bluuebunny/crossref_metadata_2025 huggingface dataset:
Pyrvinium Targets CD133 in Human Glioblastoma Brain Tumor–Initiating Cells
Authors: Venugopal Chitra , Hallett Robin , Vora Parvez , Manoranjan Branavan , Mahendram Sujeivan , Qazi Maleeha A. , McFarlane Nicole , Subapanditha Minomi , Nolte Sara M. , Singh Mohini , Bakhshinyan David , Garg Neha , Vijayakumar Thusyanth , Lach Boleslaw , Provias John P. , Reddy Kesava , Murty Naresh K. , Doble Bradley W. , Bhatia Mickie , Hassell John A. , Singh Sheila K.
Published: July 2015

Purpose: Clonal evolution of cancer may be regulated by determinants of stemness, specifically self-renewal, and current therapies have not considered how genetic perturbations or properties of stemness affect such functional processes. Glioblastoma-initiating cells (GICs), identified by expression of the cell surface marker CD133, are shown to be chemoradioresistant. In the current study, we sought to elucidate the functional role of CD133 in self-renewal and identify compounds that can specifically target this CD133+ treatment-refractory population.

Experimental Design: Using gain/loss-of-function studies for CD133 we assessed the in vitro self-renewal and in vivo tumor formation capabilities of patient-derived glioblastoma cells. We generated a CD133 signature combined with an in silico screen to find compounds that target GICs. Self-renewal and proliferation assays on CD133-sorted samples were performed to identify the preferential action of hit compounds. In vivo efficacy of the lead compound pyrvinium was assessed in intracranial GIC xenografts and survival studies. Lastly, microarray analysis was performed on pyrvinium-treated GICs to discover core signaling events involved.

Results: We discovered pyrvinium, a small-molecule inhibitor of GIC self-renewal in vitro and in vivo, in part through inhibition of Wnt/β-catenin signaling and other essential stem cell regulatory pathways. We provide a therapeutically tractable strategy to target self-renewing, chemoradioresistant, and functionally important CD133+ stem cells that drive glioblastoma relapse and mortality.

Conclusions: Our study provides an integrated approach for the eradication of clonal populations responsible for cancer progression, and may apply to other aggressive and heterogeneous cancers. Clin Cancer Res; 21(23); 5324–37. ©2015 AACR.
Prediction of Response to Neoadjuvant Chemotherapy Using Core Needle Biopsy Samples with the Prosigna Assay
Authors: Prat Aleix , Galván Patricia , Jimenez Begoña , Buckingham Wesley , Jeiranian H. Arthur , Schaper Carl , Vidal Maria , Álvarez Martina , Díaz Sherley , Ellis Catherine , Nuciforo Paolo , Ferree Sean , Ribelles Nuria , Adamo Barbara , Ramón y Cajal Santiago , Peg Vicente , Alba Emilio
Published: July 2015

Purpose: Most hormone receptor (HR)+/HER2− breast cancer patients respond unfavorably to neoadjuvant chemotherapy (NAC); however, genomic tests may identify those patients who are likely to benefit. Using the Prosigna assay, we first evaluated the technical performance of core needle biopsy (CNB) tissues. We then determined whether Prosigna risk of relapse (ROR) score and intrinsic subtype predicted response to NAC in HR+/HER2− patients using CNB samples.

Experimental Design: Using the NanoString's nCounter Dx analysis system and a development tissue sample set, we established tissue requirements and assay output variance. We then evaluated the concordance in subtype and correlation in ROR between CNBs and corresponding surgical resection specimens (SRS) in a second independent sample set. Finally, we analyzed 180 independent CNB samples from HR+/HER2− patients who were treated with NAC and correlated ROR and intrinsic subtype with pathologic response.

Results: Intra- and interbiopsy variabilities were 2.2 and 6.8 ROR units, respectively. Subtype concordance within multiple CNBs was high for the 4- and 3-subtype classifications (k = 0.885 and 0.889, respectively). Correlation in Prosigna ROR score observed between paired CNBs and SRS was high (r ≥ 0.90), and subtype concordance was also high for the 4- and 3-subtype classifications (kappa = 0.81 and 0.91, respectively). Prosigna results obtained from the HR+/HER2− patient samples showed that both ROR (P = 0.047) and intrinsic subtype (OR LumA vs. non-LumA = 0.341, P = 0.037) were significant predictors of response to NAC.

Conclusions: Prosigna ROR and intrinsic subtype are readily obtained from CNB samples in normal practice and reliably predict response to NAC in HR+/HER2− patients. Clin Cancer Res; 22(3); 560–6. ©2015 AACR.
Regulation of the Utilization of Amino Sugars by Escherichia coli and Bacillus subtilis: Same Genes, Different Control
Authors: Plumbridge Jacqueline
Published: July 2015

Amino sugars are dual-purpose compounds in bacteria: they are essential components of the outer wall peptidoglycan (PG) and the outer membrane of Gram-negative bacteria and, in addition, when supplied exogenously their catabolism contributes valuable supplies of energy, carbon and nitrogen to the cell. The enzymes for both the synthesis and degradation of glucosamine (GlcN) and N-acetylglucosamine (GlcNAc) are highly conserved but during evolution have become subject to different regulatory regimes. Escherichia coli grows more rapidly using GlcNAc as a carbon source than with GlcN. On the other hand, Bacillus subtilis, but not other Bacilli tested, grows more efficiently on GlcN than GlcNAc. The more rapid growth on this sugar is associated with the presence of a second, GlcN-specific operon, which is unique to this species. A single locus is associated with the genes for catabolism of GlcNAc and GlcN in E. coli, although they enter the cell via different transporters. In E. coli the amino sugar transport and catabolic genes have also been requisitioned as part of the PG recycling process. Although PG recycling likely occurs in B. subtilis, it appears to have different characteristics.
A Search for Ribonucleic Antiterminator Sites in Bacterial Genomes: Not Only Antitermination
Authors: Gordon Noa , Rosenblum Ronen , Nussbaum-Shochat Anat , Eliahoo Elad , Amster-Choder Orna
Published: July 2015

