bluuebunny/crossref_metadata_2025 huggingface dataset:
Pushing the Paradigm
Authors: Jayawardene Sureshi
Published: October 2013

This study locates the scholarship on the Siddis of India and the Kaffirs of Sri Lanka—two Africana communities in the Indian Ocean. Using Afrocentric theories and concepts, this study interrogates the limitations of extant scholarship on the Siddis and Kaffirs using a content analysis of select scholarly texts. Through this content analysis, the discursive decentralization of the history, culture, perspectives, and experiences of the Siddis and Kaffirs submerged in Eurocentric and multicultural narratives of African presence in India and Sri Lanka is revealed. This study establishes typologies of the dominant discursive approaches that scholars are using to study the Siddis and Kaffirs. In uncovering these typologies, this study emphasizes the importance of a culturally grounded worldview, methodological framework, and scholarly location for the accurate and complete study and theorization about Africana people in the Indian Ocean region.
How Do Peer Coaches Improve Diabetes Care for Low-Income Patients?
Authors: Goldman Matthew L. , Ghorob Amireh , Eyre Stephen L. , Bodenheimer Thomas
Published: October 2013

Purpose

The purpose of the study was to explore the perspectives and roles of peer coaches, who are patients with diabetes trained to provide diabetes self-management support (DSMS) to other patients.

Methods

A focus group and 17 qualitative semi-structured interviews were conducted with community-based peer coaches in San Francisco in order to better understand the process by which these coaches engaged with their patients. Transcripts were coded and analyzed using methods based on grounded theory to develop a theoretical model of peer coach roles.

Results

Peer coaches play 3 principal roles in providing DSMS: advisor, supporter, and role model. While working with patients, peer coaches had different approaches to setting emotional boundaries and to allocating responsibility for implementing health behavior changes. Peer coaches were more consistent in how they sought resources from providers. Peer coaches also became empowered to better manage their own diabetes.

Conclusion

Peer coaches are a highly motivated potential workforce uniquely positioned to teach and empower patients by building trust through shared experiences. The variability in coaching styles suggests an inherent diversity among peer coaches that must be accounted for in future strategies for design, recruitment, training, and oversight of peer coaching programs.
Surviving Divorce
Authors: Hansson Leeni , Laidmäe Virve-Ines
Published: October 2013

The objective of the article is to analyze how divorced women construct their postdivorce status and describe ways of overcoming divorce and finding new meaning in life. The interviewees were people whose identity as married women had been largely based on the celebrity status of their ex-husbands. The analysis of interview material published in Eesti Naine ( Estonian Woman) from the mid-1980s to the early 2000s demonstrates that the approach toward the subject of divorce has changed considerably—from ignoring it in the 1980s to outspoken stories including full names in the second half of the 1990s. The study indicated that divorced women interviewed for the magazine reconstructed their postdivorce identities by using three main types of narrative—success stories, sad stories, and stories constructed around postdivorce parenthood. Our study suggests that there is interplay between changes in the social context and attitudes toward divorce and postdivorce status.
Crossing Methodological Borders
Authors: Stanton Christine Rogers
Published: October 2013

To advance socially just research, scholars—including those who utilize qualitative methodologies—must confront the colonizing reputation that frames such work in Indigenous communities. This article explores the potential for Community-Based Participatory Research to guide the re-envisioning of mainstream conceptions of scholarly control to cross epistemological borders between theory and practice. A project that endeavored to engage Native participants throughout the research process provides context for the discussion of ongoing challenges and emerging possibilities. This work holds implications for participatory research design and implementation in cross-cultural contexts, especially as connected to shifting decolonizing theory to practice.
Development and validation of a patient satisfaction questionnaire for outpatients attending health centres in North Indian cities
Authors: Goel Sonu , Sharma Deepak , Singh Amarjeet
Published: October 2013

Objectives

With the mandate of the Indian Government to improve health services for the population, improving patients’ satisfaction with outpatient department (OPD) services is vital. Many scales developed in Western societies to assess patient satisfaction may not be appropriate to the Indian health care system. The aim of this study was to develop and conduct initial psychometric testing of a satisfaction questionnaire for patients attending OPDs in North India.

Methods

The North India Outpatient Department Satisfaction Scale (NIOPDSS) was initially constructed based on a Delphi consensus among experts. After pretesting on a small number of patients, a cross-sectional survey was conducted among 942 outpatients in Chandigarh, North India. The psychometric properties of the questionnaire in terms of content validity, construct validity, convergent and discriminant validity, and reliability were assessed.

Results

Eighty items were generated from the Delphi exercise. After assessing the content validity, data quality and construct validity of the questionnaire, a final instrument with 17 items representing six dimensions of patient satisfaction was developed. The internal consistency ranged from 0.72 to 0.93 and intra-class correlation coefficient ranged from 0.52 to 0.80.

