bluuebunny/crossref_metadata_2025 huggingface dataset:
Golimumab in Patients Affected by Moderate to Severe Psoriatic Arthritis: An Open-Label Study in Thirty-Two Patients Previously Treated with Other Biologics
Authors: Chimenti Maria Sole , Teoli Miriam , Saraceno Rosita , Dattola Annunziata , Ventura Alessandra , Chiricozzi Andrea , Chiaramonte Carlo , Perricone Roberto , Chimenti Sergio
Published: November 2013

Background: Clinical trials have demonstrated the efficacy of golimumab (GLB) in improving the signs and symptoms of psoriatic arthritis (PsA). Objective: The aim of this study was to evaluate the efficacy of GLB in monotherapy in patients affected by PsA with cutaneous involvement unresponsive to other anti-tumor necrosis factor-α (TNF-α) agents. Methods: This study included 32 patients treated with GLB as monotherapy, at a dosage of 50 mg, subcutaneously, every 4 weeks. Patients were divided into 3 groups (A, B, and C) according to their number of previous anti-TNF-α treatments (1, 2, or 3). Clinical and laboratory evaluations were performed at weeks 0, 12, and 24. Results: All patients showed significant improvement of their clinical, inflammatory, and quality of life indexes. Conclusion: Data suggest that GLB can be successful and safe in patients affected by PsA with skin involvement previously treated with other anti-TNF-α agents.
Epidemiologic Factors and Surgical Outcomes in Patients with Nasal Polyposis and Asthma
Authors: Bush Carrie M. , Jang David W. , Champagne Jason P. , Kountakis Stilianos E.
Published: November 2013

Background/Aim: To evaluate the role of epidemiologic factors in surgical outcomes for patients with nasal polyposis (NP) and asthma. Methods: Data was prospectively collected on patients who underwent endoscopic sinus surgery over a 7-year period. Among patients with chronic rhinosinusitis (CRS) with NP and asthma, surgical outcomes were analyzed according to gender and race. Results: Patients with NP and asthma had significantly higher Lund-Kennedy and SNOT-20 scores - pre- and postoperatively - compared to CRS patients without NP or asthma. Both Caucasians and African-Americans in the CRS with NP/asthma group showed a statistically significant improvement at 6 months. Caucasians continued to have a significant improvement at 12 months, whereas African-Americans did not. There were no differences according to gender. Conclusion: In our patient population, African-Americans with NP and asthma had poorer outcomes following functional endoscopic sinus surgery.
Improving Detection of Hypertension in Girls with Turner Syndrome Using Ambulatory Blood Pressure Monitoring
Authors: Fudge Elizabeth B. , Constantacos Cathrine , Fudge James C. , Davenport Marsha
Published: November 2013

Background/Aims: Turner syndrome (TS) is associated with increased mortality due to cardiovascular disease and a dramatically higher rate of aortic dissection. The recognition and treatment of hypertension in this population is critical. We sought to assess the ability to detect blood pressure (BP) abnormalities comparing ambulatory blood pressure monitoring (ABPM) with conventional BP measurement methods. We hypothesized that ABPM would improve detection of hypertension and alter management strategies. Methods: Twenty-three girls with TS underwent BP measurements using an automated oscillometric method and a manual mercury sphygmomanometer. Twenty-four-hour ABPM was performed (Spacelabs 90217, Issaquah, Wash., USA). BP values were compared to normative data based on height and sex for ABPM, and for age, height and sex for automated oscillometric and manual measurements. Results: Five (22%) subjects were found to have ambulatory hypertension (3 of these with severe hypertension). Three subjects had prehypertension using ABPM measurements. Only 1 of the 5 patients with ambulatory hypertension was categorized as hypertensive using manual BP measurements. Twelve subjects (52%) had nocturnal hypertension. ABPM data led to a change in medical management of hypertensive patients with initiation of antihypertensive therapy. Conclusions: ABPM is advantageous in TS, as it improves detection of hypertension, identifies those with non-dipping BP patterns, and changes medical management of patients.
Evaluating the Status of Antiganglioside Antibodies in Children with Guillain-Barré Syndrome
Authors: Hashemilar Mazyar , Barzegar Mohammad , Nikanfar Masoud , Bonyadi Mohammad Reza , Goldust Mohamad , Ramouz Ali , Ebrahimi Faeghe
Published: November 2013

Objective: Antiganglioside antibodies have been reported to play a role in the pathophysiology of Guillain-Barré syndrome (GBS). Methods: This case-control study was designed to evaluate the status of antiganglioside antibodies in children with GBS. The study included 50 patients suffering from GBS as the case group and 30 children as the control group. Clinical information such as demographic data and recent digestive or respiratory infection (within the last month) was collected for all patients, and paraclinical studies including cerebrospinal fluid examination and electrophysiology were conducted by a subspecialized physician. Anti-GM1, anti-GQ1 and anti-GD1a antibodies were measured with ELISA and the EUROLINE method. Results: The mean age of patients in the case and control groups was 5.3 ± 3.8 and 5.4 ± 3.4 years, respectively. With the EUROLINE method, the results obtained for anti-GM1 were significant (p = 0.007); however, the p values for anti-GQ1a and anti-GQ1b were not significant (0.051 vs. 0.94), while with ELISA, comparing all three antibodies in both the case and control groups showed statistically significant results, with a p < 0.05. Conclusion: EUROLINE is a new method used to evaluate antibodies in immune system diseases, but it is not useful for all antibodies specific to GBS, as the analysis was significant with a p value of 0.007 for anti-GM2.
Global Impact of Heparin on Gene Expression Profiles in Neural Cells Infected by Enterovirus 71
Authors: Pourianfar Hamid Reza , Palombo Enzo , Grollo Lara
Published: November 2013