BglG/LicT-like proteins are transcriptional antiterminators that prevent termination of transcription at intrinsic terminators by binding to ribonucleic antiterminator (RAT) sites and stabilizing an RNA conformation which is mutually exclusive with the terminator structure. The known RAT sites, which are located in intergenic regions of sugar utilization operons, show low sequence conservation but significant structural analogy. To assess the prevalence of RATs in bacterial genomes, we employed bioinformatic tools that describe RNA motifs based on both sequence and structural constraints. Using descriptors with different stringency, we searched the genomes of Escherichiacoli K12, uropathogenic E. coli and Bacillus subtilis for putative RATs. Our search identified all known RATs and additional putative RAT elements. Surprisingly, most putative RATs do not overlap an intrinsic terminator and many reside within open reading frames (ORFs). The ability of one of the putative RATs, which is located within an antiterminator-encoding ORF and does not overlap a terminator, to bind to its cognate antiterminator protein in vitro and in vivo was confirmed experimentally. Our results suggest that the capacity of RAT elements has been exploited during evolution to mediate activities other than antitermination, for example control of transcription elongation or of RNA stability.
Control of Transposon-Mediated Directed Mutation by the Escherichia coli Phosphoenolpyruvate:Sugar Phosphotransferase System
Authors: Saier Jr. Milton H. , Zhang Zhongge
Published: July 2015

The phosphoenolpyruvate:sugar phosphotransferase system (PTS) has been shown to control transport, cell metabolism and gene expression. We here present results supporting the novel suggestion that in certain instances it also regulates the mutation rate. Directed mutations are defined as mutations that occur at higher frequencies when beneficial than when neutral or detrimental. To date, the occurrence of directed point mutations has not been documented and confirmed, but a few examples of transposon-mediated directed mutations have been reported. Here we focus on the first and best-studied example of directed mutation, which involves the regulation of insertion sequence-5 hopping into a specific site upstream of the glpFK glycerol utilization operon in Escherichia coli. This insertional event specifically activates expression of the glpFK operon, allowing the growth of wild-type cells with glycerol as a carbon source in the presence of nonmetabolizable glucose analogues which normally block glycerol utilization. The sugar-transporting PTS controls this process by regulating levels of cytoplasmic glycerol-3-phosphate and cyclic (c)AMP as established in previous publications. Direct involvement of the glycerol repressor, GlpR, and the cAMP receptor protein, Crp, in the regulation of transposon-mediated directed mutation has been demonstrated.
Biofilm Growth of Escherichia coli Is Subject to cAMP-Dependent and cAMP-Independent Inhibition
Authors: Sutrina Sarah L. , Daniel Kia , Lewis Michael , Charles Naomi T. , Anselm Cherysa K.E. , Thomas Na''am , Holder Nikolai
Published: July 2015

We established that Escherichia coli strain 15 (ATCC 9723) produces both curli and cellulose, and forms robust biofilms. Since this strain is wild type with respect to the phosphoenolpyruvate:sugar phosphotransferase system (PTS), it is an ideal strain in which to investigate the effects of the PTS on the biofilm growth of E. coli. We began by looking into the effects of PTS and non-PTS sugars on the biofilm growth of this strain. All the sugars tested tended to activate biofilm growth at low concentrations but to inhibit biofilm growth at high concentrations. Acidification of the medium was an inhibitory factor in the absence of buffer, but buffering to prevent a pH drop did not prevent the inhibitory effects of the sugars. The concentration at which inhibition set in varied from sugar to sugar. For most sugars, cyclic (c)AMP counteracted the inhibition at the lowest inhibitory concentrations but became ineffective at higher concentrations. Our results suggest that cAMP-dependent catabolite repression, which is mediated by the PTS in E. coli, plays a role in the regulation of biofilm growth in response to sugars. cAMP-independent processes, possibly including Cra, also appear to be involved, in addition to pH effects.
Fucose-Mediated Transcriptional Activation of the fcs Operon by FcsR in Streptococcus pneumoniae
Authors: Manzoor Irfan , Shafeeq Sulman , Afzal Muhammad , Kuipers Oscar P.
Published: July 2015

In this study, we explore the impact of fucose on the transcriptome of S. pneumoniae D39. The expression of various genes and operons, including the fucose uptake PTS and utilization operon (fcs operon) was altered in the presence of fucose. By means of quantitative RT-PCR and β-galactosidase analysis, we demonstrate the role of the transcriptional regulator FcsR, present upstream of the fcs operon, as a transcriptional activator of the fcs operon. We also predict a 19-bp putative FcsR regulatory site (5′-ATTTGAACATTATTCAAGT-3′) in the promoter region of the fcs operon. The functionality of this predicted FcsR regulatory site was further confirmed by promoter-truncation experiments, where deletion of half of the FscR regulatory site or full deletion led to the abolition of expression of the fcs operon.
Modeling the Interplay of Pseudomonas putida EIIANtr with the Potassium Transporter KdpFABC
Authors: Wolf S. , Pflüger-Grau K. , Kremling A.
Published: July 2015