Conclusion

NIOPDSS appears to be a reliable and valid measure of patient satisfaction for patients attending OPDs in North India. Further research should be carried out with different outpatient populations to assess the wider performance of the questionnaire.
Making Hay While the Sun Shines
Authors: van der Pas Daphne
Published: October 2013

When do parties take over the media’s issue attention in parliament? Scholarly work has shown that the mass media’s influence over the political agenda is conditional, yet only recently scholars started to consider the active role of parties and their strategic incentives in responding to the media. This article argues that parties only respond to media attention if the issue is framed in the party’s terms, as the right framing helps the party attain its policy goals. This argument is supported by pooled time-series analyses of the issue of European integration and the issue of immigration in Sweden and the Netherlands over the period 1995 to 2010. Altogether, the study contributes to our understanding of the strategic incentives and options parties have in responding to the media, as well as to our knowledge of the role of framing in political competition.
Elbow Injuries in Youth Baseball Players Without Prior Elbow Pain
Authors: Matsuura Tetsuya , Suzue Naoto , Kashiwaguchi Shinji , Arisawa Kokichi , Yasui Natsuo
Published: October 2013

Background:

Many risk factors for throwing injuries have been proposed. However, little is known about the risk factors for elbow injuries, particularly on physeal injuries in youth baseball players without prior elbow pain.

Purpose:

To investigate the risk factors for elbow injuries with a focus on physeal injuries that could predispose youth baseball players without elbow pain to elbow injuries.

Study Design:

A prospective epidemiology study.

Methods:

In 2006, 449 players without prior elbow pain were observed prospectively for 1 season to study injury incidence in relation to specific risk factors. The average age was 10.1 years (range, 7-11 years). One year later, all players were examined by administering a questionnaire, physical examination, and radiographic examination. Data for the groups with and without elbow pain were analyzed using multivariate logistic regression models.

Results:

Among the 449 participants, 30.5% reported episodes of elbow pain during the season. Of the players who reported elbow pain, 72.3% presented abnormal findings on physical examination, and of those players, 81.4% had radiographic abnormalities. Multivariate analysis showed that the age of 12 years (at 1-year examination), pitcher and catcher positions, and playing more than 100 games per year were risk factors for elbow pain.

Conclusion:

It is expected that 30% of youth baseball players have elbow pain each year, and nearly 60% of players with elbow pain exhibit radiographic abnormalities. The age of 12 years, pitcher and catcher positions, and playing more than 100 games per year are risk factors for elbow pain.
Leukemia cell–targeted STAT3 silencing and TLR9 triggering generate systemic antitumor immunity
Authors: Hossain Dewan Md Sakib , Dos Santos Cedric , Zhang Qifang , Kozlowska Anna , Liu Hongjun , Gao Chan , Moreira Dayson , Swiderski Piotr , Jozwiak Agnieszka , Kline Justin , Forman Stephen , Bhatia Ravi , Kuo Ya-Huei , Kortylewski Marcin
Published: October 2013

Key Points

Blocking STAT3 in acute myeloid leukemia cells stimulates their TLR9-induced immunogenicity and antigen-specific activation of CD8+ T cells. Systemic delivery of CpG-Stat3 siRNA generates potent adaptive immune responses eradicating disseminated acute myeloid leukemia in vivo.
Giant mesenteric hemangioma of cavernous and venous mixed type: a rare case report
Authors: Yang Guang-Zhi , Li Jing , Jin Hua
Published: October 2013

Background

Although vascular tumours are one of the most common soft tissue neoplasms, those occurring in the gastrointestinal system are rare and cases involving mesentery are even further rare. Herein, we reported a rare case of giant hemangioma in mesentery of the small bowel.

Case presentation

A 5-year-old girl was admitted to the emergency room with abdominal pain and vomit for two days. Ultrasonography and computed tomography showed a giant solid-cystic abdominal mass, preferring diagnosis of teratoma. A large neoplasm in the mesentery of the small bowel was found in the surgical exploration, which was then resected with the partial bowel. A brown honeycomb mass in size 16 cm×8 cm×5 cm was observed to adhere to the small bowel, and diagnosed as hemangioma of cavernous and venous mixed type in final pathology.

Conclusion

The mesenteric hemangioma is extremely rare and the variable imaging tests are non-specific, thus the diagnosis is rarely made before surgery and usually established by histopathological investigation after surgery. So the mesenteric hemangioma is supposed to be differentiated in abdominal mass, either in adults or children. Complete surgical resection is the optimal treatment.
Strategies for the multiplex mapping of genes to traits
Authors: Garst Andrew , Lynch Michael , Evans Ron , Gill Ryan T
Published: October 2013

Rewiring and optimization of metabolic networks to enable the production of commercially valuable chemicals is a central goal of metabolic engineering. This prospect is challenged by the complexity of metabolic networks, lack of complete knowledge of gene function(s), and the vast combinatorial genotype space that is available for exploration and optimization. Various approaches have thus been developed to aid in the efficient identification of genes that contribute to a variety of different phenotypes, allowing more rapid design and engineering of traits desired for industrial applications. This review will highlight recent technologies that have enhanced capabilities to map genotype-phenotype relationships on a genome wide scale and emphasize how such approaches enable more efficient design and engineering of complex phenotypes.
A country bug in the city: urban infestation by the Chagas disease vector Triatoma infestans in Arequipa, Peru
Authors: Delgado Stephen , Ernst Kacey C , Pumahuanca María Luz Hancco , Yool Stephen R , Comrie Andrew C , Sterling Charles R , Gilman Robert H , Náquira César , Levy Michael Z ,   the Chagas Disease Working Group in Arequipa, Peru
Published: October 2013

Background

Interruption of vector-borne transmission of Trypanosoma cruzi remains an unrealized objective in many Latin American countries. The task of vector control is complicated by the emergence of vector insects in urban areas.

Methods

Utilizing data from a large-scale vector control program in Arequipa, Peru, we explored the spatial patterns of infestation by Triatoma infestans in an urban and peri-urban landscape. Multilevel logistic regression was utilized to assess the associations between household infestation and household- and locality-level socio-environmental measures.

