bluuebunny/crossref_metadata_2025 huggingface dataset:
HDACs Regulate miR-133a Expression in Pressure Overload–Induced Cardiac Fibrosis
Authors: Renaud Ludivine , Harris Lillianne G. , Mani Santhosh K. , Kasiganesan Harinath , Chou James C. , Baicu Catalin F. , Van Laer An , Akerman Adam W. , Stroud Robert E. , Jones Jeffrey A. , Zile Michael R. , Menick Donald R.
Published: September 2015

Background—

MicroRNAs (miRNAs) and histone deacetylases (HDACs) serve a significant role in the pathogenesis of a variety of cardiovascular diseases. The transcriptional regulation of miRNAs is poorly understood in cardiac hypertrophy. We investigated whether the expression of miR-133a is epigenetically regulated by class I and IIb HDACs during hypertrophic remodeling.

Methods and Results—

Transverse aortic constriction (TAC) was performed in CD1 mice to induce pressure overload hypertrophy. Mice were treated with class I and IIb HDAC inhibitor (HDACi) via drinking water for 2 and 4 weeks post TAC. miRNA expression was determined by real-time polymerase chain reaction. Echocardiography was performed at baseline and post TAC end points for structural and functional assessment. Chromatin immunoprecipitation was used to identify HDACs and transcription factors associated with miR-133a promoter. miR-133a expression was downregulated by 0.7- and 0.5-fold at 2 and 4 weeks post TAC, respectively, when compared with vehicle control (
P
<0.05). HDAC inhibition prevented this significant decrease 2 weeks post TAC and maintained miR-133a expression near vehicle control levels, which coincided with (1) a decrease in connective tissue growth factor expression, (2) a reduction in cardiac fibrosis and left atrium diameter (marker of end-diastolic pressure), suggesting an improvement in diastolic function. Chromatin immunoprecipitation analysis revealed that HDAC1 and HDAC2 are present on the miR-133a enhancer regions.

Conclusions—

The results reveal that HDACs play a role in the regulation of pressure overload–induced miR-133a downregulation. This work is the first to provide insight into an epigenetic-miRNA regulatory pathway in pressure overload–induced cardiac fibrosis.
Prevalence and Impact of Chagas Disease Among Latin American Immigrants With Nonischemic Cardiomyopathy in Los Angeles, California
Authors: Traina Mahmoud I. , Sanchez Daniel R. , Hernandez Salvador , Bradfield Jason S. , Labedi Mohamed R. , Ngab Tarik A. , Steurer Frank , Montgomery Susan P. , Meymandi Sheba K.
Published: September 2015

Background—

Chagas disease is a well-known cause of cardiomyopathy in Latin America; however, 300 000 individuals are estimated to have Chagas disease in the United States. This study examined the prevalence and impact of Chagas cardiomyopathy (CCM) in a US population. We hypothesized that patients with CCM would have increased morbidity and mortality when compared with patients with non-CCM.

Methods and Results—

This is a single-center, prospective cohort study. Enrollment criteria were new diagnosis of nonischemic cardiomyopathy (left ventricular ejection fraction ≤40%) and previous residence in Latin America for at least 12 months. Serological testing for
Trypanosoma cruzi
was performed at enrollment. The primary end point was all-cause mortality or heart transplantation. The secondary end point was heart failure–related hospitalization. A total of 135 patients were enrolled, with a median of 43 months of follow-up. Chagas disease was diagnosed in 25 (19%) patients. The primary end point occurred in 9 patients (36%) in the CCM group and in 11 patients (10%) in the non-CCM group (hazard ratio [HR], 4.46; 95% confidence interval, 1.8–10.8;
P
=0.001). The secondary end point occurred in 13 patients (52%) in the CCM group and in 35 patients (32%) in the non-CCM group (HR, 2.22; 95% confidence interval, 1.2–4.2;
P
=0.01).

Conclusions—

There is a high prevalence of Chagas disease among Latin American immigrants diagnosed with nonischemic cardiomyopathy in Los Angeles. Advanced CCM portends a poor prognosis and is associated with increased all-cause mortality/heart transplantation and heart failure–related hospitalization.
Prognostic Significance of Resting Heart Rate and Use of β-Blockers in Atrial Fibrillation and Sinus Rhythm in Patients With Heart Failure and Reduced Ejection Fraction
Authors: Li Shi-Jun , Sartipy Ulrik , Lund Lars H. , Dahlström Ulf , Adiels Martin , Petzold Max , Fu Michael
Published: September 2015

Background—

In heart failure and reduced ejection fraction, the prognostic role of heart rate (HR) in atrial fibrillation (AF) is unknown and the effectiveness of β-blockers has recently been questioned in AF.

Methods and Results—

A total of 18 858 patients with heart failure and reduced ejection fraction registered with Swedish Heart Failure Registry were included in this study: patients with sinus rhythm (SR; n=11 466) and patients with AF (n=7392). The outcome measure was all-cause mortality. Compared with HR ≤60 beats per minute, the adjusted hazard ratios for mortality in SR were 1.26 for HR=61 to 70 beats per minute, 1.37 for HR=71 to 80 beats per minute, 1.52 for HR=81 to 90 beats per minute, 1.63 for HR=91 to 100 beats per minute, and 2.69 for HR >100 beats per minute. However, in AF, the hazard ratio increased only for HR >100 beats per minute (1.30;
P
=0.001). β-blocker use was associated with reduced mortality in SR (hazard ratio, 0.77;
P
=0.011) and in AF (hazard ratio, 0·71;
P
<0.001). For β-blocker use in SR, the hazard ratio gradually increased with HR increment, whereas in AF, the hazard ratio significantly increased only for HR >100 beats per minute (1.29;
P
=0.003) compared with HR ≤60 beats per minute.