The nitrogen phosphotransferase system (PTSNtr) of Pseudomonas putida is a key regulatory device that participates in controlling many physiological processes in a posttranscriptional fashion. One of the target functions of the PTSNtr is the regulation of potassium transport. This is mediated by the direct interaction of one of its components with the sensor kinase KdpD of the two-component system controlling transcription of the kdpFABC genes. From a detailed experimental analysis of the activity of the kdpF promoter in P. putida wild-type and pts mutant strains with varying potassium concentrations, we had highly time-resolved data at hand, describing the influence of the PTSNtr on the transcription of the KdpFABC potassium transporter. Here, this data was used to construct a mathematical model based on a black box approach. The model was able to describe the data quantitatively with convincing accuracy. The qualitative interpretation of the model allowed the prediction of two general points describing the interplay between the PTSNtr and the KdpFABC potassium transporter: (1) the influence of cell number on the performance of the kdpF promoter is mainly by dilution by growth and (2) potassium uptake is regulated not only by the activity of the KdpD/KdpE two-component system (in turn influenced by PtsN). An additional controller with integrative behavior is predicted by the model structure. This suggests the presence of a novel physiological mechanism during regulation of potassium uptake with the KdpFABC transporter and may serve as a starting point for further investigations.
The Bacterial Phosphotransferase System: New Frontiers 50 Years after Its Discovery
Authors: Saier Jr. Milton H.
Published: July 2015

In 1964, Kundig, Ghosh and Roseman reported the discovery of the phosphoenolpyruvate:sugar phosphotransferase system (PTS), which they subsequently proposed might catalyze sugar transport as well as sugar phosphorylation. What we have learned in the 50 years since its discovery is that, in addition to these primary functions, the PTS serves as a complex protein kinase system that regulates a wide variety of transport, metabolic and mutagenic processes as well as the expression of numerous genes. Recent operon- and genome-sequencing projects have revealed novel PTS protein-encoding genes, many of which have yet to be functionally defined. The current picture of the PTS is that of a complex system with ramifications in all aspects of cellular physiology. Moreover, its mosaic evolutionary history is unusual and intriguing. The PTS can be considered to serve many prokaryotes in capacities of communication and coordination, as do the nervous systems of animals.
Annular Lichenoid Dermatitis of Youth: Report of Six New Cases with Review of the Literature
Authors: Di Mercurio Marco , Gisondi Paolo , Colato Chiara , Schena Donatella , Girolomoni Giampiero
Published: July 2015

Background: Annular lichenoid dermatitis of youth (ALDY) is an uncommon disease clinically reminiscent of morphea, annular erythema or mycosis fungoides. Objective: To describe the histological and clinical features of a small series of patients with ALDY and to review the literature. Patients: We describe the clinical and histological features of six patients (age range 7-79 years) with asymptomatic erythematous macules and patches with a red-brownish border and central hypopigmentation, mostly distributed on the groin and flanks. Histologically, all cases showed lichenoid dermatitis limited to the tips of rete ridges, with many intraepidermal CD8+ and some CD4+ T cells. T cell receptor rearrangement was absent in all cases. A total of 44 patients with a consistent clinical and histological picture have been described. The disease is sensitive to topical and/or systemic corticosteroids. Conclusions: ALDY is a unique lichenoid dermatitis for whose diagnosis a clinical-pathological correlation is essential. The disease typically affects young patients, more rarely adults and elderly.
ROS-Dependent Neuroprotective Effects of NaHS in Ischemia Brain Injury Involves the PARP/AIF Pathway
Authors: Yu Qian , Lu Zhihong , Tao Lei , Yang Lu , Guo Yu , Yang Yonghui , Sun Xude , Ding Qian
Published: July 2015

Background/Aims: Stroke is among the top causes of death worldwide. Neuroprotective agents are thus considered as potentially powerful treatment of stroke. Methods: Using both HT22 cells and male Sprague-Dawley rats as in vitro and in vivo models, we investigated the effect of NaHS, an exogenous donor of H2S, on the focal cerebral ischemia-reperfusion (I/R) induced brain injury. Results: Administration of NaHS significantly decreased the brain infarcted area as compared to the I/R group in a dose-dependent manner. Mechanistic studies demonstrated that NaHS-treated rats displayed significant reduction of malondialdehyde content, and strikingly increased activity of superoxide dismutases and glutathione peroxidase in the brain tissues compared with I/R group. The enhanced antioxidant capacity as well as restored mitochondrial function are NaHS-treatment correlated with decreased cellular reactive oxygen species level and compromised apoptosis in vitro or in vivo in the presence of NaHS compared with control. Further analysis revealed that the inhibition of PARP-1 cleavage and AIF translocation are involved in the neuroprotective effects of NaHS. Conclusion: Collectively, our results suggest that NaHS has potent protective effects against the brain injury induced by I/R. NaHS is possibly effective through inhibition of oxidative stress and apoptosis.
Stimulation of Wnt/β-Catenin Signaling to Improve Bone Development by Naringin via Interacting with AMPK and Akt
Authors: Wang Dawei , Ma Wenpu , Wang Fu , Dong Jinlei , Wang Dan , Sun Bo , Wang Bomin
Published: July 2015