Objectives: Heparan sulphate mimetics, particularly heparin (Hep), have previously been shown to considerably inhibit infection of enterovirus 71 (EV71) in Vero cells. Therefore, in this study, a genome-wide DNA microarray was performed to gain insight into the mechanism(s) of action of Hep against infection of a human neural cell line, SK-N-SH, with a clinical strain of EV71. Methods: This study focused on a selection of EV71-induced genes whose expression profiling was exclusively affected by the antiviral activity of Hep. The selection procedure was performed through a statistical multi-level comparison with the following controls: negative control cells, compound control (cells treated with Hep only), virus control (cells treated with virus only) and treatment control (EV71-infected cells treated with Hep). Results: Overall, of more than 30,000 genes studied, 14 well-known annotated genes were selected that may be targets for the antiviral activity of Hep against EV71 infection in neural cells. For most of these genes, Hep appeared to modulate the impact of EV71 infection on the expression pattern of the genes. Conclusions: The findings of this research may provide initial assistance in new directions for studies to design molecular drug targets against EV71 infection.
Validation of the J-Chronic Total Occlusion Score for Chronic Total Occlusion Percutaneous Coronary Intervention in an Independent Contemporary Cohort
Authors: Nombela-Franco Luis , Urena Marina , Jerez-Valero Miguel , Nguyen Can Manh , Ribeiro Henrique Barbosa , Bataille Yoann , Rodés-Cabau Josep , Rinfret Stéphane
Published: November 2013

Background—

Chronic total occlusion (CTO) recanalization is a complex and technically challenging procedure. The J-CTO score has been proposed to stratify case complexity and procedural success rates. However, the score has never been tested outside the setting of the original study. Moreover, its predictive value when using a hybrid antegrade or retrograde approach is unknown. We investigated the performance of the J-CTO score for predicting procedure complexity and success in an independent contemporary cohort.

Methods and Results—

A total of 209 consecutive patients who underwent CTO recanalization by a high-volume operator were included. Clinical and angiographic data were prospectively collected. The J-CTO score was applied for each patient, and discrimination and calibration were evaluated in the whole cohort, and according to the approach (antegrade 47% and retrograde 53%). Clinical and angiographic differences were noted between the original and studied cohort. The mean J-CTO score was 2.18±1.26, and successful guidewire crossing within 30 minutes and final angiographic success were 44.5% and 90.4%, respectively. The J-CTO score demonstrated good discrimination (
c
statistic, >0.70) and calibration (Hosmer–Lemeshow
P
>0.1) in the whole cohort and for antegrade and retrograde approaches. However, the final success rate was not associated with the J-CTO score.

Conclusions—

In this independent cohort, the J-CTO score showed good discriminatory and calibration capacity for guidewire CTO crossing within 30 minutes but it does not for final success rate. The J-CTO score helps to predict complexity of CTO recanalization, and the simplicity of the score supports the widespread use as a clinical tool.
Serial Observation of Drug-Eluting Absorbable Metal Scaffold
Authors: Waksman Ron , Prati Francesco , Bruining Nico , Haude Michael , Böse Dirk , Kitabata Hironori , Erne Paul , Verheye Stefan , Degen Hubertus , Vermeersch Paul , Di Vito Luca , Koolen Jacques , Erbel Raimund
Published: November 2013

Background—

The drug-eluting absorbable metal scaffold has demonstrated feasibility, safety, and promising clinical and angiographic outcomes at 12 months in human coronary arteries. This study aimed to evaluate the degradation rate and long-term vascular responses to drug-eluting absorbable metal scaffold.

Methods and Results—

BIOSOLVE-I was a multicenter, single-arm, first-in-man trial assessing the safety and performance of drug-eluting absorbable metal scaffold in 46 patients with coronary artery disease. Patients who underwent serial invasive imaging, such as quantitative coronary angiography, intravascular ultrasound, and optical coherence tomography, at 6 and 12 months were included in this study. From postimplantation to follow-up, arterial curvature and angulation were significantly increased by the degradation process. The greatest increase was seen from postimplantation to 6 months. The systolic–diastolic changes of the curvature and angulation gradually improved throughout the follow-up period. At the site of implantation, vasoconstriction (−10% mean reduction) was observed during the acetylcholine test at 6 months. The average percent hyperechogenicity of the scaffolded segments showed a continuous decrease over time, with the most pronounced changes within the first 6 months (from 22.1±7.0% to 15.8±3.7%;
P
<0.001). Struts discernible on optical coherence tomography at 6 and 12 months showed full neointimal coverage, with stabilization of the mean scaffold area from 6 to 12 months. Furthermore, the mean neointimal area (1.55±0.51 versus 1.58±0.34 mm
2
;
P
=0.794) remained unchanged from 6 to 12 months.

Conclusions—

This serial analysis of drug-eluting absorbable metal scaffold confirmed the safety and efficacy of this new device, with vasomotion restoration and continued degradation over time demonstrated by multi-invasive imaging modalities.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01168830.
Inhibition of MicroRNA-92a Prevents Endothelial Dysfunction and Atherosclerosis in Mice
Authors: Loyer Xavier , Potteaux Stéphane , Vion Anne-Clémence , Guérin Coralie L. , Boulkroun Sheerazed , Rautou Pierre-Emmanuel , Ramkhelawon Bhama , Esposito Bruno , Dalloz Marion , Paul Jean-Louis , Julia Pierre , Maccario Jean , Boulanger Chantal M. , Mallat Ziad , Tedgui Alain
Published: November 2013

Rationale for Study:

MicroRNAs (miRNAs) are small noncoding RNAs that regulate protein expression at post-transcriptional level. We hypothesized that a specific pool of endothelial miRNAs could be selectively regulated by flow conditions and inflammatory signals, and as such be involved in the development of atherosclerosis.