Conclusions—

In patients with heart failure and reduced ejection fraction, a higher HR was associated with increased mortality in SR, but in AF, this is true only for HR >100 beats per minute. β-blocker use was associated with reduced mortality both in SR and in AF.
Enhancing the Prediction of 30-Day Readmission After Percutaneous Coronary Intervention Using Data Extracted by Querying of the Electronic Health Record
Authors: Wasfy Jason H. , Singal Gaurav , O’Brien Cashel , Blumenthal Daniel M. , Kennedy Kevin F. , Strom Jordan B. , Spertus John A. , Mauri Laura , Normand Sharon-Lise T. , Yeh Robert W.
Published: September 2015

Background—

Early readmission after percutaneous coronary intervention is an important quality metric, but prediction models from registry data have only moderate discrimination. We aimed to improve ability to predict 30-day readmission after percutaneous coronary intervention from a previously validated registry-based model.

Methods and Results—

We matched readmitted to non-readmitted patients in a 1:2 ratio by risk of readmission, and extracted unstructured and unconventional structured data from the electronic medical record, including need for medical interpretation, albumin level, medical nonadherence, previous number of emergency department visits, atrial fibrillation/flutter, syncope/presyncope, end-stage liver disease, malignancy, and anxiety. We assessed differences in rates of these conditions between cases/controls, and estimated their independent association with 30-day readmission using logistic regression conditional on matched groups. Among 9288 percutaneous coronary interventions, we matched 888 readmitted with 1776 non-readmitted patients. In univariate analysis, cases and controls were significantly different with respect to interpreter (7.9% for cases and 5.3% for controls;
P
=0.009), emergency department visits (1.12 for cases and 0.77 for controls;
P
<0.001), homelessness (3.2% for cases and 1.6% for controls;
P
=0.007), anticoagulation (33.9% for cases and 22.1% for controls;
P
<0.001), atrial fibrillation/flutter (32.7% for cases and 28.9% for controls;
P
=0.045), presyncope/syncope (27.8% for cases and 21.3% for controls;
P
<0.001), and anxiety (69.4% for cases and 62.4% for controls;
P
<0.001). Anticoagulation, emergency department visits, and anxiety were independently associated with readmission.

Conclusions—

Patient characteristics derived from review of the electronic health record can be used to refine risk prediction for hospital readmission after percutaneous coronary intervention.
Persistently Altered Brain Mitochondrial Bioenergetics After Apparently Successful Resuscitation From Cardiac Arrest
Authors: Kilbaugh Todd J. , Sutton Robert M. , Karlsson Michael , Hansson Magnus J. , Naim Maryam Y. , Morgan Ryan W. , Bratinov George , Lampe Joshua W. , Nadkarni Vinay M. , Becker Lance B. , Margulies Susan S. , Berg Robert A.
Published: September 2015

Background

Although advances in cardiopulmonary resuscitation have improved survival from cardiac arrest (
CA
), neurologic injury persists and impaired mitochondrial bioenergetics may be critical for targeted neuroresuscitation. The authors sought to determine if excellent cardiopulmonary resuscitation and postresuscitation care and good traditional survival rates result in persistently disordered cerebral mitochondrial bioenergetics in a porcine pediatric model of asphyxia‐associated ventricular fibrillation
CA
.

Methods and Results

After 7 minutes of asphyxia, followed by ventricular fibrillation, 5 female 1‐month‐old swine (4 sham) received blood pressure–targeted care: titration of compression depth to systolic blood pressure of 90 mm Hg and vasopressor administration to a coronary perfusion pressure >20 mm Hg. All animals received protocol‐based vasopressor support after return of spontaneous circulation for 4 hours before they were killed. The primary outcome was integrated mitochondrial electron transport system (
ETS
) function.
CA
animals displayed significantly decreased maximal, coupled oxidative phosphorylating respiration (

OXPHOS
CI

+

CII

) in cortex (
P
<0.02) and hippocampus (
P
<0.02), as well as decreased phosphorylation and coupling efficiency (cortex,
P
<0.05; hippocampus,
P
<0.05). Complex I– and complex
II
–driven respiration were both significantly decreased after
CA
(cortex:

OXPHOS
CI

P
<0.01,

ETS
CII

P
<0.05; hippocampus:

OXPHOS
CI

P
<0.03,

ETS
CII

P
<0.01). In the hippocampus, there was a significant decrease in maximal uncoupled, nonphosphorylating respiration (

ETS
CI

+

CII

), as well as a 30% reduction in citrate synthase activity (
P
<0.04).