Background/Aims: Naringin is a naturally existing compound in citrus fruits and has been elucidated to promote bone development and maintenance. Methods: The biological roles of naringin were investigated in vitro using osteoblast-like UMR-106 cells, and in vivo through performing ovariectomy to mimic osteoporosis in female mice. Since Wnt/β-catenin signaling is involved in osteoblastogenesis, the effect of naringin on Wnt/β-catenin signaling was studied. Results: Naringin promoted the mRNA and protein expressions of β-catenin, and improved Ser552 phosphorylation on β-catenin in UMR-106 cells, which leads to the activation of lymphoid enhancer factor (LEF)/ T-cell factor (TCF) transcription factors. The recruitments of protein kinase B (Akt) inhibitor (Akti-1/2) and AMP-activated protein kinase (AMPK) inhibitor (Dorsomorphin) reduced the influence of naringin on β-catenin phosphorylation, suggesting naringin activates β-catenin via regulating Akt and AMPK. In ovariectomized (OVX) mice naringin treatment improved the bone strength while AMPK and Akt inhibitors partly reversed the effect, which further proved the involvements of Akt and AMPK in the action of naringin in vivo. Conclusion: Our study points to a novel finding on the mechanism of naringin in facilitating bone formation via Akt and AMPK signaling.
MiR-499 Enhances the Cisplatin Sensitivity of Esophageal Carcinoma Cell Lines by Targeting DNA Polymerase β
Authors: Wang Yuanyuan , Feng Jianfang , Zang Wenqiao , Du Yuwen , Chen Xiaonan , Sun Qianqian , Dong Ziming , Zhao Guoqiang
Published: July 2015

Background: Human DNA polymerase β (DNA polymerase β, polβ) is a small monomeric protein essential for short-patch base excision repair (BER). It plays an important role in regulating the sensitivity of tumor cells to chemotherapy. Methods: Luciferase reporter and western blot assays were used to determine whether polβ is a major target of miR-499. CCK-8, colony-forming survival and in vivo tumor growth assays were conducted to evaluate if miR-499 can potentially enhance the cisplatin sensitivity and therefore inhibit the proliferation of esophageal cancer (EC) cells. Flow cytometry and immunofluorescence microscopy assays were performed to evaluate whether miR-499 enhance the cisplatin sensitivity and the corresponding apoptosis in EC cells. Results: polβ was pinpointed as a target gene of miR-499. Additionally, we identified that miR-499 can enhance cisplatin's function of inhibiting proliferation and of promoting apoptosis in EC9706 and KYSE30 cell lines. Conclusions: We first investigated whether miR-499 modulates polβ, and observed the influence of miR-499 up-regulation on the sensitivity of EC cell lines to cisplatin treatment. Our study paves the way for more insightful understanding and application of chemotherapy in esophageal cancer in the future.
Studying the Psychological Profile of Patients with Laryngopharyngeal Reflux
Authors: Mesallam Tamer A. , Shoeib Rasha M. , Farahat Mohamed , Kaddah Fatma-Elzahraa A. , Malki Khalid H.
Published: July 2015

Background/Aims: Psychological factors have been claimed to play a role in the predisposition for laryngopharyngeal reflux (LPR) symptoms. The aims of this work were to study the relationship between psychological disorders and LPR and to investigate the effect of potential psychological disorders on patients' self-perception of reflux-related problems. Methods: Forty-two patients with symptoms suggestive of LPR were psychologically evaluated using the Social Readjustment Rating Scale, the Symptom Checklist-90 Revised, the Manifest Anxiety Scale of Taylor, the Minnesota Multiphasic Personality Inventory, and the Zung Self-Rating Depression Scale. Oropharyngeal 24-hour pH monitoring was used to diagnose LPR. LPR-related symptoms were assessed using the reflux symptom index (RSI) and the voice handicap index-10 (VHI-10). Patients were divided into groups based on psychiatric evaluation and pH results. Correlations between psychological profile characteristics and LPR-related parameters were also investigated. Results: No significant difference was found between the positive and negative LPR group for any of the assessed psychological disorders. Also, no significant difference was detected between the positive and negative psychological disorder groups regarding RSI, VHI-10, and pH results. Correlations between psychological profile parameters and LPR-related measures were also nonsignificant. Conclusion: It appears that there is no association between psychological disorders and LPR. The psychological background of the LPR patients had no influence on patients' self-perception of their reflux-related problems.
Clinical Characteristics of Transient Ischemic Attack Patients with Atrial Fibrillation: Analyses of a Multicenter Retrospective Study
Authors: Hama Yuka , Uehara Toshiyuki , Ohara Tomoyuki , Kimura Kazumi , Okada Yasushi , Hasegawa Yasuhiro , Tanahashi Norio , Suzuki Akifumi , Takagi Shigeharu , Nakagawara Jyoji , Arii Kazumasa , Nagahiro Shinji , Ogasawara Kuniaki , Nagao Takehiko , Uchiyama Shinichiro , Matsumoto Masayasu , Iihara Koji , Toyoda Kazunori , Minematsu Kazuo
Published: July 2015

Background: Atrial fibrillation (AF) is an important risk factor for transient ischemic attack (TIA). However, little is known about the characteristics of TIA patients with AF. This study investigated the characteristics of such patients, using data from a retrospective, observational, multicenter study. Methods: TIA patients admitted to 13 stroke centers in Japan within 7 days of onset between January 2008 and December 2009 were included. The present analyses compared baseline characteristics, clinical symptoms, findings from diffusion-weighted imaging (DWI), and clinical outcomes between patients with and without AF (AF and non-AF groups). Results: A total of 464 patients (292 men; mean age 68.5 ± 13.2 years) were registered. Of these, 79 patients (17%) had AF. Patients in the AF group were older (73.9 ± 9.1 vs. 67.4 ± 13.6 years, p < 0.001) and more likely to show disturbance of consciousness (13 vs. 6%, p = 0.046) and aphasia (9 vs. 3%, p = 0.007) than patients in the non-AF group. Although no difference in the overall DWI-positive rate was seen between the groups (28 vs. 20%, p = 0.102), a single lesion (23 vs. 10%, p < 0.001), a lesion ≥15 mm (11 vs. 4%, p = 0.006), and a single lesion ≥15 mm (11 vs. 2%, p < 0.001) on DWI were more frequent in the AF group. Multivariate logistic regression analysis identified increased age [odds ratio (OR) 1.04; 95% confidence interval (CI) 1.02-1.07] and DWI single lesion ≥15 mm (OR 5.67; 95% CI 1.92-16.7) as independently associated with the presence of AF. Conclusions: In this study, 17% of our TIA patients had AF. We found an association between the acute ischemic lesion pattern on DWI of a single lesion ≥15 mm and AF in TIA patients. These results might lead to a better diagnosis of TIA patients with AF.
Relationship between Nitrate-Induced Headache and Coronary Artery Lesion Complexity
Authors: Erkan Hakan , Kırış Gülhanım , Korkmaz Levent , Ağaç Mustafa Tarık , Çavuşoğlu İsmail Gökhan , Dursun İhsan , Yılmaz Ahmet Seyda , Aslan Ahmet Oğuz , Kırcı Dilek Cahide , Çelik Şükrü
Published: July 2015

