bluuebunny/crossref_metadata_2025 huggingface dataset:
Centrifugal effects on the dynamic characteristics of high speed hydrostatic thrust bearing lubricated by low viscosity fluid
Authors: Wang Lei , Jiang Shuyun
Published: May 2014

The effect of the centrifugal force of the fluid film on the performance of the high speed hydrostatic thrust bearing lubricated by low viscosity fluid cannot be neglected. Considering the centrifugal inertia effect, concentrated inertia effect at the recess edge, and the misalignment effect, the thermo-hydrodynamic lubrication model is established by using the reduced Navier–Stokes equation, the energy equation, and the bulk flow theory. The effects of centrifugal forces on dynamic performances of the high speed thrust bearing with different supply pressures and rotational speeds have been analyzed systematically. The results show that the centrifugal force reduces the axial and angular stiffness and hardly affects the damping coefficients; the centrifugal effects decrease with the increasing of eccentricity ratio and misalignment angle.
Young Norwegian-Pakistani women and sport
Authors: Walseth Kristin , Strandbu Åse
Published: May 2014

Studies from several countries show that girls with an immigrant background participate in organized sports to a lesser extent than other young people. Barriers related to culture and religion serve in many of these studies as explanations. In this article we suggest that the notions of culture and religion in this field of studies could be elaborated and we distinguish between three different approaches: (a) culture and religiosity as restricting factors; (b) culture and religiosity as embodied dispositions for action; and lastly (c) culture and religiosity as the basis for reflexive praxis. Analyses of qualitative interviews with young Norwegian-Pakistani women show the relevance of the three perspectives. The study’s most important contribution is to illustrate how culture and religiosity have multiple meanings. The three perspectives presented in this paper might be used as analytical tools in future research on minority women and sports.
Use of fractional flow reserve in the assessment of chronic mesenteric ischemia
Authors: Sadiq Immad , Chamakura Sanjayant , Siddiqi Saadi , Margey Ronan , Azemi Talhat
Published: May 2014

Chronic mesenteric ischemia (CMI) is a rare condition that is usually the result of atherosclerotic obstructive disease affecting the mesenteric arteries. The classic triad of post-prandial pain, food aversion and weight loss is not always present, often leading to low clinical suspicion for CMI and underdiagnosis. Non-invasive evaluation for CMI usually starts with mesenteric arterial duplex scanning, followed by computed tomography angiography, magnetic resonance angiography or conventional angiography, the latter being the gold standard for establishing its diagnosis. However, angiography alone has been demonstrated in coronary and other vascular beds to be inaccurate in predicting the physiologic and hemodynamic significance of a certain subset of atherosclerotic stenoses. We present the case of a patient with risk factors and symptoms suggestive of CMI who underwent angiography. However, angiography was equivocal and invasive physiologic testing was required to confirm the diagnosis and guide revascularization.
ICAM-1 and SRD5A1 gene polymorphisms in symptomatic peripheral artery disease
Authors: Barresi Vincenza , Signorelli Salvatore S , Musso Nicolò , Anzaldi Massimiliano , Fiore Valerio , Alberghina Mario , Condorelli Daniele Filippo
Published: May 2014

The genotype distribution of two gene polymorphisms, previously associated with peripheral artery disease (PAD), has been evaluated in a population of diabetic (DPAD) and non-diabetic (NDPAD) patients affected by symptomatic PAD (stages II–IV). A decreased frequency of the AA genotype of rs5498 (ICAM-1) was observed in the PAD subjects compared to controls but this result did not reach statistical significance ( p=0.06 by chi-squared test). On the contrary, a significant increase in the frequency of the GG homozygous genotype of rs248793 (SRD5A1) was observed in the PAD patient group in comparison to controls ( p=0.01). These data confirm that the GG genotype of rs248793 in the SRD5A1 gene is significantly associated with symptomatic PAD and show a trend towards a stronger association with the non-diabetic status.
Controversies regarding the new oral anticoagulants for stroke prevention in patients with atrial fibrillation
Authors: Mohanty Bibhu D , Looser Patrick M , Gokanapudy Lakshmi R , Handa Rishi , Mohanty Sudipta , Choi Sharon S , Goldman Martin E , Fuster Valentin , Halperin Jonathan L
Published: May 2014

Increasing use of the new oral anticoagulants (NOACs) – dabigatran, rivaroxaban, and apixaban – has prompted considerable discussion in the medical community even as warfarin remains the mainstay of therapy. This article raises 10 controversial issues regarding the use of NOACs for stroke prevention in patients with atrial fibrillation, and offers a review of the latest available evidence. We provide a brief overview of the mechanism and dosing of these drugs, as well as a summary of the key clinical trials that have brought them into the spotlight. Comparative considerations relative to warfarin such as NOAC safety, efficacy, bleeding risk, reversibility, drug-transitioning and use in patients well controlled on warfarin are addressed. Use in select populations such as the elderly, those with coronary disease, renal impairment, or on multiple anti-platelet drugs is also discussed. Finally, we consider such specific issues as comparative efficacy, off-label use, cost, rebound and management during events. Ultimately, the rise of the NOACs to mainstream use will depend on further data and clinical experience amongst the medical community.
The role of novel anticoagulants in the management of venous thromboembolism
Authors: Skeik Nedaa , Murphy Caleb J , Porten Brandon R
Published: May 2014