Conclusions

Mitochondria in both the cortex and hippocampus displayed significant alterations in respiratory function after
CA
despite excellent cardiopulmonary resuscitation and postresuscitation care in asphyxia‐associated ventricular fibrillation
CA
. Analysis of integrated
ETS
function identifies mitochondrial bioenergetic failure as a target for goal‐directed neuroresuscitation after
CA
.
IACUC
Protocol:
IAC
13‐001023.
The Text of Aristotle’s Poetics in the Codex Parisinus Graecus 2038
Authors: Tarán Leonardo
Published: September 2015

This article analyzes the text of Aristotle’sPoeticsin Parisinus Graecus 2038. There have been recent attempts to consider that thisms, written around 1470 by Andronicos Callistos, contains primary readings. One must distinguish readings which are based on the scribe’s analysis of the context, many of which coincide with those of the Arabic translation, from other cases where Andronicos tried to improve on readings of the paradosis. In the latter case, his attempts are nothing but either inferior readings orlectiones faciliores. This paper is especially concerned with Richard Janko’s review of Tarán-Gutas’ 2012 edition of thePoetics(Brill). Centanni, Janko, and McOsker are now the main proponents of the reevaluation of Parisinus 2038 and the text of the Aldine edition of 1508. The author considers that such an approach is detrimental to the study of this difficult work.
Distilling a Value Theory of Ideology from Volume Three of Capital
Authors: Best Beverley
Published: September 2015

This discussion is a reformulation of ideology-critique from the point of view of Marx’s theory of the value form. This rethinking of ideology – a formulation I call a value theory of ideology – is carried out through a reading of Marx’s analysis of the capitalist perceptual economy articulated most systematically in Volume iii of Capital. In the course of this ‘rethinking’ I also revisit several concepts that have become associated with Marxian ideology-critique and which are often presented as grounds for the latter’s dismissal: inverted appearance, false consciousness, economism, and the base-superstructure metaphor.
Global Workers’ Rights through Capitalist Institutions?
Authors: Kumar Ashok
Published: September 2015

InWorkers, Unions, and Global Capitalism: Lessons from India, Rohini Hensman maintains that globalisation has afforded workers new opportunities for confronting capitalist exploitation. Using India as a point of departure, Hensman highlights globalisation as paradoxical, challenging anti-globalisers and the globalisation-as-imperialism thesis, to argue that capital’s toilers are now becoming its gravediggers. This analysis also explains why the World Trade Organization (wto) is so appealing to Hensman: a quintessence of capitalism’s contradictions. Hensman argues for both transnational solidarity and independent trade unions, embodied in the ‘employees’ unions’ of India, as well as in favour of thewto’s ‘social clause’ amendment, in which the global exploiter is transformed into an arbiter of workers’ rights. The review maintains that the terms of Hensman’s twin position are impossible to reconcile. It evinces an underlying contradiction between opportunistic statism and a conception of revolutionary strategy predicated on action ‘from below’.
Jesus at the Crossroads of Inference and Imagination
Authors: Ryan Jordan J.
Published: September 2015

A significant re-evaluation of the historiographical methods and approaches used in historical Jesus research has been underway in recent years. Some scholars have begun to look to social memory theory for a way forward. Although social memory theory provides some valuable insights, a solid methodological foundation is still lacking. The intention of this article is to advance the discussion by drawing attention to R.G. Collingwood’s contributions to the philosophy of history and historiography in The Idea of History (1946). In particular, I will discuss his historiographical principles of inference, evidence, question and answer, historical imagination, along with his critique of ‘scissors-and-paste’. These principles have the potential to form the foundation of a theoretically grounded historiographical practice in Jesus research.
Results of a botanical expedition to Mount Roraima, Guyana. II. Lichens

Authors: Sipman H. J. M. , Aptroot A.
Published: September 2015

Lichen exploration of the Upper Mazaruni District, Guyana yielded 273 species, of which 179 were found for the first time in the Guianas and 13 were as yet undescribed. A list of all taxa encountered is presented, with indications of habitat and distribution in the investigated area as well as first descriptions for the following 7 species: Buellia aptrootii, Byssoloma farkasii, Myriotrema guianense, M. neofrondosum, M. subdactyliferum, Ocellularia astrolucens, and Thelotrema albomaculatum. Mazosia bambusae is recorded for the first time from the Neotropics. The richest areas for lichens appear to be the rocky tablelands with scrub vegetation on top of the lower mountains. The slopes of Mount Roraima are of special interest because they support some montane species which are unlikely to be found elsewhere in the Guianas; otherwise they are less rich in lichens, probably because of the high humidity, which favours bryophyte growth.
Threatened bryophytes of the neotropical rain forest: a status report
Authors: Gradstein S. Rob
Published: September 2015

Tropical deforestation, inevitably, leads to the local loss of bryophyte species. Recent studies show that the degree of species loss may vary considerably and depends on the scale or amount of habitat change that has occurred. Predictably, the shade epiphytes are most seriously affected by disturbance. An estimated 10% of the bryophyte species of neotropical rain forests are under threat. Based on data from recent monographs, a first list of 19 endangered and 27 rare species of these forests is presented. Critical areas for threatened species include Costa Rica and Panama, the Greater Antilles, the Chocó, southeastern Brazil, and parts of Amazonia. Protection of as much as possible of the remaining natural rain forest area seems the best approach to the conservation of the tropical bryophyte flora.
MEMOIR OF THE III SIMPOSIO LATINOAMERICANO DE BRIOLOGIA

Authors: Neotrópico Briología En el
Published: September 2015

Botanical history has recorded significant contributions of bryology to its conceptual development and to man’s scientific knowledge. The discovery of sexual chromosomes in plants by Allen and the production of the first polyploids by Wettstein are but two scientific achievments in which bryophytes had an outstanding role. Currently, their use in environmental monitoring and the identification of active principles, make bryophytes objects of great pragmatic interest.
A checklist of the bryophytes of Chiapas, Mexico
Authors: Bourell Mona
Published: September 2015

