates under a capital budget for financing the capacity investment, and an operating budget, which is uncertain in the capacity investment stage, for financing the production. We investigate how the tightening of the capital budget and a lower financial flexibility in the production stage (the likelihood of having a sufficient operating budget) shape the optimal technology choice. We find that the dominant regime is one where dedicated technology should be adopted for a larger investment cost range, and thus, is the best response to the tighter capital budget, whereas flexible technology is the best response to lower financial flexibility. We identify the key roles that the capacity intensity (the ratio of unit capacity cost to total unit capacity and production cost) of each technology and the pooling value of operating budget with dedicated technology, which brings this technology closer to flexible technology in terms of the resource network’s flexibility, play in a budget-constrained environment. Managerially, our results underline that in the presence of financial constraints, firms should manage technology adoption together with plant location, which shapes capacity intensity, or product portfolio, which shapes financial flexibility.

This paper was accepted by Serguei Netessine, operations management.