Results

Of 37,229 households inspected for infestation, 6,982 (18.8%; 95% CI: 18.4 – 19.2%) were infested by T. infestans. Eighty clusters of infestation were identified, ranging in area from 0.1 to 68.7 hectares and containing as few as one and as many as 1,139 infested households. Spatial dependence between infested households was significant at distances up to 2,000 meters. Household T. infestans infestation was associated with household- and locality-level factors, including housing density, elevation, land surface temperature, and locality type.

Conclusions

High levels of T. infestans infestation, characterized by spatial heterogeneity, were found across extensive urban and peri-urban areas prior to vector control. Several environmental and social factors, which may directly or indirectly influence the biology and behavior of T. infestans, were associated with infestation. Spatial clustering of infestation in the urban context may both challenge and inform surveillance and control of vector reemergence after insecticide intervention.
Prostaglandin F2α FP receptor antagonist improves outcomes after experimental traumatic brain injury
Authors: Glushakov Alexander V , Robbins Sean W , Bracy Connor L , Narumiya Shuh , Doré Sylvain
Published: October 2013

Background

Injuries to the brain promote upregulation of prostaglandins, notably the proinflammatory PGF2α, and overactivation of their cognate G-protein-coupled FP receptor, which could exacerbate neuronal damage. Our study is focused on investigation of the FP receptor as a target for novel neuroprotective drugs in a preclinical animal traumatic brain injury (TBI) model.

Methods

Accordingly, the effects of acute intraperitoneal post-treatment with selective FP antagonist AL-8810 were studied in wildtype (WT) and FP receptor knockout (FP-/-) mice after controlled cortical impact (CCI). Neurological impairments were evaluated using neurological deficit scores (NDS) and the grip strength test. Cortical lesions and overall brain pathology were assessed using immunohistochemistry.

Results

Morphological analyses of cerebral vasculature and anastomoses revealed no differences between WT and FP-/- mice. CCI produced cortical lesions characterized by cavitation, neuronal loss, and hematoma with a volume of 20.0 ± 1.0 mm3 and significant hippocampal swelling (146.5 ± 7.4% of contralateral) compared with sham (P < 0.05). Post-treatment with AL-8810 (1 to 10 mg/kg) had no significant effect on cortical lesions, which suggests the irreversible effect of primary CCI injury, but significantly reduced hippocampal swelling to a size not significantly different from the sham group. Post-treatment with AL-8810 at a dose of 10 mg/kg significantly improved NDS at 24 and 48 hours after CCI (P < 0.001 and P < 0.01, respectively). In the AL-8810 group, CCI-induced decrease in grip strength was three-fold (2.93 ± 1.71) less and significantly different than in the saline-treated group. The FP-/- mice had significantly less hippocampal swelling, but not NDS, compared with WT mice. In addition, immunohistochemistry showed that pharmacologic blockade and genetic deletion of FP receptor led to attenuation of CCI-induced gliosis and microglial activation in selected brain regions.

Conclusion

This study provides, for the first time, demonstration of the unique role of the FP receptor as a potential target for disease-modifying CNS drugs for treatment of acute traumatic injury.
Endophytic fungi from the Amazonian plant Paullinia cupana and from Olea europaea isolated using cassava as an alternative starch media source
Authors: Sia Eliandra de Freitas , Marcon Joelma , Luvizotto Danice Mazzer , Quecine Maria Carolina , Tsui Sarina , Pereira José Odair , Pizzirani-Kleiner Aline Aparecida , Azevedo João Lúcio
Published: October 2013

Endophytic fungi live inside plants, apparently do not cause any harm to their hosts and may play important roles in defense and growth promotion. Fungal growth is a routine practice at microbiological laboratories, and the Potato Dextrose Agar (PDA) is the most frequently used medium because it is a rich source of starch. However, the production of potatoes in some regions of the world can be costly. Aiming the development of a new medium source to tropical countries, in the present study, we used leaves from the guarana (a tropical plant from the Amazon region) and the olive (which grows in subtropical and temperate regions) to isolate endophytic fungi using PDA and Manihot Dextrose Agar (MDA). Cassava (Manihot esculenta) was evaluated as a substitute starch source. For guarana, the endophytic incidence (EI) was 90% and 98% on PDA and MDA media, respectively, and 65% and 70% for olive, respectively. The fungal isolates were sequenced using the ITS- rDNA region. The fungal identification demonstrated that the isolates varied according to the host plant and media source. In the guarana plant, 13 fungal genera were found using MDA and six were found using PDA. In the olive plant, six genera were obtained using PDA and 4 were obtained using MDA. The multivariate analysis results demonstrated the highest fungal diversity from guarana when using MDA medium. Interestingly, some genera were isolated from one specific host or in one specific media, suggesting the importance of these two factors in fungal isolation specificity. Thus, this study indicated that cassava is a feasible starch source that could serve as a potential alternative medium to potato medium.
Skeletal Actions of Fasting-Induced Adipose Factor (FIAF)
Authors: Lin Jian-ming , Naot Dorit , Watson Maureen , Costa Jessica L. , Reid Ian R. , Cornish Jillian , Grey Andrew
Published: October 2013