The vascular flora of Chiapas, Mexico, has been the subject of a long term study by Dennis Breedlove of the California Academy of Sciences. This has stimulated a related project dealing with the bryophyte flora of the region. A collecting expedition in 1988 generated 1420 collections of bryophytes. Specialists from 13 institutions assisted with identifications. Approximately 70% of the collections have been determined. Checklists of species of bryophytes of Chiapas are presented. These lists are based on collections at CAS and literature citations. A total of 364 species of mosses and 310 species of hepatics and hornworts are reported from Chiapas.
Aspidistra guizhouensis (Asparagaceae), a new species from Guizhou, China
Authors: Liu Anli , He Shunzhi , Xu Wenfen
Published: September 2015

Aspidistra guizhouensis S.Z.He & W.F.Xu, a new species of Aspidistra from Guizhou province, China, is described, illustrated and a line drawing of the species is provided. Aspidistra guizhouensis is similar to the widespread species Aspidistra retusa K.Y.Lang & S.Z.Huang and Aspidistra sichuanensis K.Y.Lang & Z.Y.Zhu. The karyotype of this species is analysed.
Three new and two known free-living marine nematode species of the family Ironidae from the East China Sea
Authors: CHEN YU ZHEN , GUO YU QING
Published: September 2015

Three new and two known species of free-living marine nematodes of the family Ironidae from the East China Sea are described and illustrated. Conilia sinensis sp. nov. is identified by the relatively large body size (1883–2399 µm); the well developed lips; the number, shape and length of spicule (single and striated, length 87–100 µm as arc); the shape of telamon; the number of supplements (1). Pheronous donghaiensis sp. nov. is characterized by its sharp tail point; caudal gland absent; buccal cavity armed with four big solid teeth and rows of minute denticles; spicules stout, with central septum at proximal end, male caudal region with two rows of small conical subventral papillae. Trissonchulus latispiculum sp. nov. can be distinguished by its head not set off from remaining body, tail short and blunt, buccal cavity with minute denticles, spinneret opening slightly ventrally, spicule broad and alate with central septum and head on proximal end. Trissonchulus benepapillosus (Schulz, 1935) and Trissonchulus oceanus Cobb 1920 which are first reported from China, are redescribed in detail with emphasis on new or hitherto poorly described morphological features. Types are deposited in the Institute of Oceanology, Chinese Academy of Sciences.
First records of Ungla Navás (Neuroptera: Chrysopidae) from Venezuela, with descriptions of seven new species
Authors: SOSA FRANCISCO
Published: September 2015

Ungla Navás is a small and relatively unstudied genus of Neotropical Chrysopini (Neuroptera: Chrysopidae: Chrysopinae) from Central and South America. Here, the genus is reported from Venezuela for the first time, and seven new species are described: Ungla demarmelsi sp. nov.; Ungla diazi sp. nov.; Ungla curimaguensis sp. nov.; Ungla martinsi sp. nov.; Ungla nigromaculifrons sp. nov.; Ungla rubricosa sp. nov.; and Ungla yutajensis sp. nov.
Review of the Ambrysus stali La Rivers species complex (Heteroptera: Nepomorpha: Naucoridae) with the description of a new species from Mesoamerica
Authors: SITES ROBERT W. , REYNOSO-VELASCO DANIEL
Published: September 2015

The Neotropical Ambrysus stali La Rivers species complex is reviewed and includes A. bifidus La Rivers & Nieser, A. scolius La Rivers, A. stali La Rivers, and A. tricuspis La Rivers. Ambrysus oblongulus Montandon is removed as a member of this complex. Features uniting these species are related to male genitalia and associated structures. Ambrysus maya n. sp. is the fifth species in the complex and is described from Belize, Guatemala, and Mexico based on specimens from recent collecting and museum collections.
Applying Advanced Ground-Based Remote Sensing in the Southeast Asian Maritime Continent to Characterize Regional Proficiencies in Smoke Transport Modeling
Authors: Campbell James R. , Ge Cui , Wang Jun , Welton Ellsworth J. , Bucholtz Anthony , Hyer Edward J. , Reid Elizabeth A. , Chew Boon Ning , Liew Soo-Chin , Salinas Santo V. , Lolli Simone , Kaku Kathleen C. , Lynch Peng , Mahmud Mastura , Mohamad Maznorizan , Holben Brent N.
Published: September 2015

This work describes some of the most extensive ground-based observations of the aerosol profile collected in Southeast Asia to date, highlighting the challenges in simulating these observations with a mesoscale perspective. An 84-h WRF Model coupled with chemistry (WRF-Chem) mesoscale simulation of smoke particle transport at Kuching, Malaysia, in the southern Maritime Continent of Southeast Asia is evaluated relative to a unique collection of continuous ground-based lidar, sun photometer, and 4-h radiosonde profiling. The period was marked by relatively dry conditions, allowing smoke layers transported to the site unperturbed by wet deposition to be common regionally. The model depiction is reasonable overall. Core thermodynamics, including land/sea-breeze structure, are well resolved. Total model smoke extinction and, by proxy, mass concentration are low relative to observation. Smoke emissions source products are likely low because of undersampling of fires in infrared sun-synchronous satellite products, which is exacerbated regionally by endemic low-level cloud cover. Differences are identified between the model mass profile and the lidar profile, particularly during periods of afternoon convective mixing. A static smoke mass injection height parameterized for this study potentially influences this result. The model does not resolve the convective mixing of aerosol particles into the lower free troposphere or the enhancement of near-surface extinction from nighttime cooling and hygroscopic effects.
Correcting Daytime Thermal Offset in Unventilated Pyranometers
Authors: Serrano A. , Sanchez G. , Cancillo M. L.
Published: September 2015