Objective:

To identify miRNAs, called atheromiRs, which are selectively regulated by shear stress and oxidized low-density lipoproteins (oxLDL), and to determine their role in atherogenesis.

Methods and Results:

Large-scale miRNA profiling in HUVECs identified miR-92a as an atheromiR candidate, whose expression is preferentially upregulated by the combination of low shear stress (SS) and atherogenic oxLDL. Ex vivo analysis of atheroprone and atheroprotected areas of mouse arteries and human atherosclerotic plaques demonstrated the preferential expression of miR-92a in atheroprone low SS regions. In
Ldlr
−/−
mice, miR-92a expression was markedly enhanced by hypercholesterolemia, in particular in atheroprone areas of the aorta. Assessment of endothelial inflammation in gain- and loss-of-function experiments targeting miR-92a expression revealed that miR-92a regulated endothelial cell activation by oxLDL, more specifically under low SS conditions, which was associated with modulation of Kruppel-like factor 2 (KLF2), Kruppel-like factor 4 (KLF4), and suppressor of cytokine signaling 5. miR-92a expression was regulated by signal transducer and activator of transcription 3 in SS- and oxLDL-dependent manner. Furthermore, specific in vivo blockade of miR-92a expression in
Ldlr
−/−
mice reduced endothelial inflammation and altered the development of atherosclerosis, decreasing plaque size and promoting a more stable lesion phenotype.

Conclusions:

Upregulation of miR-92a by oxLDL in atheroprone areas promotes endothelial activation and the development of atherosclerotic lesions. Therefore, miR-92a antagomir seems as a new atheroprotective therapeutic strategy.
Longitudinal Effects of a Decade of Aging on Carotid Artery Stiffness
Authors: Gepner Adam D. , Korcarz Claudia E. , Colangelo Laura A. , Hom Elizabeth K. , Tattersall Matthew C. , Astor Brad C. , Kaufman Joel D. , Liu Kiang , Stein James H.
Published: November 2013

Background and Purpose—

Arterial stiffening is associated with hypertension, stroke, and cognitive decline; however, the effects of aging and cardiovascular disease risk factors on carotid artery stiffening have not been assessed prospectively in a large multiethnic longitudinal study.

Methods—

Distensibility coefficient and the Young’s elastic modulus (YEM) of the right common carotid artery were calculated at baseline and after a mean of 9.4 (standard deviation [SD], 0.5) years in 2650 participants. Effects of age and cardiovascular disease risk factors were evaluated by multivariable mixed regression and ANCOVA models.

Results—

At baseline, participants were 59.9 (SD, 9.4) years old (53% women; 25% black, 22% Hispanic, 14% Chinese). YEM increased from 1581 (SD, 927) to 1749 (SD, 1306) mm Hg (
P
<0.0001), and distensibility coefficient decreased from 3.1 (SD, 1.3) to 2.7 (SD, 1.1)×10
–3
mm Hg
−1
(
P
<0.001), indicating progressive arterial stiffening. YEM increased more among participants who were aged >75 years old at baseline (
P
<0.0001). In multivariable analyses, older age and less education independently predicted worsening YEM and distensibility coefficient. Stopping antihypertensive medication during the study period predicted more severe worsening of YEM (β=360.2 mm Hg;
P
=0.008). Starting antihypertensive medication after examination 1 was predictive of improvements in distensibility coefficient (β=1.1×10
–4
mm Hg
–1
;
P
=0.024).

Conclusions—

Arterial stiffening accelerates with advanced age. Older individuals experience greater increases in YEM than do younger adults, even after considering the effects of traditional risk factors. Treating hypertension may slow the progressive decline in carotid artery distensibility observed with aging and improve cerebrovascular health.
Nontraumatic Subarachnoid Hemorrhage in Maintenance Dialysis Hospitalizations
Authors: Sakhuja Ankit , Schold Jesse D. , Kumar Gagan , Katzan Irene , Navaneethan Sankar D.
Published: November 2013

Background and Purpose—

Subarachnoid hemorrhage (SAH) is associated with high mortality, and patients on maintenance dialysis have been shown to be at higher risk for stroke including SAH. However, the outcomes of patients on maintenance dialysis with SAH are not well known. This study was designed to look at incidence and outcomes of SAH in those on maintenance dialysis.

Methods—

Using the Nationwide Inpatient Sample Database, hospitalizations with nontraumatic SAH were identified. Age-adjusted incidence rates were calculated by direct standardization to the 2000 US standard population. Logistic regression was used to assess the risk factors for mortality.

Results—

Of an estimated 149 091 hospitalizations with SAH, 1631 patients (10.9%) were on maintenance dialysis. Unadjusted incidence of SAH hospitalizations was higher in maintenance dialysis than in the general population (73.5 versus 11.2 per 100 000 population), and similar results were seen on age-adjusted analysis. The unadjusted all-cause inpatient mortality rate for SAH admissions was higher in maintenance dialysis versus the general population (38.4% versus 21.9%;
P
<0.001). Maintenance dialysis was an independent predictor of mortality (odds ratio, 2.48; 95% confidence interval, 1.85–3.34), although other significant predictors of mortality were similar in both subgroups. Incidence of SAH hospitalizations has been relatively stable during the study period, but mortality seems to be decreasing.