Several adipokines are known to influence skeletal metabolism. Fasting-induced adipose factor (FIAF) is an adipokine that gives rise to 2 further peptides in vivo, the N-terminal coiled-coil domain (FIAFCCD) and C-terminal fibrinogen-like domain (FIAFFLD). The skeletal action of these peptides is still uncertain. Our results show that FIAFCCD is a potent inhibitor of osteoclastogenesis and function, as seen in mouse bone marrow and RAW264.7 cell cultures, and in a resorption assay using isolated primary mature osteoclasts. The inhibitory effects at 500 ng/mL were approximately 90%, 50% and 90%, respectively, in these assays. FIAFCCD also stimulated osteoblast mitogenesis by approximately 30% at this concentration. In comparison, FIAFFLD was only active in decreasing osteoblast mitogenesis, and intact FIAF had no effect in any of these assays. In murine bone marrow cultures, FIAFCCD reduced the expression of macrophage colony-stimulating factor (M-CSF), nuclear factor of activated T-cells c1 (NFATc1) and dendritic cell-specific transmembrane protein (DC-STAMP), and to lesser extent suppressed the expression of connective tissue growth factor (CTGF). FIAFCCD also decreased expression of M-CSF and CTGF in stromal/osteoblastic ST2 cells. Its effect on receptor activator of nuclear factor κB (RANKL) and osteoprotegerin expression in bone marrow was not consistent with its inhibitory action on osteoclastogenesis, but it decreased RANKL expression in ST2 cells. In RAW264.7 cell cultures, FIAFCCD significantly reduced the expression of NFATc1 and DC-STAMP. In conclusion, FIAFCCD inhibits osteoclast differentiation and function in vitro and decreases expression of genes encoding key osteoclastogenic factors such as M-CSF, CTGF, NFATc1, and DC-STAMP. FIAFCCD's action on osteoclasts may be independent of the RANKL/osteoprotegerin pathway. These results suggest a novel mechanism by which adipose tissue may regulate bone resorption and skeletal health.
Lactational Anovulation in Mice Results From a Selective Loss of Kisspeptin Input to GnRH Neurons
Authors: Liu X. , Brown R.S.E. , Herbison A.E. , Grattan D.R.
Published: October 2013

In mammals, lactation is associated with a period of infertility characterized by the loss of pulsatile secretion of GnRH and cessation of ovulatory cycles. Despite the importance of lactational infertility in determining overall fecundity of a species, the mechanisms by which the suckling stimulus suppresses GnRH secretion remain unclear. Because kisspeptin neurons are critical for fertility, the aim of this study was to test the hypothesis that reduced kisspeptin expression might mediate the lactation-induced suppression of fertility, using mouse models. In the rostral periventricular area of the third ventricle (RP3V), a progressive decrease in RP3V Kiss1 mRNA levels was observed during pregnancy culminating in a 10-fold reduction during lactation compared with diestrous controls. This was associated with approximately 60% reduction in the numbers of kisspeptin-immunoreactive neurons in the RP3V detected during lactation. Similarly, in the arcuate nucleus there was also a significant decrease in Kiss1 mRNA levels during late pregnancy and midlactation, and a notable decrease in kisspeptin fiber density during lactation. The functional characteristics of the RP3V kisspeptin input to GnRH neurons were assessed using electrophysiological approaches in an acute brain slice preparation. Although endogenous RP3V kisspeptin neurons were found to activate GnRH neurons in diestrous mice, this was never observed during lactation. This did not result from an absence of kisspeptin receptors because GnRH neurons responded normally to 100 nM exogenous kisspeptin during lactation. The kisspeptin deficit in lactating mice was selective, because GnRH neurons responded normally to RP3V gamma aminobutryic acid inputs during lactation. These data demonstrate that a selective loss of RP3V kisspeptin inputs to GnRH neurons during lactation is the likely mechanism causing lactational anovulation in the mouse.
IL-15 Is Required for Postexercise Induction of the Pro-Oxidative Mediators PPARδ and SIRT1 in Male Mice
Authors: Quinn LeBris S. , Anderson Barbara G. , Conner Jennifer D. , Wolden-Hanson Tami , Marcell Taylor J.
Published: October 2013

Physical exercise induces transient upregulation of the pro-oxidative mediators peroxisome proliferator-activated receptor-δ (PPARδ), silent information regulator of transcription (sirtuin)-1 (SIRT1), PPARγ coactivator 1α (PGC-1α), and PGC-1β in skeletal muscle. To determine the role of the cytokine IL-15 in acute postexercise induction of these molecules, expression of these factors after a bout of exhaustive treadmill running was examined in the gastrocnemius muscle of untrained control and IL-15–knockout (KO) mice. Circulating IL-15 levels increased transiently in control mice after exercise. Control mice, but not IL-15–KO mice, upregulated muscle PPARδ and SIRT1 protein after exercise, accompanied by a complex pattern of mRNA expression for these factors. However, in exhaustive exercise, control mice ran significantly longer than IL-15–KO mice. Therefore, in a second experiment, mice were limited to a 20-minute run, after which a similar pattern of induction of muscle PPARδ and SIRT1 protein by control mice only was observed. In a separate experiment, IL-15–KO mice injected systemically with recombinant IL-15 upregulated muscle PPARδ and SIRT1 mRNA within 30 minutes and also exhibited increased muscle PPARδ protein levels by 3 hours. After exercise, both control and IL-15–KO mice downregulated IL-15 receptor-α (IL-15Rα) mRNA, whereas IL-15Rα–deficient mice exhibited constitutively elevated circulating IL-15 levels. These observations indicate IL-15 release after exercise is necessary for induction of PPARδ and SIRT1 at the protein level in muscle tissue and suggest that exercise releases IL-15 normally sequestered by the IL-15Rα in the resting state. These findings could be used to develop an IL-15–based strategy to induce many of the metabolic benefits of physical exercise.
Perfluorooctanesulfonate (PFOS) Perturbs Male Rat Sertoli Cell Blood-Testis Barrier Function by Affecting F-Actin Organization via p-FAK-Tyr407: An in Vitro Study
Authors: Wan Hin-Ting , Mruk Dolores D. , Wong Chris K. C. , Cheng C. Yan
Published: October 2013