A main source of error in solar radiation measurements is the thermal offset inherent to pyranometers. Despite acknowledgment of its importance, its correction has been widely ignored for several decades. This neglect may have caused a generalized underestimation in solar radiation measurements. This study focuses on the correction of this error in solar irradiance measurements. For this aim a plethora of correction models built as a linear combination of several environmental variables related to the ambient temperature and to the incoming radiation were proposed. The models are fitted to experimental measurements obtained during capping events and, finally, their performance is evaluated and compared. The main results indicate that models with only one independent variable moderately correct the thermal offset error. These simple models are useful when no additional instrumentation other than the pyranometer is available. On the other hand, the more complex models show the best performance, with a coefficient of determinationR2over 0.8, an RMSE under 2 W m−2, and an absolute value of mean bias error (MBE) under 0.5 W m−2. Additionally, these models are used to study the differences between nighttime and daytime correction, revealing the unsuitability of using nighttime-fitted models to correct the daytime thermal offset. The general validity of the models is tested by their application to two different pyranometers. Results indicate that, whereas the factors involved in the best-performing models are the same, the values of the loading coefficients differ and therefore must be specifically calculated for each pyranometer.
Impact of Subgrid-Scale Orography on Equatorial Angular Momentum Budget and the Cold Surges in a General Circulation Model
Authors: Mailler Sylvain , Lott François
Published: September 2015

The dynamical relations between equatorial atmospheric angular momentum (EAAM), equatorial mountain torques, and cold surges are analyzed in a general circulation model (GCM). First, the authors show that the global EAAM budget is well closed in the GCM, much better than in the NCEP–NCAR reanalysis. They then confirm that the equatorial torques due to the Tibetan Plateau, the Rockies, and the Andes are well related to the cold surges developing over East Asia, North America, and South America, respectively. For all these mountains, a peak in the equatorial mountain torque components precedes by few days the development of a cold surge, confirming that the cold surge’s “preconditioning” is dynamically driven by large-scale mountains.

The authors also analyze the contribution of the subgrid-scale orography (SSO) parameterizations and find that they contribute substantially to the torques. In experiments where these parameterizations are almost entirely reduced over a given massif, the authors find that the explicit pressure torques produced by that massif largely compensate the reduction in the parameterized torques. On the one hand, this proves that the explicitly resolved equatorial mountain torques are effective dynamical drivers of the flow dynamics, since they are enhanced when a parameterized torque is reduced. On the other hand, this shows that the cold surges can be captured in GCMs, provided that the synoptic conditions prior to their onset are realistic. The compensation between torques is nevertheless not complete and some weakening of the cold surges is found when the parameterized mountain torques are reduced.
Wired to freedom: Life science, public politics, and the case of Cochlear Implantation
Authors: Jepsen Kim Sune , Bertilsson T. Margareta
Published: September 2015

Cochlear Implantation is now regarded as the most successful medical technology. It carries promises to provide deaf/hearing impaired individuals with a technological sense of hearing and an access to participate on a more equal level in social life. In this article, we explore the adoption of cochlear implantations among Danish users in order to shed more light on their social and political implications. We situate cochlear implantation in a framework of new life science advances, politics, and user experiences. Analytically, we draw upon the notion of social imaginary and explore the social dimension of life science through a notion of public politics adopted from the political theory of John Dewey. We show how cochlear implantation engages different social imaginaries on the collective and individual levels and we suggest that users share an imaginary of being “wired to freedom” that involves new access to social life, continuous communicative challenges, common practices, and experiences. In looking at their lives as “wired to freedom,” we hope to promote a wider spectrum of civic participation in the benefit of future life science developments within and beyond the field of Cochlear Implantation. As our empirical observations are largely based in the Scandinavian countries (notably Denmark), we also provide some reflections on the character of the technology-friendly Scandinavian welfare states and the unintended consequences that may follow in the wake of rapid technology implementation of life science in society.
Making Sense of an Unknown Terrain
Authors: Hughes Nicholas D. , Locock Louise , Simkin Sue , Stewart Anne , Ferrey Anne E. , Gunnell David , Kapur Navneet , Hawton Keith
Published: September 2015

Self-harm is common in young people, and can have profound effects on parents and other family members. We conducted narrative interviews with 41 parents and other family members of 38 young people, aged up to 25, who had self-harmed. Most of the participants were parents but included one sibling and one spouse. This article reports experiences of the parent participants. A cross-case thematic analysis showed that most participants were bewildered by self-harm. The disruption to their worldview brought about by self-harm prompted many to undergo a process of “sense-making”—by ruminative introspection, looking for information, and building a new way of seeing—to understand and come to terms with self-harm. Most participants appeared to have been successful in making sense of self-harm, though not without considerable effort and emotional struggle. Our findings provide grounds for a deeper socio-cultural understanding of the impact of self-harm on parents.
Assessment of the Clinical Utility of Glypican 3 as a Serum Marker for the Diagnosis of Hepatocellular Carcinoma
Authors: Jia Xiaobo , Gao Yingtang , Zhai Daokuan , Liu Jiao , Cai Junjun , Wang Yajie , Jing Li , Du Zhi
Published: September 2015