Conclusions—

SAH hospitalizations are more common and associated with higher mortality in patients on maintenance dialysis than in the general population. Although being on maintenance dialysis is an independent predictor for mortality in patients with SAH, other predictors of mortality evaluated in this study are not necessarily different between the 2 groups.
Soluble Urokinase Plasminogen Activator Receptor
Authors: Persson Margaretha , Östling Gerd , Smith Gustav , Hamrefors Viktor , Melander Olle , Hedblad Bo , Engström Gunnar
Published: November 2013

Background and Purpose—

Recent studies indicate that the urokinase system could have an important role in atherogenesis and plaque rupture. The relationships among the soluble urokinase plasminogen activator receptor (suPAR), carotid plaque, and incidence of ischemic stroke and coronary artery disease (CAD) events were studied in a prospective cohort.

Methods—

Occurrence of carotid plaque and plasma levels of suPAR were assessed in 5166 men and women, aged 45 to 68 years, participating in the Malmö Diet and Cancer study. Incidences of ischemic stroke and CAD were monitored during a mean follow-up of 15 years.

Results—

Subjects with carotid plaque had significantly higher levels of suPAR compared with those without carotid plaque. suPAR was associated with increased incidence of ischemic stroke (hazard ratio [HR] for third versus first tertile, 1.50; 95% confidence interval [CI], 1.06–2.11) and CAD (HR, 1.55; 95% CI, 1.13–2.13) after adjustment for risk factors. The risk factor–adjusted HR for ischemic stroke was 2.21 (95% CI, 1.52–3.22) in subjects with carotid plaque and high suPAR (ie, third tertile) and 1.51 (95% CI, 1.05–2.17) in subjects with carotid plaque and low suPAR compared with those without carotid plaque and low suPAR (reference). High levels of suPAR significantly increased the risk of ischemic stroke and CAD in subjects with carotid plaque.

Conclusions—

suPAR is associated with increased occurrence of carotid plaque and increased incidence of ischemic stroke and CAD. Presence of both elevated levels of suPAR and carotid plaque increases the risk of ischemic stroke in an additive way.
Phylogeny of the Cyrtodactylus irregularis species complex (Squamata: Gekkonidae) from Vietnam with the description of two new species
Authors: NGUYEN SANG NGOC , LE THANH-NGAN THI , TRAN THI ANH DAO , ORLOV NIKOLAI L. , LATHROP AMY , MACCULLOCH ROSS D. , LE THUY-DUONG THI , JIN JIE-QIONG , NGUYEN LUAN THANH , NGUYEN TAO THIEN , HOANG DAT DUC , CHE JING , MURPHY ROBERT W. , ZHANG YA-PING
Published: November 2013

The number of described species of bent-toed geckos of the Cyrtodactylus irregularis species complex in Vietnam has increased from one to eight in the last six years. We combined morphological and molecular analyses to explore phylogenetic relationships among all described species in the group. The phylogeny required the description of two new species, Cyrtodactylus phuocbinhensis sp. nov. and Cyrtodactylus taynguyenensis sp. nov. Further, the tree resolved two additional undescribed clades that may also be new species. The species C. bugiamapensis and C. ziegleri were found to require redefinition. Cyrtodactylus phuocbinhensis sp. nov. is characterized by a series of enlarged femoral scales separated from preanal scales while Cyrtodactylus taynguyenensis sp. nov. does not possess enlarged femoral scales. Both new species are distinguished from other congeners by a combination of the following characters: small subcaudal scales, not transversely enlarged; presence (C. phuocbinhensis sp. nov.) or absence (C. taynguyenensis sp. nov.) of enlarged femoral scales; number of preanal pores; and dorsal pattern. Genetic distances between described species and new species were 16.5% and 2.0% in COI and RPL35, respectively, for C. phuocbinhensis sp. nov., and these distances were 18.8% and 2.2% for C. taynguyenensis sp. nov., respectively.
A new species of Charinus Simon, 1892 from northeastern Brazil with comments on the potential distribution of the genus in Central and South Americas (Arachnida: Amblypygi: Charinidae)
Authors: VASCONCELOS ANA CAROLINE OLIVEIRA , GIUPPONI ALESSANDRO PONCE DE LEÃO , FERREIRA RODRIGO LOPES
Published: November 2013

A new species of the genus Charinus Simon, 1892 is described from caves in the Rio Grande do Norte, Brazil. This is the first record of the genus for the state. This paper presents a map of the Charinus species distribution in Brazil with new records and a map of potential distribution of the genus in South and Central Americas. An updated key for Charinus species from Brazil is also presented.
Nutrition Status and Intestinal Permeability in Patients Eligible for Liver Transplantation
Authors: Liboredo Juliana Costa , Vilela Eduardo Garcia , Ferrari Maria de Lourdes de Abreu , Lima Agnaldo Soares , Correia Maria Isabel Toulson Davisson
Published: November 2013

Background: Increased intestinal permeability has been reported in multiple studies of cirrhotic patients, although specific factors associated with this finding have not been fully elucidated. Thus, the aim of this study was to investigate whether there was an association between nutrition status measured by different methods and intestinal permeability in cirrhotic patients who were candidates for liver transplantation. Materials and Methods: The study group comprised 18 cirrhotic patients and 15 healthy controls. Patients' nutrition status was evaluated by Subjective Global Assessment (SGA), anthropometry, dynamometry, and phase angle, which was determined by bioelectrical impedance analysis. Intestinal permeability was assessed by the lactulose/mannitol test. Results: The prevalence of malnutrition showed wide variance between different assessment methods (5.5%–77.8%). Intestinal permeability was significantly higher in cirrhotic patients than in healthy controls. In relation to nutrition status, intestinal permeability and phase angle did not differ significantly between patients who were considered well nourished (median intestinal permeability, 0.010 [range, 0.001–0.198]; median phase angle, 6.0 [range, 4.2–6.9]) and malnourished patients (intestinal permeability, 0.032 [range, 0.002–0.079]; phase angle, 4.8 [range, 2.2–6.1]) by SGA. In addition, no correlation was found between nutrition diagnosis as assessed by different methods, patient age, liver disease severity scores, and laboratory measurements with intestinal permeability. Conclusion: Although intestinal permeability was increased in cirrhotic patients, this finding was not associated with nutrition status.
Survival Differences between Organ Preservation Surgery and Definitive Radiotherapy in Early Supraglottic Squamous Cell Carcinoma
Authors: Arshad Hassan , Jayaprakash Vijayvel , Gupta Vishal , Cohan David M. , Ambujakshan Dildeep , Rigual Nestor R. , Singh Anurag K. , Hicks Wesley L.
Published: November 2013