Objective: The aim of the present study was to investigate the association between nitrate-induced headache (NIH) and the complexity of coronary artery lesions in patients with stable coronary artery disease (CAD). Subjects and Methods: Two hundred and seventy-five patients with anginal chest pain who underwent coronary angiography were enrolled in the present study. NIH was defined as the presence of headache due to nitrate treatment (isosorbide mononitrate 40 mg) after excluding confounding factors. Coronary artery lesion complexity was assessed by the SYNTAX score (SXscore) using a dedicated computer software system. Results: The mean SXscore was lower in the patients with NIH than in patients without NIH (7.3 ± 5.2 vs. 14.4 ± 8.5, respectively; p < 0.001). Additionally, patients with NIH had a lower rate of multivessel disease compared with those without NIH (the mean number of diseased vessels was 1.5 ± 0.7 and 2.0 ± 07, respectively; p < 0.001). In multivariate analysis, increasing age (p = 0.02) and headache (p = 0.001) were found to be independent determinants of SXscore. Conclusion: The present study demonstrated an independent inverse association between NIH and SXscore. The NIH could provide important predictive information about coronary artery lesion complexity in patients with stable CAD.
Glycogenic Hepatopathy: Thinking Outside the Box
Authors: Parmar Nishant , Atiq Muslim , Austin Lee , Miller Ross A. , Smyrk Thomas , Ahmed Kabir
Published: July 2015

Glycogenic hepatopathy (GH) remains underrecognized in adults as most clinicians mistake it for the more common hepatic abnormality associated with uncontrolled diabetes mellitus in this age group, non-alcoholic fatty liver disease. This is also complicated by the fact that both entities are indistinguishable on liver ultrasound. We herein describe a similar predicament in which a young adult female presented with bilateral upper quadrant abdominal pain, tender hepatomegaly, lactic acidosis and a >10-fold increase in liver enzymes, which worsened after the administration of high-dose steroids. Despite intravenous normal saline resuscitation, serum transaminitis persisted in a fluctuating manner. Ultimately, a liver biopsy confirmed GH. Biochemically, GH is driven by high amounts of both circulating glucose and insulin or by the administration of high-dose steroids. Improving glycemic control is the mainstay of treatment for GH. However, in our case, improvement in glycated hemoglobin of just 0.6% was enough to achieve symptomatic relief, supporting recent claims of the involvement of other identified factors in disease development.
Sex-Stratified Trends in Enrollment, Patient Characteristics, Treatment, and Outcomes Among Non–ST-Segment Elevation Acute Coronary Syndrome Patients
Authors: Kragholm Kristian , Halim Sharif A. , Yang Qinghong , Schulte Phillip J. , Hochman Judith S. , Melloni Chiara , Mahaffey Kenneth W. , Moliterno David J. , Harrington Robert A. , White Harvey D. , Armstrong Paul W. , Ohman E. Magnus , Van de Werf Frans , Tricoci Pierluigi , Alexander John H. , Giugliano Robert P. , Newby L. Kristin
Published: July 2015

Background—

Adequate representation by sex in trials allows generalizability of results. We examined representation of women in clinical trials during a 17-year period in which inclusion criteria were broadened and federal mandates for representativeness were launched.

Methods and Results—

Using mixed models, we studied sex-stratified temporal trends in enrollment, clinical characteristics, treatment, and outcomes among 76 148 non–ST-segment elevation acute coronary syndrome patients using patient-level data merged from 11 phase III trials conducted from 1994 to 2010. Overall, 33.3% of patients were women, which changed minimally over time. Women were consistently 4 to 5 years older than men (median age 68 [interquartile range 61–75] versus 64 [interquartile range 56–72] years) and more frequently had diabetes mellitus, hypertension, and heart failure; men more frequently had prior myocardial infarction and revascularization. GRACE risk scores increased over time for both sexes with the inclusion of older patients with more comorbidities. Use of percutaneous coronary intervention, in-hospital and discharge angiotensin-converting enzyme inhibitor/angiotensin II receptor blockers, β-blockers, and lipid-lowering drugs also increased among both sexes. Kaplan–Meier estimates of 6-month mortality declined from 7.0% [95% confidence interval 6.5%–7.6%] to 4.5% [95% confidence interval 4.0%–5.0%] among women and 6.3% [95% confidence interval 6.0%–6.7%] to 3.1% [95% confidence interval 2.9%–3.4%] among men during the 17-year period.