Glypican-3 has been reported to be one of the most promising serum markers for hepatocellular carcinoma. This study aimed to assess the clinical utility of serum glypican 3 for the diagnosis of hepatocellular carcinoma. We recruited consecutive patients on a large scale, 283 with hepatocellular carcinoma, 445 with chronic hepatic diseases, and 162 normal controls, to assess the diagnostic accuracy of serum glypican 3 for hepatocellular carcinoma by enzyme-linked immunosorbent assay. In addition, we further analyzed the relationship between the serum levels of α-fetoprotein and glypican-3 in patients with hepatocellular carcinoma. The results indicated that serum glypican 3 was elevated in patients with hepatocellular carcinoma (0 ng/mL, range = 0-14.0 ng/mL, P = .033) and liver cirrhosis (0 ng/mL, range = 0-12.5 ng/mL, P = .001) compared to the levels in normal control (0 ng/mL, range = 0-4.3 ng/mL), but there was no difference between hepatocellular carcinoma and liver cirrhosis ( P = .097). The area under the curve of the receiver–operating characteristics curve for hepatocellular carcinoma versus all controls was 0.519, with a sensitivity of 39.9%, a specificity of 60.6%, and an optimal cutoff value of 0.002 ng/mL. The positive and negative predictive values were 32.0% and 68.3%, respectively. No significant correlation in serum levels was observed between glypican 3 and α-fetoprotein ( P > .05). The diagnostic sensitivity for hepatocellular carcinoma increased to 72.8% (206 of the 283) when glypican 3 was combined with α-fetoprotein. Glypican 3 was not a promising serum maker for the diagnosis of hepatocellular carcinoma alone, but it could be complementary to α-fetoprotein and elevate the sensitivity of hepatocellular carcinoma diagnosis.
Estimating the molecular evolutionary rates of mitochondrial genes referring to Quaternary ice age events with inferred population expansions and dispersals in Japanese Apodemus
Authors: Suzuki Yutaro , Tomozawa Morihiko , Koizumi Yuki , Tsuchiya Kimiyuki , Suzuki Hitoshi
Published: September 2015

Background

Determining reliable evolutionary rates of molecular markers is essential in illustrating historical episodes with phylogenetic inferences. Although emerging evidence has suggested a high evolutionary rate for intraspecific genetic variation, it is unclear how long such high evolutionary rates persist because a recent calibration point is rarely available. Other than using fossil evidence, it is possible to estimate evolutionary rates by relying on the well-established temporal framework of the Quaternary glacial cycles that would likely have promoted both rapid expansion events and interisland dispersal events.

Results

We examined mitochondrial cytochromeb(Cytb) and control region (CR) gene sequences in two Japanese wood mouse species,Apodemus argenteusandA. speciosus, of temperate origin and found signs of rapid expansion in the population from Hokkaido, the northern island of Japan. Assuming that global warming after the last glacial period 7–10 thousand years before present (kyr BP) was associated with the expansion, the evolutionary rates (sites per million years, myr) ofCytband CR were estimated as 11–16 % and 22–32 %, respectively, forA. argenteus, and 12–17 % and 17–24 %, respectively, forA. speciosus. Additionally, the significant signature of rapid expansion detected in the mtDNA sequences ofA. speciosusfrom the remaining southern main islands, Honshu, Shikoku, and Kyushu, provided an estimatedCytbevolutionary rate of 3.1 %/site/myr under the assumption of a postglacial population expansion event long ago, most probably at 130 kyr BP. Bayesian analyses using the higher evolutionary rate of 11–17 %/site/myr forCytbsupported the recent demographic or divergence events associated with the Last Glacial Maximum. However, the slower evolutionary rate of 3.1 %/site/myr would be reasonable for several divergence events that were associated with glacial periods older than 130 kyr BP.

Conclusions

The faster and slower evolutionary rates ofCytbcan account for divergences associated with the last and earlier glacial maxima, respectively, in the phylogenetic inference of murine rodents. The elevated evolutionary rate seemed to decline within 100,000 years.
1H-pyrrole-2,5-dione-based small molecule-induced generation of mesenchymal stem cell-derived functional endothelial cells that facilitate rapid endothelialization after vascular injury
Authors: Song Byeong-Wook , Kim Il-Kwon , Lee Seahyoung , Choi Eunhyun , Ham Onju , Lee Se-Yeon , Lee Chang Yeon , Park Jun-Hee , Lee Jiyun , Seo Hyang-Hee , Chang Woochul , Yoon Cheesoon , Hwang Ki-Chul
Published: September 2015

Introduction

Despite the success of interventional processes such as drug-eluting stents, complete prevention of restenosis is still hindered by impaired or delayed endothelialization or both. Here, we report that 1H-pyrrole-2,5-dione-based small molecule-generated mesenchymal stem cell-derived functional endothelial cells (MDFECs) facilitated rapid transmural coverage of injured blood vessels.

Methods

Small molecules that induced CD31 expression were screened by principal component analysis (PCA). Rat mesenchymal stem cells (MSCs) were treated with selected small molecules for up to 16 days, and the expression levels of CD90 and CD31 were examined by immunocytochemistry. In vitro functional assays of MDFECs, including tube formation assays and nitric oxide production assays, were performed. After MDFECs (intravenous, 3×106 cells per animal) were injected into balloon-injured rats, neointima formation was monitored for up to 21 days. The endothelial coverage of denuded blood vessels was evaluated by Evans Blue staining. The functionality of repaired blood vessels was evaluated by measuring vasorelaxation and hemodynamic changes. Additionally, derivatives of the selected small molecules were examined for their ability to induce endothelial markers.