Objective

Single‐modality treatment, either with organ preservation surgery (OPS) or definitive radiation (RT), is the treatment of choice for patients with early supraglottic squamous cell carcinoma (SGC). However, studies comparing the effectiveness of these 2 techniques are lacking. This study compares the survival outcomes in early SGC patients treated with OPS versus RT.

Study Design

Secondary data analysis.

Setting

Surveillance, Epidemiology and End Results database.

Subjects and Methods

This study included adult patients with early‐stage (T1N0, T2N0) SGC undergoing single‐modality treatment with either OPS (with or without neck dissection [ND]) or RT between 1988 and 2008. Survival analysis was used to compare the overall survival (OS) and disease‐specific survival (DSS) between patients treated with OPS+ND, OPS alone, and RT.

Results

A total of 2631 T1/T2 N0 SGC patients were identified, of whom 167 (6%) were treated with OPS+ND, 186 (7%) with OPS only, and 2278 patients (87%) with definitive RT only. In stage I (T1N0) SGC patients, a significantly better 5‐year DSS was noted for both OPS+ND (81% vs 68%, hazard ratio [HR] = 0.61, P =. 03) and OPS only (82% vs 68%, HR = 0.70, P =. 05) when compared with definitive RT. For stage II (T2N0) patients, only OPS+ND resulted in a significantly better 5‐year DSS (86% vs 60%, HR = 0.31, P <. 001) when compared with patients treated with RT.

Conclusions

Patients with early SGC who underwent OPS+ND had better OS and DSS than patients undergoing RT alone. OPS+ND may be considered a viable and preferred treatment option in these patients.
Experimental design in the context of Tikhonov regularized inverse problems
Authors: Tenorio L , Lucero C , Ball V , Horesh L
Published: November 2013

The method of Tikhonov regularization is commonly used to obtain regularized solutions of ill-posed linear inverse problems. We use its natural connection to optimal Bayes estimators to determine optimal experimental designs that can be used with Tikhonov regularization; they are designed to control a measure of total relative efficiency. We present an iterative/semidefinite programming hybrid method to explore the configuration space efficiently. Two examples from geophysics are used to illustrate the type of applications to which the methodology can be applied.
PML4 facilitates erythroid differentiation by enhancing the transcriptional activity of GATA-1
Authors: Wu Jie , Zhou Li-Quan , Yu Wei , Zhao Zhi-Guo , Xie Xue-Min , Wang Wen-Tian , Xiong Jian , Li Man , Xue Zheng , Wang Xing , Zhang Peng , Mao Bei-Bei , Hao De-Long , Lv Xiang , Liu De-Pei
Published: November 2013

Key Points

PML4 promotes erythroid differentiation in K562, primary erythroid cells, and GATA-1–rescued G1E-ER4 cells, but not in GATA-1–deficient G1E cells. PML4 interacts with GATA-1 and enhances its transcriptional activity by stimulating GATA-1/P300 cooperation and GATA-1 acetylation.
Polyphosphate amplifies proinflammatory responses of nuclear proteins through interaction with receptor for advanced glycation end products and P2Y1 purinergic receptor
Authors: Dinarvand Peyman , Hassanian Seyed Mahdi , Qureshi Shabir H. , Manithody Chandrashekhara , Eissenberg Joel C. , Yang Likui , Rezaie Alireza R.
Published: November 2013

Key Points

Extracellular nuclear proteins H4 and HMGB1 are highly proinflammatory cytokines. Inorganic polyP dramatically amplifies proinflammatory responses of H4 and HMGB1 through the RAGE and P2Y1 receptors.
Growth rate-coordinated transcriptome reorganization in bacteria
Authors: Matsumoto Yuki , Murakami Yoshie , Tsuru Saburo , Ying Bei-Wen , Yomo Tetsuya
Published: November 2013

Background

Cell growth rate reflects an organism’s physiological state and largely relies on the ability of gene expression to respond to the environment. The relationship between cellular growth rate and gene expression remains unknown.

Results

Growth rate-coordinated changes in gene expression were discovered by analyzing exponentially growingEscherichia colicells cultured under multiple defined environments, in which osmotic pressure, temperature and starvation status were varied. Gene expression analyses showed that all 3,740 genes in the genome could be simply divided into three clusters (C1, C2 and C3), which were accompanied by a generic trend in the growth rate that was coordinated with transcriptional changes. The direction of transcriptional change in C1 indicated environmental specificity, whereas those in C2 and C3 were correlated negatively and positively with growth rates, respectively. The three clusters exhibited differentiated gene functions and gene regulation task division.