Venous thromboembolism (VTE) is a common health condition with a high mortality and morbidity as well as significant health cost. Traditional treatment with parenteral heparin followed by vitamin K antagonist (VKA) has helped to decrease both morbidity and mortality over years. However, difficulties with warfarin such as INR monitoring, drug-drug interactions, and dietary restrictions has led to research for new anticoagulants. Thus, novel anticoagulants such as direct thrombin and factor X inhibitors have been developed and studied for various indications including the management of VTE. There is now good evidence that some novel anticoagulants are at least as effective as traditional anticoagulation therapy with probably safer outcomes. We have reviewed the literature on the medical management of VTE with the focus on the role of dabigatran, rivaroxaban, apixaban and edoxaban for this indication.
Using Virtual Reality to Explore Self-Regulation in High-Risk Settings
Authors: Kniffin Tracey C. , Carlson Charles R. , Ellzey Antonio , Eisenlohr-Moul Tory , Beck Kelly Battle , McDonald Renee , Jouriles Ernest N.
Published: May 2014

Virtual reality (VR) models allow investigators to explore high-risk situations carefully in the laboratory using physiological assessment strategies and controlled conditions not available in field settings. This article introduces the use of a virtual experience to examine the influence of self-regulatory skills training on female participants’ reactions to a high-risk encounter with an aggressive male. Sixty-three female participants were recruited for the study. Demographic data indicated that 54% of the participants were not currently in a relationship, 36.5% were in a committed relationship, and 9.5% were occasionally dating. After obtaining informed consent, participants were assigned randomly to either a diaphragmatic breathing training condition or an attention control condition. Results indicated that both groups rated the virtual environment as equally realistic; the aggressive advances of the male were also perceived as equally real across the two experimental groups. Physiological data indicated that there were no differences between the groups on respiration or cardiovascular measures during baseline or during the VR task. After the VR experience, however, the participants in the breathing training condition had lower respiration rates and higher heart rate variability measures than those in the control condition. The results suggest that VR platforms provide a realistic and challenging environment to examine how self-regulation procedures may influence behavioral outcomes. Real-time dynamic engagement in a virtual setting affords investigators with an opportunity to evaluate the utility of self-regulatory skills training for improving safety in situations where there are uncertain and risky outcomes.
A nurse-run clinic for patients with incidentally discovered small abdominal aortic aneurysms is feasible and cost-effective
Authors: Griffin JL , Clarke GA , Roake JA , Lewis DR
Published: May 2014

Introduction

Patients with incidentally discovered small abdominal aortic aneurysms (AAA) require assessment by a vascular surgery department for possible enrollment in a surveillance programme. Our unit implemented a vascular nurse-run AAA clinic in October 2010. The aim of this study was to assess the feasibility of a specialist nurse-run small AAA clinic.

Methods

Demographic and clinical data were collected prospectively for all patients seen in the new vascular nurse clinic between October 2010 and November 2012. A validated AAA operative mortality score was used to aid decision making by the vascular nurse.

Results

Some 250 patients were seen in the clinic. 198 (79.2%) patients were enrolled in surveillance, 40 (16%) declined enrollment and 12 (4.8%) were referred to a consultant clinic for further assessment. The majority of patients were male and the mean age was 73.7 years. Co-morbidities included hypertension, a history of cardiovascular disease, and hyperlipidaemia. The majority of referrals were considered to be low operative risk. No aneurysms ruptured whilst under surveillance.

Conclusions

A nurse-run clinic that assesses patients with incidentally discovered small AAAs for inclusion in AAA surveillance is a feasible alternative to assessment of these patients in a consultant-run clinic.
Carotid endarterectomy under local and/or regional anesthesia has less risk of myocardial infarction compared to general anesthesia: An analysis of national surgical quality improvement program database
Authors: Kfoury Elias , Dort Jonathan , Trickey Amber , Crosby Moira , Donovan Jean , Hashemi Homayoun , Mukherjee Dipankar
Published: May 2014

Multiple studies have evaluated the effect of anesthesia type on carotid endarterectomy with inconsistent results. Our study compared 30-day postoperative myocardial infarction, stroke, and mortality between carotid endarterectomy under local or regional anesthesia and carotid endarterectomy under general anesthesia utilizing National Surgical Quality Improvement Program database. All patients listed in National Surgical Quality Improvement Program database that underwent carotid endarterectomy under general anesthesia and local or regional anesthesia from 2005 to 2011 were included with the exception of patients undergoing simultaneous carotid endarterectomy and coronary artery bypass grafting. The data revealed substantial differences between the two groups compared, and these were adjusted using multiple logistic regression. Postoperative myocardial infarction, stroke, and death at 30 days were compared between the two groups. A total of 42,265 carotid endarterectomy cases were included. A total of 37,502 (88.7%) were performed under general anesthesia and 4763 (11.3%) under local or regional anesthesia. Carotid endarterectomy under local or regional anesthesia had a significantly decreased risk of 30-day postoperative myocardial infarction when compared to carotid endarterectomy under general anesthesia (0.4% vs 0.86%, p = 0.012). No statistically significant differences were found in postoperative stroke or mortality. Carotid endarterectomy under local or regional anesthesia carries a decreased risk of postoperative myocardial infarction when compared to carotid endarterectomy under general anesthesia. Therefore, patients at risk of postoperative myocardial infarction undergoing carotid endarterectomy, consideration of local or regional anesthesia may reduce that risk.
Glycemic Variability in Nondiabetic Morbidly Obese Persons
Authors: Salkind Sara J. , Huizenga Robert , Fonda Stephanie J. , Walker M. Susan , Vigersky Robert A.
Published: May 2014

Background:

Glycemic variability (GV) is correlated with oxidative stress which may lead to increased cardiovascular risk and poor clinical outcomes in people with prediabetes and diabetes. We sought to understand whether morbidly obese persons without diabetes by standard criteria have dysglycemia as measured by GV.