Results

PCA indicated that 3-(2,4-dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione effectively induced MDFECs. MDFECs inhibited the neointima formation of denuded blood vessels by facilitating more rapid endothelialization. Further examination indicated that derivatives with a 1H-pyrrole-2,5-dione moiety are important for initiating the endothelial cell differentiation of MSCs.

Conclusions

Small molecules with 1H-pyrrole-2,5-dione as a core structure have great potential to improve the efficacy of MSC-based cell therapy for vascular diseases, such as atherosclerosis and restenosis.
The differential effects of leukocyte-containing and pure platelet-rich plasma (PRP) on tendon stem/progenitor cells - implications of PRP application for the clinical treatment of tendon injuries
Authors: Zhou Yiqin , Zhang Jianying , Wu Haishan , Hogan MaCalus V. , Wang James H-C.
Published: September 2015

Introduction

Platelet-rich plasma (PRP) is widely used to treat tendon injuries in clinics. These PRP preparations often contain white blood cells or leukocytes, and the precise cellular effects of leukocyte-rich PRP (L-PRP) on tendons are not well defined. Therefore, in this study, we determined the effects of L-PRP on tendon stem/progenitor cells (TSCs), which play a key role in tendon homeostasis and repair.

Methods

TSCs isolated from the patellar tendons of rabbits were treated with L-PRP or P-PRP (pure PRP without leukocytes) in vitro, followed by measuring cell proliferation, stem cell marker expression, inflammatory gene expression, and anabolic and catabolic protein expression by using immunostaining, quantitative real-time polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay, respectively.

Results

Cell proliferation was induced by both L-PRP and P-PRP in a dose-dependent manner with maximum proliferation at a 10 % PRP dose. Both PRP treatments also induced differentiation of TSCs into active tenocytes. Nevertheless, the two types of PRP largely differed in several effects exerted on TSCs. L-PRP induced predominantly catabolic and inflammatory changes in differentiated tenocytes; its treatment increased the expression of catabolic marker genes, matrix metalloproteinase-1 (MMP-1), MMP-13, interleukin-1beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α), and their respective protein expression and prostaglandin E2 (PGE2) production. In contrast, P-PRP mainly induced anabolic changes; that is, P-PRP increased the gene expression of anabolic genes, alpha-smooth muscle actin (α-SMA), collagen types I and III.

Conclusions

These findings indicate that, while both L-PRP and P-PRP appear to be “safe” in inducing TSC differentiation into active tenocytes, L-PRP may be detrimental to the healing of injured tendons because it induces catabolic and inflammatory effects on tendon cells and may prolong the effects in healing tendons. On the other hand, when P-PRP is used to treat acutely injured tendons, it may result in the formation of excessive scar tissue due to the strong potential of P-PRP to induce inordinate cellular anabolic effects.
Identification of California Condor Estrogen Receptors 1 and 2 and Their Activation by Endocrine Disrupting Chemicals
Authors: Felton Rachel G. , Steiner Cynthia C. , Durrant Barbara S. , Keisler Duane H. , Milnes Matthew R. , Tubbs Christopher W.
Published: September 2015

Recently, California condors (Gymnogyps californianus) have been reintroduced to coastal regions of California where they feed on marine mammal carcasses. There is evidence that coastal-dwelling condors experience reproductive issues, such as eggshell thinning, likely resulting from exposure to endocrine-disrupting chemicals (EDCs). To address this problem, we have identified and cloned condor estrogen receptors (ESRs) 1 and 2 and characterized their activation by EDCs present in the coastal habitats where condors reside. Dichlorodiphenyltrichloroethane (DDT) and its metabolites all activated ESR1 and ESR2, although their relative potency differed between the receptors. Bisphenol A, dieldrin, trans-nonachlor, and polychlorinated biphenyl 52 (PCB52) moderately activated both ESRs, whereas PCB138 and PCB153 stimulated little to no activation. Overall, EDC activation of condor ESR2, which is the first ESR2 cloned from a raptor species, was greater than that of ESR1. Significant activation of both condor ESRs by EDCs occurred at high concentrations (≥1μM), which are within the range of plasma levels of certain EDCs (eg, dichlorodiphenyldichloroethylene [p'p-DDE]) in coastal-dwelling condors. Finally, phylogenetic analyses of ESRs of 41 avian species identified a single amino acid position in ESR2 under positive selection. Mutation of this amino acid affected receptor activation by EDCs, suggesting the identity of this amino acid may influence EDC sensitivity of avian species. Together, these findings broaden our understanding of EDC interactions with ESRs in avian species. For condors specifically, these data could be used to evaluate EDC exposure risk at future release sites to identify those least likely to compromise the continued recovery of this species.
Splicing Factor Prp8 Interacts With NESAR and Regulates Androgen Receptor in Prostate Cancer Cells
Authors: Wang Dan , Nguyen Minh M. , Masoodi Khalid Z. , Singh Prabhpreet , Jing Yifeng , O'Malley Katherine , Dar Javid A. , Dhir Rajiv , Wang Zhou
Published: September 2015