Conclusions

We identified three gene clusters, exhibiting differential gene functions and distinct directions in their correlations with growth rates. Reverses in the direction of the growth rate correlated transcriptional changes and the distinguished duties of the three clusters indicated how transcriptome homeostasis is maintained to balance the total expression cost for sustaining life in new habitats.
Molecular diagnosis of distal renal tubular acidosis in Tunisian patients: proposed algorithm for Northern Africa populations for the ATP6V1B1, ATP6V0A4 and SCL4A1genes
Authors: Elhayek Donia , Perez de Nanclares Gustavo , Chouchane Slaheddine , Hamami Saber , Mlika Adnène , Troudi Monia , Leban Nadia , Ben Romdane Wafa , Gueddiche Mohamed Neji , El Amri Féthi , Mrabet Samir , Ben Chibani Jemni , Castaño Luis , Haj Khelil Amel , Ariceta Gema
Published: November 2013

Background

Primary distal renal tubular acidosis (dRTA) caused by mutations in the genes that codify for the H + −ATPase pump subunits is a heterogeneous disease with a poor phenotype-genotype correlation. Up to now, large cohorts of dRTA Tunisian patients have not been analyzed, and molecular defects may differ from those described in other ethnicities. We aim to identify molecular defects present in the ATP6V1B1, ATP6V0A4 and SLC4A1 genes in a Tunisian cohort, according to the following algorithm: first, ATP6V1B1 gene analysis in dRTA patients with sensorineural hearing loss (SNHL) or unknown hearing status. Afterwards, ATP6V0A4 gene study in dRTA patients with normal hearing, and in those without any structural mutation in the ATP6V1B1 gene despite presenting SNHL. Finally, analysis of the SLC4A1 gene in those patients with a negative result for the previous studies.

Methods

25 children (19 boys) with dRTA from 20 families of Tunisian origin were studied. DNAs were extracted by the standard phenol/chloroform method. Molecular analysis was performed by PCR amplification and direct sequencing.

Results

In the index cases, ATP6V1B1 gene screening resulted in a mutation detection rate of 81.25%, which increased up to 95% after ATP6V0A4 gene analysis. Three ATP6V1B1 mutations were observed: one frameshift mutation (c.1155dupC; p.Ile386fs), in exon 12; a G to C single nucleotide substitution, on the acceptor splicing site (c.175-1G > C; p.?) in intron 2, and one novel missense mutation (c.1102G > A; p.Glu368Lys), in exon 11. We also report four mutations in the ATP6V0A4 gene: one single nucleotide deletion in exon 13 (c.1221delG; p.Met408Cysfs*10); the nonsense c.16C > T; p.Arg6*, in exon 3; and the missense changes c.1739 T > C; p.Met580Thr, in exon 17 and c.2035G > T; p.Asp679Tyr, in exon 19.

Conclusion

Molecular diagnosis of ATP6V1B1 and ATP6V0A4 genes was performed in a large Tunisian cohort with dRTA. We identified three different ATP6V1B1 and four different ATP6V0A4 mutations in 25 Tunisian children. One of them, c.1102G > A; p.Glu368Lys in the ATP6V1B1 gene, had not previously been described. Among deaf since childhood patients, 75% had the ATP6V1B1 gene c.1155dupC mutation in homozygosis. Based on the results, we propose a new diagnostic strategy to facilitate the genetic testing in North Africans with dRTA and SNHL.
Structure of the S100A4/myosin-IIA complex
Authors: Ramagopal Udupi A , Dulyaninova Natalya G , Varney Kristen M , Wilder Paul T , Nallamsetty Sridevi , Brenowitz Michael , Weber David J , Almo Steven C , Bresnick Anne R
Published: November 2013

Background

S100A4, a member of the S100 family of Ca2+-binding proteins, modulates the motility of both non-transformed and cancer cells by regulating the localization and stability of cellular protrusions. Biochemical studies have demonstrated that S100A4 binds to the C-terminal end of the myosin-IIA heavy chain coiled-coil and disassembles myosin-IIA filaments; however, the mechanism by which S100A4 mediates myosin-IIA depolymerization is not well understood.

Results

We determined the X-ray crystal structure of the S100A4Δ8C/MIIA1908-1923 peptide complex, which showed an asymmetric binding mode for the myosin-IIA peptide across the S100A4 dimer interface. This asymmetric binding mode was confirmed in NMR studies using a spin-labeled myosin-IIA peptide. In addition, our NMR data indicate that S100A4Δ8C binds the MIIA1908-1923 peptide in an orientation very similar to that observed for wild-type S100A4. Studies of complex formation using a longer, dimeric myosin-IIA construct demonstrated that S100A4 binding dissociates the two myosin-IIA polypeptide chains to form a complex composed of one S100A4 dimer and a single myosin-IIA polypeptide chain. This interaction is mediated, in part, by the instability of the region of the myosin-IIA coiled-coil encompassing the S100A4 binding site.

Conclusion

The structure of the S100A4/MIIA1908-1923 peptide complex has revealed the overall architecture of this assembly and the detailed atomic interactions that mediate S100A4 binding to the myosin-IIA heavy chain. These structural studies support the idea that residues 1908–1923 of the myosin-IIA heavy chain represent a core sequence for the S100A4/myosin-IIA complex. In addition, biophysical studies suggest that structural fluctuations within the myosin-IIA coiled-coil may facilitate S100A4 docking onto a single myosin-IIA polypeptide chain.
Light-sheet Bayesian microscopy enables deep-cell super-resolution imaging of heterochromatin in live human embryonic stem cells
Authors: Hu Ying S , Zhu Quan , Elkins Keri , Tse Kevin , Li Yu , Fitzpatrick James A J , Verma Inder M , Cang Hu
Published: November 2013

Background

Heterochromatin in the nucleus of human embryonic cells plays an important role in the epigenetic regulation of gene expression. The architecture of heterochromatin and its dynamic organization remain elusive because of the lack of fast and high-resolution deep-cell imaging tools. We enable this task by advancing instrumental and algorithmic implementation of the localization-based super-resolution technique.