Methods:

We performed an observational study of GV metrics and carotid intima media thickness (CIMT) in 21 morbidly obese normoglycemic and 15 morbidly obese prediabetic applicants to The Biggest Loser television show. The results were compared to previously published studies in normoglycemic nonobese and obese individuals. Glucose was measured with a masked continuous glucose monitor (CGM) over 3 to 8 days and carotid intima media thickness (CIMT) was determined by ultrasound. CGM-derived GV metrics for GV were coefficient of variation (CV), standard deviation (SD), mean amplitude of glycemic excursions (MAGE), continuous overall net glycemic action–1 hour (CONGA1), and mean of daily differences (MODD).

Results:

We found that morbidly obese subjects (n = 21) who were normoglycemic by standard criteria had higher GV (CV = 22%, SD = 24.2 mg/dl and MAGE = 48.6 mg/dl) than previous reports of normoglycemic, nonobese individuals (CV = 12-18%, SD = 11.5-15.0 mg/dl, and MAGE = 26.3-28.3 mg/dl). Morbidly obese prediabetic subjects (n = 15) had GV metrics indistinguishable from those morbidly obese subjects who were normoglycemic. CIMT was higher in both morbidly obese groups compared with historical age- and sex-matched controls.

Conclusions:

Normoglycemic and prediabetic morbidly obese individuals have higher GV compared with normal weight, nondiabetic individuals. We speculate that this may increase the risk for macrovascular disease through excessive oxidative stress.
A Hero or Sissy? Exploring Media Framing of NFL Quarterbacks Injury Decisions
Authors: Sanderson Jimmy , Weathers Melinda , Grevious Alexia , Tehan Maggie , Warren Samantha
Published: May 2014

There has been growing attention on health and safety issues in sport, most notably football. Consequently, it is important that communication scholars attend to this topic. This research explored print media framing in response to two injury situations involving National Football League quarterbacks—Jay Cutler and Robert Griffin III. An analysis of 177 newspaper articles revealed 11 frames that were used to discuss these injuries. The most prominent frame for Cutler was support while shifting the blame was most prominent for Griffin. The results suggest that sports journalists framing of injuries could potentially be a catalyst to shift football cultural norms towards valuing players who put their health first. The results also reveal that organizations may shoulder most of the blame for players’ injuries, which suggests a short-term setback may be more beneficial in the long-term interest of the organization.
Characterisation of thermal cycling induced cavitation in particle reinforced metal matrix composites by three-dimensional (3D) X-ray synchrotron tomography
Authors: Chapman N. C. , Silva J. , Williams J. J. , Chawla N. , Xiao X.
Published: May 2014

Metal matrix composites are known for their high strength, fatigue resistance, and wear resistance. The coefficient of thermal expansion between the reinforcement and matrix can result in thermal stresses during thermal cycling. In this paper we quantify the evolution of cavitation damage in SiC particle reinforced aluminium alloy matrix composite subjected to thermal cycling by X-ray synchrotron tomography at the advanced photon source at the Argonne National Laboratory. It will be shown that, while surface examination did not show significant damage, X-ray synchrotron tomography enabled us to resolve and quantify the amount and nature of cavitation with increasing thermal cycling. The influence of the microstructure in damage initiation and evolution is discussed.
Treatment of acute pancreatitis with protease inhibitors administered through intravenous infusion: an updated systematic review and meta-analysis
Authors: Seta Takeshi , Noguchi Yoshinori , Shikata Satoru , Nakayama Takeo
Published: May 2014

Background

The intravenous use of protease inhibitors in patients with acute pancreatitis is still controversial. The purpose of this study was to evaluate the effectiveness of protease inhibitors intravenously administered to prevent pancreatitis-associated complications.

Methods

We updated our previous meta-analysis with articles of randomized controlled trials published from January 1965 to March 2013 on the effectiveness of protease inhibitors for acute pancreatitis. A systematic search of PubMed, EMBASE, the Cochrane Library, and Japana Centra Revuo Medicina was conducted. In addition, Internet-based registries (ClinicalTrials.gov, controlled-trials.com, UMIN, JMACCT, and JAPIC) were used to search for on-going clinical trials. Furthermore, references of review articles and previously published meta-analyses were handsearched. The main outcome of interest was the overall mortality rate from acute pancreatitis.

Results

Seventeen trials were selected for analysis. Overall, protease inhibitors did not achieve a significant risk reduction in mortality (pooled risk difference [RD], -0.02; 95% Confidence Interval [CI], -0.05 to 0.01; number needed to treat [NNT], 74.8) with low heterogeneity. A subgroup analysis in moderate to severe pancreatitis (defined by control mortality rate [CMR] >0.10) did not show a significant effect of protease inhibitors to prevent death (pooled RD, -0.03; 95% CI, -0.07 to 0.01; NNT, 1603.9) with low heterogeneity. An additional subgroup analysis of two trials with CMR >0.20 (i.e., low quality) revealed a significant risk reduction.