Environmental toxicants such as perfluorooctanesulfonate (PFOS) have been implicated in male reproductive dysfunction, including reduced sperm count and semen quality, in humans. However, the underlying mechanism(s) remains unknown. Herein PFOS at 10–20 μM (∼5–10 μg/mL) was found to be more potent than bisphenol A (100 μM) in perturbing the blood-testis barrier (BTB) function by disrupting the Sertoli cell tight junction-permeability barrier without detectable cytotoxicity. We also delineated the underlying molecular mechanism by which PFOS perturbed Sertoli cell BTB function using an in vitro model that mimics the BTB in vivo. First, PFOS perturbed F-actin organization in Sertoli cells, causing truncation of actin filaments at the BTB. Thus, the actin-based cytoskeleton was no longer capable of supporting the distribution and/or localization of actin-regulatory and adhesion proteins at the cell-cell interface necessary to maintain BTB integrity. Second, PFOS was found to perturb inter-Sertoli cell gap junction (GJ) communication based on a dye-transfer assay by down-regulating the expression of connexin-43, a GJ integral membrane protein. Third, phosphorylated focal adhesion kinase (FAK)-Tyr407 was found to protect the BTB from the destructive effects of PFOS as shown in a study via an overexpression of an FAK Y407E phosphomimetic mutant. Also, transfection of Sertoli cells with an FAK-specific microRNA, miR-135b, to knock down the expression of phosphorylated FAK-Tyr407 was found to worsen PFOS-mediated Sertoli cell tight junction disruption. In summary, PFOS-induced BTB disruption is mediated by down-regulating phosphorylated FAK-Tyr407 and connexin-43, which in turn perturbed F-actin organization and GJ-based intercellular communication, leading to mislocalization of actin-regulatory and adhesion proteins at the BTB.
Mechanisms of Palmitate-Induced Lipotoxicity in Human Osteoblasts
Authors: Gunaratnam Krishanthi , Vidal Christopher , Gimble Jeffrey M. , Duque Gustavo
Published: October 2013

The interest in the relationship between fat and bone has increased steadily during recent years. Fat could have a lipotoxic effect on bone cells through the secretion of fatty acids. Palmitate is the most prevalent fatty acid secreted by adipocytes in vitro. Considering that palmitate has shown a high lipotoxic effect in other tissues, here we characterized the lipotoxic effect of palmitate on human osteoblasts (Obs). Initially we tested for changes in palmitoylation in this model. Subsequently we compared the capacity of Obs to differentiate and form bone nodules in the presence of palmitate. From a mechanistic approach, we assessed changes in nuclear activity of β-catenin and runt-related transcription factor 2 (Runx2)/phosphorylated mothers against decapentaplegic (Smad) complexes using Western blotting and confocal microscopy. Quantitative real-time PCR showed negative changes in gene expression of palmitoyltransferase genes. Furthermore, palmitate negatively affected differentiation and bone nodule formation and mineralization by Obs. Although the expression of β-catenin in palmitate-treated cells was not affected, there was a significant reduction in the transcriptional activities of both β-catenin and Runx2. Confocal microscopy showed that whereas Runx2 and Smad-4 and -5 complex formation was increased in bone morphogenetic protein-2-treated cells, palmitate had a negative effect on protein expression and colocalization of these factors. In summary, in this study we identified potential mechanisms of palmitate-induced lipotoxicity, which include changes in palmitoylation, defective mineralization, and significant alterations in the β-catenin and Runx2/Smad signaling pathways. Our evidence facilitates the understanding of the relationship between fat and bone and could allow the development of new potential therapies for osteoporosis in older persons.
Effects of Estrogen on Bone mRNA Levels of Sclerostin and Other Genes Relevant to Bone Metabolism in Postmenopausal Women
Authors: Fujita Koji , Roforth Matthew M. , Demaray Susan , McGregor Ulrike , Kirmani Salman , McCready Louise K. , Peterson James M. , Drake Matthew T. , Monroe David G. , Khosla Sundeep
Published: October 2013

Context:

Studies in postmenopausal women have shown that estrogen reduces circulating sclerostin levels, but effects of estrogen on skeletal sclerostin mRNA levels are unknown.

Objective:

The objective of the study was to evaluate the effects of short-term estrogen treatment on bone mRNA levels of sclerostin and other genes relevant to bone metabolism.

Design, Setting, and Patients:

Needle bone biopsies were obtained from 20 postmenopausal women treated with transdermal estrogen for 3 weeks and 20 untreated controls. Quantitative PCR analyses were used to examine the expression of sclerostin and other genes related to bone metabolism, including 71 additional genes linked to bone density/fracture from genome-wide association studies.