Results

We present light-sheet Bayesian super-resolution microscopy (LSBM). We adapt light-sheet illumination for super-resolution imaging by using a novel prism-coupled condenser design to illuminate a thin slice of the nucleus with high signal-to-noise ratio. Coupled with a Bayesian algorithm that resolves overlapping fluorophores from high-density areas, we show, for the first time, nanoscopic features of the heterochromatin structure in both fixed and live human embryonic stem cells. The enhanced temporal resolution allows capturing the dynamic change of heterochromatin with a lateral resolution of 50-60 nm on a time scale of 2.3 s.

Conclusion

Light-sheet Bayesian microscopy opens up broad new possibilities of probing nanometer-scale nuclear structures and real-time sub-cellular processes and other previously difficult-to-access intracellular regions of living cells at the single-molecule, and single cell level.
Child of the Fire
Authors: Buick Kirsten
Published: November 2013

Child of the Fire is the first book-length examination of the career of the nineteenth-century artist Mary Edmonia Lewis, best known for her sculptures inspired by historical and biblical themes. Throughout this richly illustrated study, Kirsten Pai Buick investigates how Lewis and her work were perceived, and their meanings manipulated, by others and the sculptor herself. She argues against the racialist art discourse that has long cast Lewis’s sculptures as reflections of her identity as an African American and Native American woman who lived most of her life abroad. Instead, by seeking to reveal Lewis’s intentions through analyses of her career and artwork, Buick illuminates Lewis’s fraught but active participation in the creation of a distinct “American” national art, one dominated by themes of indigeneity, sentimentality, gender, and race. In so doing, she shows that the sculptor variously complicated and facilitated the dominant ideologies of the vanishing American (the notion that Native Americans were a dying race), sentimentality, and true womanhood.

Buick considers the institutions and people that supported Lewis’s career—including Oberlin College, abolitionists in Boston, and American expatriates in Italy—and she explores how their agendas affected the way they perceived and described the artist. Analyzing four of Lewis’s most popular sculptures, each created between 1866 and 1876, Buick discusses interpretations of Hiawatha in terms of the cultural impact of Henry Wadsworth Longfellow’s epic poem The Song of Hiawatha; Forever Free and Hagar in the Wilderness in light of art historians’ assumptions that artworks created by African American artists necessarily reflect African American themes; and The Death of Cleopatra in relation to broader problems of reading art as a reflection of identity.
Thickness Distributions and Evolution of Growth Mechanisms of NH4-Illite from The Fossil Hydrothermal System of Harghita Bãi, Eastern Carpathians, Romania
Authors: Bobos Iuliu , Eberl D. D.
Published: November 2013

The crystal growth of NH4-illite (NH4-I) from the hydrothermal system of Harghita Bãi (Eastern Carpathians) was deduced from the shapes of crystal thickness distributions (CTDs). The <2 mm and the <2-0.2 mm fractions of clay samples collected from the argillized andesite rocks consist of NH4-illite-smectite (I-S) interstratified structures (R1, R2, and R3-type ordering) with a variable smectite-layer content. The NH4-I-S (40-5% S) structures were identified underground in a hydrothermal breccia structure, whereas the K-I/NH4-I mixtures were found at the deepest level sampled (-110 m). The percentage of smectite interlayers generally decreases with increasing depth in the deposit. This decrease in smectite content is related to the increase in degree of fracturing in the breccia structure and corresponds to a general increase in mean illite crystal thickness. In order to determine the thickness distributions of NH4-I crystals (fundamental illite particles) which make up the NH4-I-S interstratified structures and the NH4-I/K-I mixtures, 27 samples were saturated with Li and aqueous solutions of PVP-10 to remove swelling and then were analyzed by X-ray diffraction. The profiles for the mean crystallite thickness (Tmean) and crystallite thickness distribution (CTD) of NH4-I crystallites were determined by the Bertaut-Warren-Averbach method using the MudMaster computer code. The Tmean of NH4-I from NH4-I-S samples ranges from 3.4 to 7.8 nm. The Tmean measured for the NH4-I/K-I mixture phase ranges from 7.8 nm to 11.7 nm (NH4-I) and from 12.1 to 24.7 nm (K-I).

The CTD shapes of NH4-I fundamental particles are asymptotic and lognormal, whereas illites from NH4-I/K-I mixtures have bimodal shapes related to the presence of two lognormal-like CTDs corresponding to NH4-I and K-I.

The crystal-growth mechanism for NH4-I samples was simulated using the Galoper code. Reaction pathways for NH4-I crystal nucleation and growth could be determined for each sample by plotting their CTD parameters on an α-ß2 diagram constructed using Galoper. This analysis shows that NH4-I crystals underwent simultaneous nucleation and growth, followed by surface-controlled growth without simultaneous nucleation.
Sex Differences in the Metabolic Syndrome: Implications for Cardiovascular Health in Women
Authors: Pradhan Aruna D
Published: November 2013

BACKGROUND

The metabolic syndrome is a clinical condition characterized by the presence of multiple interrelated risk factors for type 2 diabetes and cardiovascular disease. Component features include dysglycemia, increased blood pressure, increased triglycerides, decreased HDL cholesterol concentrations, and obesity (in particular, abdominal obesity). The underlying biology, optimal diagnostic criteria, and clinical implications, once diagnosed, have been matter for intense debate. Despite these areas of controversy, there is now general consensus that the observed risk factor clustering signifies heightened cardiovascular risk.

CONTENT

The influence of sex on the clinical expression and pathophysiology of the syndrome is underrecognized, and is an issue of increasing importance given the alarming increase in prevalence among young women. This minireview will highlight sex differences in the epidemiology, etiology, biology, and clinical expression of the metabolic syndrome. In particular, key sex differences include distinctions in (a) prevalence of dysglycemia, (b) body fat distribution, (c) adipocyte size and function, (d) hormonal regulation of body weight and adiposity, and (e) the influence of estrogen decline on risk factor clustering.