Conclusion

The present meta-analysis re-confirmed that there is no solid evidence that supports the intravenous use of protease inhibitors to prevent death due to acute pancreatitis.
Examination of historical paintings by state-of-the-art hyperspectral imaging methods: from scanning infra-red spectroscopy to computed X-ray laminography
Authors: Legrand Stijn , Vanmeert Frederik , Van der Snickt Geert , Alfeld Matthias , De Nolf Wout , Dik Joris , Janssens Koen
Published: May 2014

The development of advanced methods for non-destructive selective imaging of painted works of art at the macroscopic level based on radiation in the X-ray and infrared range of the electromagnetic spectrum are concisely reviewed. Such methods allow to either record depth-selective, element-selective or species-selective images of entire paintings. Camera-based ‘full field’ methods (that record the image data in parallel) can be discerned next to scanning methods (that build up distributions in a sequential manner by scanning a beam of radiation over the surface of an artefact). Six methods are discussed: on the one hand, macroscopic X-ray fluorescence and X-ray diffraction imaging and X-ray laminography and on the other hand macroscopic Mid and Near Infrared hyper- and full spectral imaging and Optical Coherence Tomography. These methods can be considered to be improved versions of the well-established imaging methods employed worldwide for examination of paintings, i.e., X-ray radiography and Infrared reflectography. Possibilities and limitations of these new imaging techniques are outlined.
PEG-ing down (and preventing?) the cause of pegloticase failure
Authors: Abeles Aryeh M
Published: May 2014

Pegloticase is a powerful but underutilized weapon in the rheumatologist’s armamentarium. The drug’s immunogenicity leads to neutralizing antibody formation and rapid loss of efficacy in roughly one-half of all patients, which remains an impediment to broader use. New data, however, suggest that drug survival might improve with concomitant immunosuppressive agent (s), which merits further study. Efficacy appears to be unchanged when pegloticase is infused at 3-week (rather than 2-week) intervals. Stretching the time between infusions may also improve patient adherence and allow for earlier identification of transient responders.
JMJD2A contributes to breast cancer progression through transcriptional repression of the tumor suppressor ARHI
Authors: Li Li-Liang , Xue Ai-Min , Li Bei-Xu , Shen Yi-Wen , Li Yu-Hua , Luo Cheng-Liang , Zhang Ming-Chang , Jiang Jie-Qing , Xu Zu-De , Xie Jian-Hui , Zhao Zi-Qin
Published: May 2014

Introduction

Breast cancer is a worldwide health problem and the leading cause of cancer death among females. We previously identified Jumonji domain containing 2A (JMJD2A) as a critical mediator of breast cancer proliferation, migration and invasion. We now report that JMJD2A could promote breast cancer progression through transcriptional repression of the tumor suppressor aplasia Ras homolog member I (ARHI).

Methods

Immunohistochemistry was performed to examine protein expressions in 155 cases of breast cancer and 30 non-neoplastic tissues. Spearman correlation analysis was used to analyze the correlation between JMJD2A expression and clinical parameters as well as several tumor regulators in 155 cases of breast cancer. Gene and protein expressions were monitored by quantitative polymerase chain reaction (qPCR) and Western blot. Results from knockdown of JMJD2A, overexpression of JMJD2A, Co-immunoprecipitation (Co-IP) assay, dual luciferase reporter gene assay and chromatin immunoprecipitation (ChIP) elucidated molecular mechanisms of JMJD2A action in breast cancer progression. Furthermore, the effects of ARHI overexpression on JMJD2A-mediated tumor progression were investigated in vitro and in vivo. For in vitro experiments, cell proliferation, wound-healing, migration and invasion were monitored by cell counting, scratch and Boyden Chamber assays. For in vivo experiments, control cells and cells stably expressing JMJD2A alone or together with ARHI were inoculated into mammary fat pads of mice. Tumor volume, tumor weight and metastatic nodules were measured by caliper, electronic balance and nodule counting, respectively.

Results

JMJD2A was highly expressed in human breast cancers and positively correlated with tumor progression. Knockdown of JMJD2A increased ARHI expression whereas overexpression of JMJD2A decreased ARHI expression at both protein and mRNA levels. Furthermore, E2Fs and histone deacetylases were involved in the transcriptional repression of ARHI expression by JMJD2A. And the aggressive behavior of JMJD2A in breast cancers could be reversed by re-expression of ARHI in vitro and in vivo.

Conclusion

We demonstrated a cancer-promoting effect of JMJD2A and defined a novel molecular pathway contributing to JMJD2A-mediated breast cancer progression.
SoxNeuro orchestrates central nervous system specification and differentiation in Drosophila and is only partially redundant with Dichaete
Authors: Ferrero Enrico , Fischer Bettina , Russell Steven
Published: May 2014

Background

Sox proteins encompass an evolutionarily conserved family of transcription factors with critical roles in animal development and stem cell biology. In common with vertebrates, the Drosophila group B proteins SoxNeuro and Dichaete are involved in central nervous system development, where they play both similar and unique roles in gene regulation. Sox genes show extensive functional redundancy across metazoans, but the molecular basis underpinning functional compensation mechanisms at the genomic level are currently unknown.

Results

Using a combination of genome-wide binding analysis and gene expression profiling, we show that SoxNeuro directs embryonic neural development from the early specification of neuroblasts through to the terminal differentiation of neurons and glia. To address the issue of functional redundancy and compensation at a genomic level, we compare SoxNeuro and Dichaete binding, identifying common and independent binding events in wild-type conditions, as well as instances of compensation and loss of binding in mutant backgrounds.