Results:

Estrogen treatment was associated with lower bone sclerostin mRNA levels (by 48%, P < .05) and with lower (by 54%, P < .01) mRNA levels of the sclerostin-related protein, sclerostin domain-containing protein 1 (SOSTDC1), which is also a Wnt/bone morphogenetic protein inhibitor. Consistent with studies in mice showing that ovariectomy increased nuclear factor-κB (NF-κB) activation, we found that estrogen treatment was associated with a significant reduction in inflammatory genes as a group (P = .028), with bone mRNA levels of NFKB2 and RELB (both encoding proteins in the NF-κB transcription factor complex) being significantly reduced individual genes. Eight of the 71 genome-wide association study-related genes examined were modulated by estrogen (P < .05, false discovery rate < 0.10).

Conclusion:

In humans, estrogen-induced decreases in two key inhibitors of Wnt/bone morphogenetic protein signaling, sclerostin and SOSTDC1, along with reductions in NF-κB signaling, may be responsible for at least part of the protective effects of estrogen on bone.
A mechanistic‐based framework to understand how dissolved organic carbon is processed in a large fluvial lake
Authors: Massicotte Philippe , Frenette Jean‐Jacques
Published: October 2013

Lay Abstract

Dissolved organic carbon (DOC) is a fundamental component of the biogeochemical cycling of nutrients in aquatic ecosystems and is the main carbon source supporting bacterial production. The efficiency at which heterotrophic (nonphotosynthetic) bacteria convert this substrate into biomass depends mainly on the quality of DOC in the water column. DOC is constantly processed through various physical, chemical, and biological mechanisms that operate simultaneously and alter its quality. It is paramount to understand how these different processes interact to drive the fate of DOC in aquatic ecosystems. Based on field data collected in a large fluvial lake, we developed and validated a mechanistic model that provides a framework to understand the relative contribution of the main processes involved in both labile (DOCL) and semilabile (DOCSL) DOC pool kinetics. The model revealed that during the downstream flow, each category of DOC pool was processed differently by bacteria: DOCL was preferentially used for biomass production, whereas DOCSL completed bacterial carbon demand. Our results also suggest that a decrease in DOCL abundance will further determine the intake of DOCSL.
Meeting report – TGF-β superfamily: signaling in development and disease
Authors: Zhang Ying E. , Newfeld Stuart J.
Published: October 2013

The latest advances on the transforming growth factor β (TGF-β) and bone morphogenetic protein (BMP) signaling pathways were reported at the July 2013 FASEB Summer Research Conference ‘The TGF-β Superfamily: Development and Disease’. The meeting was held in Steamboat Springs, Colorado, USA at 6700 feet above sea level in the Rocky Mountains. This was the seventh biannual meeting in the series. In attendance were investigators from a broad range of disciplines with a common interest in the mechanics of TGF-β and BMP signaling pathways, their normal developmental and homeostatic functions, and the diseases associated with pathway misregulation.
Moments Tensors, Hilbert's Identity, and k-wise Uncorrelated Random Variables
Authors: Jiang Bo , He Simai , Li Zhening , Zhang Shuzhong
Published: October 2013

In this paper, we introduce a notion to be called k-wise uncorrelated random variables, which is similar but not identical to the so-called k-wise independent random variables in the literature. We show how to construct k-wise uncorrelated random variables by a simple procedure. The constructed random variables can be applied, e.g., to express the quartic polynomial (xTQx)2, where Q is an n × n positive semidefinite matrix, by a sum of fourth powered polynomial terms, known as Hilbert's identity. By virtue of the proposed construction, the number of required terms is no more than 2n4 + n. This implies that it is possible to find a (2n4 + n)-point distribution whose fourth moments tensor is exactly the symmetrization of Q ⊗ Q. Moreover, we prove that the number of required fourth powered polynomial terms to express (xTQx)2 is at least n(n + 1)/2. The result is applied to prove that computing the matrix 2 ↦ 4 norm is NP-hard. Extensions of the results to complex random variables are discussed as well.
The hills are alive with … My Songs, My Dreams? The Sound of Music in Germany and Austria
Authors: Jubin Olaf
Published: October 2013

Robert Wise’s 1965 screen version of Rodgers and Hammerstein’s The Sound of Music was one of the biggest blockbusters in Hollywood history: in the United States alone it had box-office takings of $1.16 billion (adjusted for inflation). It was a smash hit and became an important pop-cultural reference point in countless other countries around the world. But, to the utter surprise and dismay of film distributor 20th Century Fox, The Sound of Music failed to win over audiences in the very territory in which the story was set. In fact, the ‘Best Picture’ Oscar winner of 1965 was such a flop in Germany and Austria as My Songs, My Dreams (English translation of the German title) that it did not even recoup its dubbing costs. To this day, the film remains virtually unknown in either country. This article investigates several potential reasons why the film never ‘clicked’ with Germans and Austrians, such as the popularity of two earlier German films about the Trapp family singers, the 1956 movie Die Trapp-Familie and its 1958 sequel Die Trapp-Familie in Amerika. It also considers the US film’s portrayal of fascism and its inauthentic depiction of Austria and Austrian culture. Other factors that might have been crucial in the reception of My Songs, My Dreams include local reviews, the advertising for the film, the German dubbing and the general disinterest of Austrian and German audiences in Hollywood musicals.
Operetta beyond borders: The different versions of Die Csárdásfürstin in Europe and the United States (1915–1921)
Authors: Imre Zoltán
Published: October 2013