Conclusions—

The relative proportion of women in non–ST-segment elevation acute coronary syndrome trials changed minimally over time. Nevertheless, in parallel with men, use of evidence-based care and outcomes improved significantly over time among women.
Impact of Diabetes Mellitus on Hospitalization for Heart Failure, Cardiovascular Events, and Death
Authors: Cavender Matthew A. , Steg Ph. Gabriel , Smith Sidney C. , Eagle Kim , Ohman E. Magnus , Goto Shinya , Kuder Julia , Im Kyungah , Wilson Peter W.F. , Bhatt Deepak L.
Published: July 2015

Background—

Despite the known association of diabetes mellitus with cardiovascular events, there are few contemporary data on the long-term outcomes from international cohorts of patients with diabetes mellitus. We sought to describe cardiovascular outcomes at 4 years and to identify predictors of these events in patients with diabetes mellitus.

Methods and Results—

The Reduction of Atherothrombosis for Continued Health (REACH) registry is an international registry of patients at high risk of atherothrombosis or established atherothrombosis. Four-year event rates in patients with diabetes mellitus were determined with the corrected group prognosis method. Of the 45 227 patients in the REACH registry who had follow-up at 4 years, 43.6% (n=19 699) had diabetes mellitus at baseline. The overall risk and hazard ratio (HR) of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke were greater in patients with diabetes compared with patients without diabetes (16.5% versus 13.1%; adjusted HR, 1.27; 95% confidence interval [CI] 1.19–1.35). There was also an increase in both cardiovascular death (8.9% versus 6.0%; adjusted HR, 1.38; 95% CI, 1.26–1.52) and overall death (14.3% versus 9.9%; adjusted HR, 1.40; 95% CI, 1.30–1.51). Diabetes mellitus was associated with a 33% greater risk of hospitalization for heart failure (9.4% versus 5.9%; adjusted odds ratio, 1.33; 95% CI, 1.18–1.50). In patients with diabetes mellitus, heart failure at baseline was independently associated with cardiovascular death (adjusted HR, 2.45; 95% CI, 2.17–2.77;
P
<0.001) and hospitalization for heart failure (adjusted odds ratio, 4.72; 95% CI, 4.22–5.29;
P
<0.001).

Conclusions—

Diabetes mellitus substantially increases the risk of death, ischemic events, and heart failure. Patients with both diabetes mellitus and heart failure are at particularly elevated risk of cardiovascular death, highlighting the need for additional therapies in this high-risk population.
Safavid Cousins on the Verge of Extinction: Dynastic Centralization in Central Asia and the Bahrāmī Collateral Line (1517-1593)
Authors: Geevers Liesbeth
Published: July 2015

The Bahrāmī Safavids, a relatively unknown collateral branch of the Safavid dynasty, active in Iran from 1517 to 1593, played a crucial role in dynastic developments in Safavid Iran. This essay examines the dynastic developments of the Safavid rulers and their contemporaries to argue that they embarked on a process of dynastic centralization, presenting themselves increasingly as the only holder of dynastic power, at the expense of their male relatives. The persistence of the Bahrāmī branch illuminates how this process took shape in Iran and how dynastic developments among neighbouring Central Asian dynasties influenced the fate of the Safavid collaterals.
The Chronology of Roman Trade in the Indian Ocean from Augustus to Early Third Century ce
Authors: Cobb Matthew
Published: July 2015

The archaeological and numismatic evidence for Roman trade in the Indian Ocean from the Augustan annexation of Egypt up to the early third centuryceshows that the most intense period of contact and exchange was in the late first centuryce. The arguments presented here challenge two major positions, which assert either a peak during the Julio-Claudian period or a continuing intensity of contact until at least the late second centuryce.
Influence of prey species and concentration on egg production efficiency and hatching success in Acartia tonsa Dana (Copepoda, Calanoida)
Authors: Wendt I. , Thor P.
Published: July 2015

We measured ingestion rate (IR), egg production rate (EPR) and egg hatching success (EHS) at increasing prey concentrations and calculated egg production efficiency (EPE) and maintenance rate (MR) in the estuarine copepod Acartia tonsa fed three different algal diets. EPR and EHS were relatively more affected by prey species than by prey concentration. EPEs were constant among carbon concentrations (C) on a diet of Rhodomonas baltica (0.202 ± 0.055, mean ± SD) and Dunaliella tertiolecta (0.034 ± 0.015), but decreased significantly from 0.371 ± 0.062 (mean of two lowest prey concentrations) to 0.200 ± 0.019 at the highest concentration of Thalassiosira weissflogii. In general it seems that other requirements than C demand limit EPE and EHS in A. tonsa. The MR (IR when EPR = 0) was significantly higher on D. tertiolecta, which also yielded the lowest EPEs, and it seems that variations in maintenance requirements may have been instrumental in evoking EPE variations as well.
Agonistic interactions in the male fiddler crab Uca leptodactyla Rathbun, 1898 at varying densities
Authors: Santos L. C. , Alencar C. E. R. D. , Freire F. A. M. , Luchiari A. C.
Published: July 2015

In this study we tested the effect of population density on agonistic interactions in male Uca leptodactyla Rathbun, 1898. We recorded the crab’s behaviour in pairs or in groups of five animals composed of conspecifics and heterospecifics living in the same area (sympatric) and distinct areas (allopatric) of the mangrove forest. Allopatric conspecific crabs showed higher approaching and signalling than those in other conditions. The higher the crab density, the lower the interaction intensity between animals. Low-level agonistic signals were mainly displayed in high density (groups), while claw touch mainly occurred in pairs. Allopatric conspecifics showed the more intense agonistic interactions. Therefore, Uca seems to decrease energy investment in unnecessary fights against sympatric and conspecific crabs. Population density is a major factor driving agonistic behaviour mainly when conspecific animals are kept together. This may occur due to the increased competition for the same resources.
Descriptions of the postembryonic developmental stages of Hatschekia bifurcata Yamaguti & Yamasu, 1959 (Copepoda, Siphonostomatoida, Hatschekiidae)
Authors: Izawa Kunihiko
Published: July 2015