Conclusions

We find that early aspects of group B Sox functions in the central nervous system, such as stem cell maintenance and dorsoventral patterning, are highly conserved. However, in contrast to vertebrates, we find that Drosophila group B1 proteins also play prominent roles during later aspects of neural morphogenesis. Our analysis of the functional relationship between SoxNeuro and Dichaete uncovers evidence for redundant and independent functions for each protein, along with unexpected examples of compensation and interdependency, thus providing new insights into the general issue of transcription factor functional redundancy.
Lentiviral and targeted cellular barcoding reveals ongoing clonal dynamics of cell lines in vitro and in vivo
Authors: Porter Shaina N , Baker Lee C , Mittelman David , Porteus Matthew H
Published: May 2014

Background

Cell lines are often regarded as clonal, even though this simplifies what is known about mutagenesis, transformation and other processes that destabilize them over time. Monitoring these clonal dynamics is important for multiple areas of biomedical research, including stem cell and cancer biology. Tracking the contributions of individual cells to large populations, however, has been constrained by limitations in sensitivity and complexity.

Results

We utilize cellular barcoding methods to simultaneously track the clonal contributions of tens of thousands of cells. We demonstrate that even with optimal culturing conditions, common cell lines including HeLa, K562 and HEK-293 T exhibit ongoing clonal dynamics. Starting a population with a single clone diminishes but does not eradicate this phenomenon. Next, we compare lentiviral and zinc-finger nuclease barcode insertion approaches, finding that the zinc-finger nuclease protocol surprisingly results in reduced clonal diversity. We also document the expected reduction in clonal complexity when cells are challenged with genotoxic stress. Finally, we demonstrate that xenografts maintain clonal diversity to a greater extent than in vitro culturing of the human non-small-cell lung cancer cell line HCC827.

Conclusions

We demonstrate the feasibility of tracking and quantifying the clonal dynamics of entire cell populations within multiple cultured cell lines. Our results suggest that cell heterogeneity should be considered in the design and interpretation of in vitro culture experiments. Aside from clonal cell lines, we propose that cellular barcoding could prove valuable in modeling the clonal behavior of heterogeneous cell populations over time, including tumor populations treated with chemotherapeutic agents.
The Medial Amygdala-Medullary PrRP-Synthesizing Neuron Pathway Mediates Neuroendocrine Responses to Contextual Conditioned Fear in Male Rodents
Authors: Yoshida Masahide , Takayanagi Yuki , Onaka Tatsushi
Published: May 2014

Fear responses play evolutionarily beneficial roles, although excessive fear memory can induce inappropriate fear expression observed in posttraumatic stress disorder, panic disorder, and phobia. To understand the neural machineries that underlie these disorders, it is important to clarify the neural pathways of fear responses. Contextual conditioned fear induces freezing behavior and neuroendocrine responses. Considerable evidence indicates that the central amygdala plays an essential role in expression of freezing behavior after contextual conditioned fear. On the other hand, mechanisms of neuroendocrine responses remain to be clarified. The medial amygdala (MeA), which is activated after contextual conditioned fear, was lesioned bilaterally by infusion of N-methyl-d-aspartate after training of fear conditioning. Plasma oxytocin, ACTH, and prolactin concentrations were significantly increased after contextual conditioned fear in sham-lesioned rats. In MeA-lesioned rats, these neuroendocrine responses but not freezing behavior were significantly impaired compared with those in sham-lesioned rats. In contrast, the magnitudes of neuroendocrine responses after exposure to novel environmental stimuli were not significantly different in MeA-lesioned rats and sham-lesioned rats. Contextual conditioned fear activated prolactin-releasing peptide (PrRP)-synthesizing neurons in the medulla oblongata. In MeA-lesioned rats, the percentage of PrRP-synthesizing neurons activated after contextual conditioned fear was significantly decreased. Furthermore, neuroendocrine responses after contextual conditioned fear disappeared in PrRP-deficient mice. Our findings suggest that the MeA-medullary PrRP-synthesizing neuron pathway plays an important role in neuroendocrine responses to contextual conditioned fear.
Implantation Failure in Female Kiss1−/− Mice Is Independent of Their Hypogonadic State and Can Be Partially Rescued by Leukemia Inhibitory Factor
Authors: Calder Michele , Chan Yee-Ming , Raj Renju , Pampillo Macarena , Elbert Adrienne , Noonan Michelle , Gillio-Meina Carolina , Caligioni Claudia , Bérubé Nathalie G. , Bhattacharya Moshmi , Watson Andrew J. , Seminara Stephanie B. , Babwah Andy V.
Published: May 2014