Imre Kálmán’s operetta Die Csárdásfürstin premiered in Vienna in 1915 and was soon an international success. It appeared in Budapest as Csárdáskirályné (1916), in Moscow as u (1917), in New York as The Riviera Girl (1917) and in London as The Gipsy Princess (1921). By considering its different stagings, this article focuses on the reciprocal ways whereby Western and Eastern Europeans interact, influence, react and respond to each other. Thus the aim of the article is to bring together the different formulations of European and international theatre to show the various networks, connections and relations among the different theatre traditions both within and outside Europe; and to set up a methodology of theatre historiography which goes beyond European orientation, the East/West divide and the image of the ‘West’ as a single and unified entity.
The sound of Broadway’s mean streets: Setting New York City’s ‘edge’ in show songs
Authors: Knapp Raymond
Published: October 2013

Broadway has historically played directly to its home crowd of New Yorkers and suburbanites, providing musical stylizations that would gratify or (sometimes) challenge that audience. Thus, even for its more remote or exotic settings, Broadway has honoured audience expectations more than historical or ethnographic accuracy. But Broadway has also provided local audiences with a different kind of mirror, reflecting their native city more directly and often aiming more to disquiet than to gratify. This study considers some of these more troubling musical cityscapes across the end of the ‘golden age’ and beyond, including the comic underworld of Guys and Dolls (1950), the upbeat cynicism of Wonderful Town (1953), the playful angst of Saturday Night (1954), the incipient violence of West Side Story (1957), the sleazy underside of Gypsy (1959), the street-savvy innocence of Sweet Charity (1965), and the alienated sophistications of Company (1970) and Follies (1971). After sketching the trajectory of these diverse representations, involving five composers and an array of perspectives and moods, I focus particularly on the scores of West Side Story and Company to show how their edgy critiques inspired their composers, Leonard Bernstein and Stephen Sondheim, to explore similarly edgy musical idioms that blend familiar Broadway musical practices with an assortment of musical modernisms.
Making Broadway Musicals: An interview with Lisa Lambert
Authors: Das Joanna Dee
Published: October 2013

Lisa Lambert is an award-winning actress, comedy writer, composer and lyricist. She won a Tony Award for Best Original Score and two Drama Desk awards for Outstanding Music and Outstanding Lyrics in 2006 for her work on The Drowsy Chaperone, an original Broadway musical. Below are excerpts from a conversation among Princeton University undergraduate students, Sandy Fong (SF), Caitlin Lansing (CL) and Carly Robbins (CR), Lisa Lambert (LL), and members of a general public audience about the genesis of The Drowsy Chaperone and Lambert’s creative process. This conversation took place as part of the ‘Making Broadway Musicals: Artists and Scholars in Conversation’ symposium at Princeton University on 21 April 2012.
Reviews
Authors: Lockitt Matthew , Stith Nathan , Bonenfant Yvon
Published: October 2013

Musical Theatre, Realism And Entertainment, Millie Taylor (2012) Surrey, UK: Ashgate Publishing Limited, viii+194 pp., ISBN: 978-0-7546-6670-7, h/bk, £55.00

Loverly: The Life and Times of My Fair Lady, Dominic McHugh (2012) [Broadway Legacy Series] New York: Oxford University Press, 265 pp., ISBN: 978-0-19-982730-5, hb/k, $25.91 (US)

The Björling Sound: A Recorded Legacy, Stephen Hastings (2012) Rochester, NY: University of Rochester Press, 406 pp., ISBN: 978-1-58046-406-2, h/bk, £22.80
Inducible Presynaptic Glutamine Transport Supports Glutamatergic Transmission at the Calyx of Held Synapse
Authors: Billups Daniela , Marx Mari-Carmen , Mela Ioanna , Billups Brian
Published: October 2013

The mechanisms by which the excitatory neurotransmitter glutamate is recycled at synapses are currently unknown. By examining the functional expression of plasma membrane transporters at presynaptic terminals, we aim to elucidate some of the mechanisms of glutamate recycling. Using whole-cell voltage-clamp recordings from rat calyx of Held presynaptic terminals, our data show, for the first time, that the glutamate precursor glutamine causes the direct activation of an electrogenic, sodium-dependent presynaptic transporter, which supplies glutamine for generation of presynaptic glutamate and helps sustain synaptic transmission. Interestingly, the functional expression of this transporter at the presynaptic plasma membrane is dynamically controlled by electrical activity of the terminal, indicating that uptake of neurotransmitter precursors is controlled by the demand at an individual terminal. Induction of the transporter current is calcium-dependent and inhibited by botulinum neurotoxin C, demonstrating the involvement of SNARE-dependent exocytosis in inserting transporters into the plasma membrane when the terminal is active. Conversely, inactivity of the presynaptic terminal results in removal of transporters via clathrin-mediated endocytosis. To investigate whether the presynaptic glutamine transporter supplies the precursor for generating the synaptically released glutamate, we measured miniature EPSCs to assess vesicular glutamate content. When the presynaptic glutamate pool was turned over by synaptic activity, inhibiting the presynaptic glutamine transporters with MeAIB reduced the miniature EPSC amplitude significantly. This demonstrates that presynaptic glutamine transport is centrally involved in the production of glutamate and assists in maintaining excitatory neurotransmission.
Coding the Meaning of Sounds: Contextual Modulation of Auditory Responses in the Basolateral Amygdala
Authors: Grimsley Jasmine M. S. , Hazlett Emily G. , Wenstrup Jeffrey J.
Published: October 2013