A series of descriptions of postembryonic developmental stages of Hatschekia bifurcata Yamaguti & Yamasu, 1959 is presented based on free-living larvae reared from eggs detached from ovigerous females recovered from the branchial lamellae of Aulacocephalus temmincki Bleeker, 1855, as well as on copepodids I-VI from A. temmincki and Diploprion bifasciatum Cuvier, 1828 (Pisces, Perciformes, Serranidae). The number of naupliar stages preceding the infective copepodid I is three in this species as in H. multibarbatae Izawa, 2015. A diagnostic feature of the species, a hook-like ventral process on the fourth antennular segment of the female, is regarded as an enlarged seta and was found to appear after copepodid V. A correction in the previously given setation of leg 2 and a complemental description of the antennule of the adult female are made. The male of this species is herein described for the first time. The sexes become distinct at copepodid III, and then growth curves of both sexes diverge stage by stage, as in H. multibarbatae. Aulacocephalus temmincki is reported as a new host species for H. bifurcata.
Morphological traits of gynodioecious Persicaria amphibia (Polygonaceae)
Authors: Moon Hye-Kyoung , Hong Suk-Pyo
Published: July 2015

Gynodioecy, as intermediate sexual system, involves modifications of floral structure from hermaphrodites to dioecy. We here present the morphological differences in the sexual type of flowers concerning the terrestrial Persicaria amphibia as a gynodioecious species. Hermaphroditic flowers are relatively larger than female ones, and they produce viable pollen grains, while female flowers produce no viable pollen as male-sterility but increase female fitness by exerted pistil. Although female flowers had aborted stamens, the anther development at the early stage was normal until the late stage which the anther locule of female flowers was collapsed without forming pollen-like structures. The pilate-glandular trichomes could be diagnostic characteristic of female individuals since this type of trichome occurs only in leaves, stems, and pedicels of female plants. Excepting for the trichome type, the variance of microstructures was not significant between hermaphroditic and female plants.
A new species of Anemopaegma (Bignonieae, Bignoniaceae) from the Atlantic Forest of Brazil
Authors: Leggieri Fabiana Firetti , DEMARCO DIEGO , LOHMANN LÚCIA G.
Published: July 2015

The Atlantic Forest of Brazil includes one of the highest species diversity and endemism in the planet, representing a priority for biodiversity conservation. A new species of Anemopaegma from the Atlantic Forest of Brazil is here described, illustrated and compared to its closest relatives. Anemopaegma nebulosum Firetti-Leggieri & L.G. Lohmann has been traditionally treated as a morph of Anemopaegma prostratum; however, additional morphological and anatomical studies indicated that A. nebulosum differs significantly from A. prostratum and is best treated as a separate species. More specifically, A. nebulosum is characterized by elliptic and coriaceous leaflets (vs. ovate to orbicular and membranaceous in A. prostratum), smaller leaflet blades (3.6–5.5 x 2.0–3.0 cm vs. 6.7–13.0 x 4.2–8.4 cm in A. prostratum), orbicular prophylls of the axillary buds (vs. no prophylls in A. prostratum), solitary flowers (vs. multi-flowered axillary racemes in A. prostratum) and a gibbous corolla (vs. infundibuliform corollas in A. prostratum). In addition, A. nebulosum differs from A. prostratum anatomically in having thicker leaflet blades composed of two to four layers of palisade parenchyma (vs. one to three layers in A. prostratum), and seven to eight layers in the spongy parenchyma (vs. six to eight layers in A. prostratum). A key for the identification of all species of Anemopaegma from the Atlantic Forest of Brazil is presented.
Systematics and morphology of Potamotrygon orbignyi (Castelnau, 1855) and allied forms (Chondrichthyes: Myliobatiformes: Potamotrygonidae)
Authors: SILVA JOÃO PAULO C. B. DA , CARVALHO MARCELO R. DE
Published: July 2015

The Neotropical freshwater stingray Potamotrygom orbignyi (Castelnau, 1855), and other similar "reticulated" species occurring in northern South American basins, were submitted to a thorough taxonomic analysis based on an extensive external and internal morphological study. The identity of P. orbignyi and the taxonomic status of the related nominal species Potamotrygon dumerilii (Castelnau, 1855), Potamotrygon reticulata (Günther, 1880), and Potamotrygon humerosa Garman, 1913, are defined. Taxonomic and morphological analyses revealed that P. reticulata and P. dumerilii fall within the range of variation found in P. orbignyi and were consequently treated as junior synonyms, corroborating previous works. The extensive variation in coloration observed in P. orbignyi could not be divided into consistent morphotypes; P. orbignyi is therefore a widespread species in the upper, mid and lower Amazonas basin, the Orinoco drainage, and in rivers of Suriname and the Guianas. Additionally, P. humerosa and Potamotrygon marinae Deynat, 2007 were found to present characters that support their validity, and are redescribed based on newly collected material. Potamotrygon humerosa occurs predominantly in the mid and lower Amazonas River and in lower reaches of many of its affluents, whereas P. marinae is known only from French Guiana and Suriname. Characters that proved valuable as diagnostic indicators, either in combination or as derived features, are primarily from coloration, dermal denticles and spines (morphology, development and distribution), meristic features (e.g. numbers of tooth rows, vertebrae and mesopterygial radials), morphometric proportions (e.g. snout length, tail width at base and length), and size at sexual maturity.
Labor Disputes and Job Flows
Authors: Fraisse Henri , Kramarz Francis , Prost Corinne
Published: July 2015