The hypothalamic kisspeptin signaling system is a major positive regulator of the reproductive neuroendocrine axis, and loss of Kiss1 in the mouse results in infertility, a condition generally attributed to its hypogonadotropic hypogonadism. We demonstrate that in Kiss1−/− female mice, acute replacement of gonadotropins and estradiol restores ovulation, mating, and fertilization; however, these mice are still unable to achieve pregnancy because embryos fail to implant. Progesterone treatment did not overcome this defect. Kiss1+/− embryos transferred to a wild-type female mouse can successfully implant, demonstrating the defect is due to maternal factors. Kisspeptin and its receptor are expressed in the mouse uterus, and we suggest that it is the absence of uterine kisspeptin signaling that underlies the implantation failure. This absence, however, does not prevent the closure of the uterine implantation chamber, proper alignment of the embryo, and the ability of the uterus to undergo decidualization. Instead, the loss of Kiss1 expression specifically disrupts embryo attachment to the uterus. We observed that on the day of implantation, leukemia inhibitory factor (Lif), a cytokine that is absolutely required for implantation in mice, is weakly expressed in Kiss1−/− uterine glands and that the administration of exogenous Lif to hormone-primed Kiss1−/− female mice is sufficient to partially rescue implantation. Taken together, our study reveals that uterine kisspeptin signaling regulates glandular Lif levels, thereby identifying a novel and critical role for kisspeptin in regulating embryo implantation in the mouse. This study provides compelling reasons to explore this role in other species, particularly livestock and humans.
SIRT3 Positively Regulates the Expression of Folliculogenesis- and Luteinization-Related Genes and Progesterone Secretion by Manipulating Oxidative Stress in Human Luteinized Granulosa Cells
Authors: Fu Houju , Wada-Hiraike Osamu , Hirano Mana , Kawamura Yumiko , Sakurabashi Ayako , Shirane Akira , Morita Yoshihiro , Isono Wataru , Oishi Hajime , Koga Kaori , Oda Katsutoshi , Kawana Kei , Yano Tetsu , Kurihara Hiroki , Osuga Yutaka , Fujii Tomoyuki
Published: May 2014

SIRT3 is a member of the sirtuin family and has recently emerged as a vital molecule in controlling the generation of reactive oxygen species (ROS) in oocytes. Appropriate levels of ROS play pivotal roles in human reproductive medicine. The aim of the present study was to investigate SIRT3 expression and analyze the SIRT3-mediated oxidative response in human luteinized granulosa cells (GCs). Human ovarian tissues were subjected to immunohistochemical analysis to localize SIRT3 expression. Hydrogen peroxide and human chorionic gonadotropin were used to analyze the relationship between ROS and SIRT3 by quantitative RT-PCR and Western blotting. Intracellular levels of ROS were investigated by fluorescence after small interfering RNA–mediated knockdown of SIRT3 in human GCs. To uncover the role of SIRT3 in folliculogenesis and luteinization, mRNA levels of related genes and the progesterone concentration were analyzed by quantitative RT-PCR and immunoassays, respectively. We detected the expression of SIRT3 in the GCs of the human ovary. The mRNA levels of SIRT3, catalase, and superoxide dismutase 1 were up-regulated by hydrogen peroxide in both COV434 cells and human GCs and down-regulated by human chorionic gonadotropin. Knockdown of SIRT3 markedly elevated ROS generation in human GCs. In addition, SIRT3 depletion resulted in decreased mRNA expression of aromatase, 17β-hydroxysteroid dehydrogenase 1, steroidogenic acute regulatory protein, cholesterol side-chain cleavage enzyme, and 3β-hydroxysteroid dehydrogenase in GCs and thus resulted in decreased progesterone secretion. These results have the important clinical implication that SIRT3 might play a positive role in the folliculogenesis and luteinization processes in GCs, possibly by sensing and regulating the generation of ROS. Activation of SIRT3 function might help to sustain human reproduction by maintaining GCs as well as oocytes.
Leptin Induces Hippocampal Synaptogenesis via CREB-Regulated MicroRNA-132 Suppression of p250GAP
Authors: Dhar Matasha , Zhu Mingyan , Impey Soren , Lambert Talley J. , Bland Tyler , Karatsoreos Ilia N. , Nakazawa Takanobu , Appleyard Suzanne M. , Wayman Gary A.
Published: May 2014

Leptin acts in the hippocampus to enhance cognition and reduce depression and anxiety. Cognitive and emotional disorders are associated with abnormal hippocampal dendritic spine formation and synaptogenesis. Although leptin has been shown to induce synaptogenesis in the hypothalamus, its effects on hippocampal synaptogenesis and the mechanism(s) involved are not well understood. Here we show that leptin receptors (LepRs) are critical for hippocampal dendritic spine formation in vivo because db/db mice lacking the long form of the leptin receptor (LepRb) have reduced spine density on CA1 and CA3 neurons. Leptin promotes the formation of mature spines and functional glutamate synapses on hippocampal pyramidal neurons in both dissociated and slice cultures. These effects are blocked by short hairpin RNAs specifically targeting the LepRb and are absent in cultures from db/db mice. Activation of the LepR leads to cAMP response element–binding protein (CREB) phosphorylation and initiation of CREB-dependent transcription via the MAPK kinase/Erk pathway. Furthermore, both Mek/Erk and CREB activation are required for leptin-induced synaptogenesis. Leptin also increases expression of microRNA-132 (miR132), a well-known CREB target, which is also required for leptin-induced synaptogenesis. Last, leptin suppresses the expression of p250GAP, a miR132 target, and this suppression is obligatory for leptin's effects as is the downstream target of p250GAP, Rac1. LepRs appear to be critical in vivo as db/db mice have lowered hippocampal miR132 levels and elevated p250GAP expression. In conclusion, we identify a novel signaling pathway by which leptin increases synaptogenesis through inducing CREB transcription and increasing microRNA-mediated suppression of p250GAP activity, thus removing a known inhibitor of Rac1-stimulated synaptogenesis.
Othello's Pathologies: Reading Adolfo Caminha with Lombroso
Authors: Braga-Pinto César
Published: May 2014