Female mice emit a low-frequency harmonic (LFH) call in association with distinct behavioral contexts: mating and physical threat or pain. Here we report the results of acoustic, behavioral, and neurophysiological studies of the contextual analysis of these calls in CBA/CaJ mice. We first show that the acoustical features of the LFH call do not differ between contexts. We then show that male mice avoid the LFH call in the presence of a predator cue (cat fur) but are more attracted to the same exemplar of the call in the presence of a mating cue (female urine). The males thus use nonauditory cues to determine the meaning of the LFH call, but these cues do not generalize to noncommunication sounds, such as noise bursts. We then characterized neural correlates of contextual meaning of the LFH call in responses of basolateral amygdala (BLA) neurons from awake, freely moving mice. There were two major findings. First, BLA neurons typically displayed early excitation to all tested behaviorally aversive stimuli. Second, the nonauditory context modulates the BLA population response to the LFH call but not to the noncommunication sound. These results suggest that the meaning of communication calls is reflected in the spike discharge patterns of BLA neurons.
The Major Brain Cholesterol Metabolite 24(S)-Hydroxycholesterol Is a Potent Allosteric Modulator ofN-Methyl-d-Aspartate Receptors
Authors: Paul Steven M. , Doherty James J. , Robichaud Albert J. , Belfort Gabriel M. , Chow Brian Y. , Hammond Rebecca S. , Crawford Devon C. , Linsenbardt Andrew J. , Shu Hong-Jin , Izumi Yukitoshi , Mennerick Steven J. , Zorumski Charles F.
Published: October 2013

N-methyl-d-aspartate receptors (NMDARs) are glutamate-gated ion channels that are critical to the regulation of excitatory synaptic function in the CNS. NMDARs govern experience-dependent synaptic plasticity and have been implicated in the pathophysiology of various neuropsychiatric disorders including the cognitive deficits of schizophrenia and certain forms of autism. Certain neurosteroids modulate NMDARs experimentally but their low potency, poor selectivity, and very low brain concentrations make them poor candidates as endogenous ligands or therapeutic agents. Here we show that the major brain-derived cholesterol metabolite 24(S)-hydroxycholesterol (24(S)-HC) is a very potent, direct, and selective positive allosteric modulator of NMDARs with a mechanism that does not overlap that of other allosteric modulators. At submicromolar concentrations 24(S)-HC potentiates NMDAR-mediated EPSCs in rat hippocampal neurons but fails to affect AMPAR or GABAAreceptors (GABAARs)-mediated responses. Cholesterol itself and other naturally occurring oxysterols present in brain do not modulate NMDARs at concentrations ≤10 μm. In hippocampal slices, 24(S)-HC enhances the ability of subthreshold stimuli to induce long-term potentiation (LTP). 24(S)-HC also reverses hippocampal LTP deficits induced by the NMDAR channel blocker ketamine. Finally, we show that synthetic drug-like derivatives of 24(S)-HC, which potently enhance NMDAR-mediated EPSCs and LTP, restore behavioral and cognitive deficits in rodents treated with NMDAR channel blockers. Thus, 24(S)-HC may function as an endogenous modulator of NMDARs acting at a novel oxysterol modulatory site that also represents a target for therapeutic drug development.
Top-Down Control of Visual Responses to Fear by the Amygdala
Authors: Furl Nicholas , Henson Richard N. , Friston Karl J. , Calder Andrew J.
Published: October 2013

The visual cortex is sensitive to emotional stimuli. This sensitivity is typically assumed to arise when amygdala modulates visual cortex via backwards connections. Using human fMRI, we compared dynamic causal connectivity models of sensitivity with fearful faces. This model comparison tested whether amygdala modulates distinct cortical areas, depending on dynamic or static face presentation. The ventral temporal fusiform face area showed sensitivity to fearful expressions in static faces. However, for dynamic faces, we found fear sensitivity in dorsal motion-sensitive areas within hMT+/V5 and superior temporal sulcus. The model with the greatest evidence included connections modulated by dynamic and static fear from amygdala to dorsal and ventral temporal areas, respectively. According to this functional architecture, amygdala could enhance encoding of fearful expression movements from video and the form of fearful expressions from static images. The amygdala may therefore optimize visual encoding of socially charged and salient information.
Boosting Regulatory T Cells Limits Neuroinflammation in Permanent Cortical Stroke
Authors: Liesz Arthur , Zhou Wei , Na Shin-Young , Hämmerling Günter J. , Garbi Natalio , Karcher Simone , Mracsko Eva , Backs Johannes , Rivest Serge , Veltkamp Roland
Published: October 2013

Inflammatory mechanisms contribute substantially to secondary tissue injury after brain ischemia. Regulatory T cells (Tregs) are key endogenous modulators of postischemic neuroinflammation. We investigated the potential of histone deacetylase inhibition (HDACi) to enhance Treg potency for experimental stroke in mice. HDACi using trichostatin A increased the number of Tregs and boosted their immunosuppressive capacity and interleukin (IL)-10 expression.In vivotreatment reduced infarct volumes and behavioral deficits after cortical brain ischemia, attenuated cerebral proinflammatory cytokine expression, and increased numbers of brain-invading Tregs. A similar effect was obtained using tubastatin, a specific inhibitor of HDAC6 and a key HDAC in Foxp3 regulation. The neuroprotective effect of HDACi depended on the presence of Foxp3+Tregs, andin vivoandin vitrostudies showed that the anti-inflammatory cytokine IL-10 was their main mediator. In summary, modulation of Treg function by HDACi is a novel and potent target to intervene at the center of neuroinflammation. Furthermore, this novel concept of modulating endogenous immune mechanisms might be translated to a broad spectrum of diseases, including primary neuroinflammatory and neurodegenerative disorders.