Accumulated and emerging data convincingly demonstrate that significant heterogeneity exists between men and women developing the metabolic syndrome, in large part related to hormonal regulation of body fat distribution and attendant metabolic abnormalities.
Experiential knowledge and improvisation: Variations on movement, motion, emotion
Authors: Douglas Anne , Coessens Kathleen
Published: November 2013

Improvisation is a way of knowing that is experiential, pivotal to the body’s movement and growth in the world. It allows us to manage constraint and freedom in a rich world of possibility. Within this article we trace a trajectory from improvisation in life to improvisation in
art. By focusing on practitioners who work with improvisation in precise ways in the fields of anthropology, ecology, visual art and music, we explore how improvisation and experiential knowledge are profoundly interconnected. To achieve this, we use the four characteristics of improvisation
developed by anthropologists Ingold and Hallam as a framework for the evaluation of art practices of improvisation including the authors’ own project work. We expand the framework through Dewey’s analysis of art as experience. The article concludes with an evaluation of how the
techniques and processes of improvisation from the case examples may be useful ways to shed light on the workings of experiential knowledge.
Functional constraints, usage, and mental grammars: A study of speakers' intuitions about questions with long-distance dependencies
Authors: Dąbrowska Ewa
Published: November 2013

This paper describes an experimental study which attempts to reconcile two usage based approaches to questions with long distance dependencies (LDDs): the Lexical Template Hypothesis (Dąbrowska 2004, 2008; Verhagen 2005, 2006) and Goldberg's BCI (“Backgrounded Constituents are Islands”) constraint (Goldberg 2006; Ambridge and Goldberg 2008). The study replicates Ambridge and Goldberg's (2008) results supporting the BCI constraint; but it also shows that (1) LDD questions with think and say, the verbs which are part of the hypothesised templates, are judged to be more acceptable than predicted by BCI and (2) BCI cannot explain complementizer effects (why LDD questions with that are judged less acceptable than questions without that). The results also suggest that there are considerable individual differences in speakers' sensitivity to the constraint.

Thus, the two hypotheses are complementary: BCI explains why certain LDD questions are more acceptable than others, and hence accounts for differences in the frequency of prototypical and unprototypical LDD questions, while the lexical template hypothesis explains the effects of the frequency of use on speakers' mental grammars.
Three-dimensional ultrasound of massive macroglossia in a fetus with Beckwith-Wiedemann syndrome
Authors: Bamberg Christian , Hinkson Larry , Longardt Ann Carolin , Rothe Karin , Horn Denise , Henrich Wolfgang
Published: November 2013

We present the prenatal ultrasound findings of massive macroglossia in a fetus with prenatally diagnosed Beckwith-Wiedemann syndrome. Three-dimensional surface mode ultrasound was utilized for enhanced visualization of the macroglossia.
Antagonistic Interaction between Adenosine A2AReceptors and Na+/K+-ATPase-α2Controlling Glutamate Uptake in Astrocytes
Authors: Matos Marco , Augusto Elisabete , Agostinho Paula , Cunha Rodrigo A. , Chen Jiang-Fan
Published: November 2013

Astrocytic glutamate transporter-1 (GLT-I) is critical to control the bulk of glutamate uptake and, thus, to regulate synaptic plasticity and excitotoxicity. GLT-I glutamate uptake is driven by the sodium gradient implemented by Na+/K+-ATPases (NKAs) and the α2subunit of NKA (NKA-α2) is actually linked to GLT-I to regulate astrocytic glutamate transport. We recently found that adenosine A2Areceptors (A2ARs), which control synaptic plasticity and neurodegeneration, regulate glutamate uptake through unknown mechanisms. Here we report that A2AR activation decreases NKA activity selectively in astrocytes to inhibit glutamate uptake. Furthermore, we found a physical association of A2ARs with NKA-α2s in astrocytes, as gauged by coimmunoprecipitation andin situproximity ligation assays, in the cerebral cortex and striatum, two brain regions where A2ARs inhibit the astrocytic glutamate uptake. Moreover, the selective deletion of A2ARs in astrocytes (using Gfa2-A2AR-KO mice) leads to a concurrent increase of both astrocytic glutamate uptake and NKA-α2levels and activity in the striatum and cortex. This coupling of astrocytic A2ARs to the regulation of glutamate transport through modulation of NKA-α2activity provides a novel mechanism linking neuronal activity to ion homeostasis controlling glutamatergic activity, all of which are processes intricately associated with the etiology of several brain diseases.
Auditory Cortical Local Subnetworks Are Characterized by Sharply Synchronous Activity
Authors: Atencio Craig A. , Schreiner Christoph E.
Published: November 2013

In primary auditory cortex (AI), broadly correlated firing has been commonly observed. In contrast, sharply synchronous firing has rarely been seen and has not been well characterized. Therefore, we examined cat AI local subnetworks using cross-correlation and spectrotemporal receptive field (STRF) analysis for neighboring neurons. Sharply synchronous firing responses were observed predominantly for neurons separated by <150 μm. This high synchrony was independent of layers and was present between all distinguishable cell types. The sharpest synchrony was seen in supragranular layers and between regular spiking units. Synchronous spikes conveyed more stimulus information than nonsynchronous spikes. Neighboring neurons in all layers had similar best frequencies and similar STRFs, with the highest similarity in supragranular and granular layers. Spectral tuning selectivity and latency were only moderately conserved in these local, high-synchrony AI subnetworks. Overall, sharp synchrony is a specific characteristic of fine-scale networks within the AI and local functional processing is well ordered and similar, but not identical, for neighboring neurons of all cell types.