Given the growing concern with urban crime and the fate of the black man in the aftermath of the abolition of slavery in Brazil in 1888, it is not surprising that the figure of Othello in its various versions, appropriations, and adaptations would become emblematic. In this essay I read the Brazilian novel Bom-Crioulo, written by Adolfo Caminha in 1895, in light of Cesare Lombroso's criminal anthropology. I argue that to read this novel — which deals with crime, race, sexual perversion, and jealousy — in the context of fin-de-siècle criminology and what I call “Othello's pathologies,” rather than to celebrate its explicit and supposedly benevolent (or ambivalent) approach to homosexuality, is not just to be faithful to the literary work and its historical context. More importantly, I contend that the novel may help us examine how stereotypes are reproduced, as well as the assumptions regarding the immutability of race and sexuality.
The Problem of Look-Alike Characters in theVulgate Cycle of the Arthurian Romancesand Juan Manuel'sEl Conde Lucanor
Authors: de Looze Laurence
Published: May 2014

Medieval people knew as well as we do that no two people could look exactly alike. But the question of look-alikes was nevertheless a fascinating one because it opened up a potential gap between external manifestation and deeper identity. What did it mean for the ontology of the self if one person could be substituted for another with nobody being the wiser? This article examines two medieval reflections on the possibility of an absolute resemblance that enables one character to be substituted for another. The first is the case of the “False Guenevere” in the Lancelot section of the enormous thirteenth-century Vulgate Cycle of the Arthurian romances, and the second is from Spain: El Conde Lucanor by the great fourteenth-century writer Don Juan Manuel. The two instances contrast nicely. In the first, Queen Guenevere's look-alike half-sister arrives at Arthur's court with the false claim that she is the true Guenevere and that the sitting queen has usurped her place. Indeed, she triumphs temporarily until Lancelot restores the proper order through trial by combat. In the second, an angel counterfeits a king's physiognomy (after the king commits blasphemy) and dresses in his clothes, leaving him only a pauper's vestments. In the Arthurian tale, the problem posed is how to know the true inner self when two identical-looking women both claim to be the “true” queen — a question that is complicated by the fact that the “true” Guenevere has been “false” for many years due to her adulterous affair with Lancelot. Conversely, Juan Manuel poses the question of identity as one of context: when the king is deprived of the trappings of his kingship, no one recognizes him. Both texts point up the problems of signification and identity that haunted medieval thinking. What is the relationship between one's outer appearance and inner nature? What is the relationship between a sign and what it signifies?
Between Mourning and Melancholy: Narrative Ethics in Fyodor Dostoevsky and Witold Gombrowicz
Authors: Spektor Alex
Published: May 2014

The essay offers a comparative study of “narrative ethics” in the prose of Fyodor Dostoevsky and Witold Gombrowicz. Analyzing the relationship between the texts' poetics and moral philosophy, the essay investigates how narrative dynamics of fiction shape the ethical parameters for the reader's engagement with the text. The argument aligns the differences in each author's narrative ethics with the differences between modernist and postmodernist modes of addressing the loss of ontological certainty as outlined by Brian McHale in Postmodernist Fiction. Thus, this comparison strives to trace the evolution of late nineteenth- and twentieth-century literature — from the ontologic instability of modernist prose to the ontologic plurality of postmodernist prose — with the focus on how this shift affects the formation of the subjectivity of the reader. The author proposes that Freud's conceptualization of melancholy and mourning as two processes describing the subject's dealing with loss can be a productive theoretical framework for understanding how modernist and postmodernist fiction in general (and that of Dostoevsky and Gombrowicz in particular) deals with the loss of ontological certainty. The essay argues that this psychoanalytic conceptual framework — elaborated further by an analysis of political and philosophical takes on it by Judith Butler and Julia Kristeva —allows us to see the shift between modernist and postmodernist fiction in intersubjective terms, thus situating it within the ethical discursive sphere.
Risk and Utopia
Authors: Morris Paul , Paasonen Susanna
Published: May 2014

The utopian promise of porn is one of carnal intensity, sexual abundance, and pleasure. Building on Richard Dyer's discussion of the utopian aspects of entertainment, this article expands his conceptualization to contemporary pornography and the gay bareback subculture in particular. Structured as a dialogue between a gay bareback porn producer and a media studies scholar, it explores the sexual politics of barebacking, the notion of risk in gay sex, the mediation of intensity and sensation within pornography, the role of online porn distribution, and the uses of music in porn. These strands of dialogue are tied to a conceptualization of utopian sensibility within bareback pornography as an issue of transparency, community, abundance, energy, and intensity. The authors argue for the centrality of fleshiness and viscerality in pornography as well as the necessity to account for such carnal intensity, or resonance, in studies of the genre.
Looking for Jiro Onuma
Authors: Takemoto Tina
Published: May 2014

This essay explores the hidden dimensions of same-sex intimacy and queer sexuality for Japanese Americans incarcerated during World War II. Queer accounts of Japanese American wartime history are rare because of the atypical structure of the incarceration camps, which organized inmates by family units, the prevalence of intergenerational narratives, and dominant themes of loyalty, innocence, and civility. Jiro Onuma, a gay immigrant imprisoned by the federal government at Topaz concentration camp in central Utah, worked in the prison mess hall and was an avid fan of homoerotic male physique magazines. How did this dandy gay bachelor from San Francisco survive the isolation, humiliation, and heteronormativity of imprisonment? The essay recounts the trials and tribulations of looking for Onuma in the mute photographs and other material remains that constitute his archival collection. This inquiry reflects not only my desire to provide a living context for queer artifacts but also grief over the impossibility of fully reanimating these fragmented traces of remembrance. Far from providing a coherent narrative of Onuma's life, this mode of queer speculation demonstrates how affective attachments to the past can lead to unexpected possibilities for engaging with queer history, memory, and the archive.
Material Voices
Authors: Youngblood Stephanie
Published: May 2014