Using a data set of individual labor disputes brought to French courts over the years 1996 to 2003, the authors use variations in local conditions of the activity of the labor courts to assess the effect of dismissal costs on the labor market. First, the authors present a simple theoretical framework to explain the links between litigation costs, judicial outcomes, and firing costs. Second, they regress job flows on indicators of judicial outcomes, using an instrument, based on local shocks in the supply of lawyers. They find that when the numbers of lawyers increase, workers litigate more often, which should increase the firing costs for the firms. This increased filing rate causes a large decrease in employment fluctuations, especially for shrinking or exiting firms. The total effect on employment growth is slightly positive, and this result is more sensitive to the adopted specification.
NF-κB Enhances Androgen Receptor Expression through 5′-UTR Binding in Gingival Cells
Authors: Chang J.H. , Wang L.F. , Lu S.L. , Huang C.F. , Lu H.K.
Published: July 2015

Dihydropyridine-induced gingival overgrowth (DIGO) is a side effect observed in patients treated for hypertension. The disease is aggravated by inflammation. Nifedipine (Nif), a dihydropyridine, causes gingival overgrowth by increasing the expression of the androgen receptor (AR). Furthermore, the proinflammatory cytokine interleukin 1β (IL-1β) induces collagen α1(I) expression through the AR in DIGO fibroblasts. These observations prompted us to investigate whether and how nuclear factor kappa B (NF-κB) affects AR expression in DIGO. Therefore, gingival fibroblasts obtained from the tissues of patients with DIGO and healthy subjects were stimulated with IL-1β, Nif, or both. mRNA and protein expression was detected with real-time polymerase chain reaction and Western blotting. High correlation coefficients were observed for the mRNA expression of the AR, connective tissue growth factor, and collagen α1(I) induced by both drugs. Western blot analysis showed that IL-1β and Nif increased and activated NF-κB more in DIGO cells than in healthy cells. An electrophoretic mobility shift assay demonstrated that the promoter and 5′-untranslated regions (5′-UTRs) of the AR gene contains 3 binding sites for the NF-κB p65 subunit. A chromatin immunoprecipitation assay revealed that the NF-κB p65 subunit was associated with AR 5′-UTRs in gingival fibroblasts. A site-directed mutagenesis study indicated that a mutation of NF-κB binding sites reduced Nif- and IL-1β-induced AR promoter activities. Collectively, these data indicate that NF-κB is an essential transcriptional regulator of AR gene expression and thus plays a crucial role in collagen overproduction in DIGO fibroblasts.
Power over Profits
Authors: Dean Adam
Published: July 2015

Contemporary political economy debates tend to assume that an increase in productivity automatically leads to an equal increase in workers’ wages. This assumption shapes the way that many scholars think about economic globalization, as well as domestic policy reforms. This assumption is particularly widespread in the field of international political economy, where it is implicitly incorporated through the use of neoclassical economic models. Rather than explore the distributional struggle between capital and labor, these models use the assumption of full employment to predict that policies that increases worker productivity automatically leads to an equal increase in workers’ wages. In contrast, this article argues that the degree to which wages increase along with productivity depends on the domestic institutions that protect workers’ rights to act collectively. This article tests the relationship between worker productivity and wages by analyzing data from twenty-eight manufacturing industries, in 117 countries, from 1986 to 2002. The results demonstrate that the degree to which an increase in worker productivity leads to an increase in wages depends on a country’s level of protection for labor rights.
The China model withering? Institutional roots of China’s local developmentalism
Authors: Su Fubing , Tao Ran
Published: July 2015

China’s new development wave since the mid-1990s is distinguishable by its strong urbanism. Urban governments, particularly at municipal and county levels, rushed to build industrial parks. Urban landscape was also fundamentally transformed by their massive investments in infrastructures – both residential and commercial properties. How to explain local governments’ continuing drive for development? Why has this particular policy combination gained traction among local officials? We approach these questions by making a simple assumption about local governments as revenue maximisers. Their desires for more revenues are constrained by two institutional changes. Vertically, the central government recentralised the fiscal system, leaving local governments in fiscal shortages. Liberalisation and regional competition in the late 1990s further exacerbated their revenue imperative. The land regime provided the final institutional link that enabled local officials to leverage urban infrastructure and real estate for industrial expansion. This study can shed some light on the ongoing debate about China’s development model in the urban literature.
China Rising
Authors: Curado Marcelo
Published: July 2015

China’s economic rise has caused a radical change in the operating conditions of the capitalist system and opened a wide range of opportunities and challenges for Brazil’s development. The Brazilian productive structure is going through great changes, key among them being the loss of importance of the manufacturing industry in job creation and in total GDP, and the efforts of Brazilian capitalists to promote investment and innovation have fallen short. The latter is a key element for an understanding of Brazilian industry’s weak participation in the highly competitive international scene. These opportunities and challenges can only be adequately addressed by the maintenance and expansion of the planning efforts of the state.

A ascensão econômica da China tem causado mudança radical nas condições de fun-cionamento do sistema capitalista e criou um vasto espectro de oportunidades e desafios ao desenvolvimento do Brasil. A estrutura produtiva brasileira vem passando por grandes transformações. Entre elas, uma das mais sérias tem sido a perda na capacidade da indústria manufatureira de gerar empregos e a queda de sua participação no PIB. Demais, nota-se que os esforços de capitalistas brasileiros para promover investimento e inovação têm sido pífios. Esse último problema constitui elemento-chave para compreender-se a participação fraca da indústria brasileira em um cenário international extremamente competitivo. As oportunidades e desafios mencionados só podem ser adequadamente tratados por meio da manutenção e expansão do planejamento estatal.