Androgen receptor (AR) plays a pivotal role in the development of primary as well as advanced castration-resistant prostate cancer. Previous work in our lab identified a novel nuclear export signal (NES) (NESAR) in AR ligand-binding domain essential for AR nucleocytoplasmic trafficking. By characterizing the localization of green fluorescence protein (GFP)-tagged NESAR, we designed and executed a yeast mutagenesis screen and isolated 7 yeast mutants that failed to display the NESAR export function. One of those mutants was identified as the splicing factor pre-mRNA processing factor 8 (Prp8). We further showed that Prp8 could regulate NESAR function using short hairpin RNA knockdown of Prp8 coupled with a rapamycin export assay in mammalian cells and knockdown of Prp8 could induce nuclear accumulation of GFP-tagged AR in PC3 cells. Prp8 expression was decreased in castration-resistant LuCaP35 xenograft tumors as compared with androgen-sensitive xenografts. Laser capture microdissection and quantitative PCR showed Prp8 mRNA levels were decreased in human prostate cancer specimens with high Gleason scores. In prostate cancer cells, coimmunoprecipitation and deletion mutagenesis revealed a physical interaction between Prp8 and AR mainly mediated by NESAR. Luciferase assay with prostate specific antigen promoter-driven reporter demonstrated that Prp8 regulated AR transcription activity in prostate cancer cells. Interestingly, Prp8 knockdown also increased polyubiquitination of endogenous AR. This may be 1 possible mechanism by which it modulates AR activity. These results show that Prp8 is a novel AR cofactor that interacts with NESAR and regulates AR function in prostate cancer cells.
Transatlantic Picture Stories: Experiments in the Antebellum American Comic Strip
Authors: Beringer Alex
Published: September 2015

It is widely assumed that the American comic strip “begins” in the 1890s with the multipanel sequences appearing in Sunday newspapers. This essay challenges this periodization by looking to an archive of humor magazines from the 1850s and 60s. As early as 1852, artists including Frank Bellew, John McLenan, and Augustus Hoppin experimented with the multipanel sequences they encountered in the Francophone “picture story.” However, rather than replicating the Francophone genre, these artists sought to adapt it in ways that conveyed the rhythms and cadences of everyday American life. What emerges from this study is a newly coherent picture of recurring forms, conventions, and themes that constitute a distinctively American style of comic strip. From one perspective, this is a record of visual conventions that would dominate twentieth- and twenty-first-century comics. But it is also a history of visual languages that failed to take hold—lost literacies and potential trajectories in American comics.
“The Ache of the Actual”: Pain and the Aesthetics of US Literary Realism
Authors: Davis Cynthia J.
Published: September 2015

This essay examines the cultural pursuit of a painless ideal as a neglected context for US literary realism. Advances in anesthesia in the final decades of the nineteenth century shared with influential religious ideologies including the New Thought an assumption that a comfortable existence insulated from physical suffering represented the height of civilization. Theories connecting the civilizing process to an intensifying sensitivity to suffering were often adduced to justify the revulsion from physical pain increasingly characteristic of the era. Similarly invested in the eradication of physical suffering as a civilized ideal, sentimentalism deploys suffering instrumentally in the hopes of encouraging empathy as well as personal and political agency. Mediating between these anesthetizing and sentimentalist sensibilities, realists including Edith Wharton, Henry James, and William Dean Howells espouse an aesthetic sensibility premised on a sensitive yet restrained engagement with pain. They thereby challenge the prevalent association of superiority with a sensitive revulsion from pain while simultaneously evincing a deep skepticism about whether exposure to physical suffering could inspire social change. This essay first surveys the medical advances, religious ideologies, and consumerist tendencies that contributed to the burgeoning perception of painlessness as a desirable and increasingly feasible goal before examining the implications of sentimentalist intensifications of pain for identificatory and reformist purposes. It then explores realism as an aesthetic approach that distinguishes itself from these two distrusted alternatives by expressly depoliticizing pain while foregrounding its intrinsic sensitizing value. Analysis of writings by Wharton, James, and especially Howells reveals realism's investment in representing physical suffering as a catalyst for a ruminative, sensitive, and reticent responsiveness that the realists associated with refinement.
Ordering Words, Ordering the Self: Keeping a Livre de Raison in Early Modern Provence, Sixteenth through Eighteenth Centuries
Authors: Luciani Isabelle
Published: September 2015

Among the growing number of domestic writings in Provence from the end of the Middle Ages, livres de raison comprised a heterogeneous corpus, combining elements of account books, family records, journals, and sometimes chronicles. Their writers, men and women from diverse social backgrounds, drew on complex and varying skills. While avoiding any teleology about the supposed “birth of the individual,” this article explores this heterogeneity to interrogate the specific textual and graphic procedures that reveal the subjective forms of the appropriation of the world and self in daily life. The livre de raison inscribes the individual within familial and social ties; at the same time, however, it constructs a space of personal writing where one could turn within oneself. Thus, behind its ordinary appearance and its collective vocation, the livre de raison established, on a daily basis, one's ordering of the world and reflective capacity.
Holy War or Sedition? The Prophetism of Parisian Preachers and Catholic Militancy, 1558–1588
Authors: Amalou Thierry
Published: September 2015

The uses of prophetism—that is, prophetic activities and personas, as well as prophecy itself—by several celebrated Parisian preachers were transformed during the Wars of Religion. The personal charisma of the pulpits' occupants carried less weight than it had during the Middle Ages. By contrast, the collective identity of those preachers who were doctors of theology was affirmed by references to the sacerdotal Judaism of the Levites. As a result of this evolution, the Faculty of Theology came to lead the battle against religious pacification. Reinforcing the analogy between preachers' freedom of speech and that of the biblical prophets transformed the meaning of obedience to the king. At the same time, biblical imaginary promoted the politicization of sermons. Alongside the struggle against irenicism, a theocratic ideology came to oppose the divine right of kings. Prophetic preaching thus became an instrument for legitimating the right of resistance, which found its institutional form in the 1588 Edict of Union.