This article takes up the intersection of AIDS testimony, lyric poetry, and gay male sexuality in Frank Bidart's poetry. Using Douglas Crimp's discussion of the politics of AIDS aesthetics as a starting point, I focus on Bidart's 1997 collection of poems, Desire, to consider how lyric voice engages the complexities of queer sexuality in the context of AIDS. I argue that Bidart's lyric dramatizes the relationship between apostrophe and the queer body, drawing attention both to the rhetorical dimensions of embodiment and to the material dimensions of rhetoric. Read in relation to Leo Bersani's analysis of gay male desire and subjectivity, Bidart's work illuminates that the self-present human voice on which testimony seems to rely is itself a rhetorical figure whose grounding in the body can never be fully located or made distinct from its own figural status. Through this simultaneous reliance on and challenge to lyric voice, Bidart engages the specific demands that the AIDS crisis places on testimony while reminding us that desire undermines even as it sustains testimony's imperatives. His poetry thus complicates both the centrality of voice in lyric studies and the seemingly necessary association between voice and transparent subjectivity that has emerged as a subject of contention in American poetry studies.
Defects in the synthetic pathway prevent DIF-1 mediated stalk lineage specification cascade in the non-differentiating social amoeba, Acytostelium subglobosum
Authors: Mohri Kurato , Hata Takashi , Kikuchi Haruhisa , Oshima Yoshiteru , Urushihara Hideko
Published: May 2014

Separation of somatic cells from germ-line cells is a crucial event for multicellular organisms, but how this step was achieved during evolution remains elusive. In Dictyostelium discoideum and many other dictyostelid species, solitary amoebae gather and form a multicellular fruiting body in which germ-line spores and somatic stalk cells differentiate, whereas in Acytostelium subglobosum, acellular stalks form and all aggregated amoebae become spores. In this study, because most D. discoideum genes known to be required for stalk cell differentiation have homologs in A. subglobosum, we inferred functional variations in these genes and examined conservation of the stalk cell specification cascade of D. discoideum mediated by the polyketide differentiation-inducing factor-1 (DIF-1) in A. subglobosum. Through heterologous expression of A. subglobosum orthologs of DIF-1 biosynthesis genes in D. discoideum, we confirmed that two of the three genes were functional equivalents, while DIF-methyltransferase (As-dmtA) involved at the final step of DIF-1 synthesis was not. In fact, DIF-1 activity was undetectable in A. subglobosum lysates and amoebae of this species were not responsive to DIF-1, suggesting a lack of DIF-1 production in this species. On the other hand, the molecular function of an A. subglobosum ortholog of DIF-1 responsive transcription factor was equivalent with that of D. discoideum and inhibition of polyketide synthesis caused developmental arrest in A. subglobosum, which could not be rescued by DIF-1 addition. These results suggest that non-DIF-1 polyketide cascades involving downstream transcription factors are required for fruiting body development of A. subglobosum.
BAG-1M regulates keratin-associated Hsp70 chaperoning of aPKC in intestinal cells under inflammatory signaling
Authors: Mashukova Anastasia , Kozhekbaeva Zhanna , Forteza Radia , Dulam Vipin , Figueroa Yolanda , Warren Robert , Salas Pedro J.
Published: May 2014

Atypical PKC (ι/λ and ζ) is a key player in the acquisition of epithelial polarity and participates in other signaling cascades including NF-kB control. This kinase is post-translationally regulated by Hsp70-mediated refolding. Previous work has shown that such a chaperoning activity is specifically localized on keratin intermediate filaments. This work was performed with the goal of identifying the molecule(s) blocking Hsp70 activity on keratin filaments in inflammation. A transcriptional screen allowed us to focus on BAG-1, a multi-functional protein which assists Hsp70 in nucleotide exchange, but also blocks its activity at higher concentrations. We found the BAG-1M isoform upregulated 3 fold under TNFα stimulation in Caco-2 cells and up to 6 fold in mouse enterocytes under DSS colitis. BAG-1M but not other isoforms, was found to copurify with intermediate filaments and block Hsp70 activity in the keratin fraction but not in the soluble fraction within the range of concentrations found in epithelial cells. BAG-1M constitutive expression decreased p-aPKC. BAG-1 knockdown, conversely, blocked the TNFα-induced decreased levels of p-aPKC. We conclude that BAG-1M mediates Hsp70 inhibition downstream of NF-kB.
Helix-sense-selective Degradation of Poly[4-dodecyloxy-3,5-bis(hydroxymethyl)phenylacetylene] by Selective Photocyclic Aromatization (SCAT) Using Circularly Polarized Light (CPL)
Authors: Miyata Mari , Teraguchi Masahiro , Endo Hiromichi , Kaneko Takashi , Aoki Toshiki
Published: May 2014

Helix-sense-selective photodegaradation of poly[4-dodecyloxy-3,5-bis(hydroxymethyl)phenylacetylene] (poly(DoDHPA)) in membrane state was achieved by selective photocyclic aromatization (SCAT) using single-handed circularly polarized light (CPL). This is the first example of kinetic optical resolution of helical polymers by using CPL.