bluuebunny/crossref_metadata_2025 huggingface dataset:
IL-18 mediates proapoptotic signaling in renal tubular cells through a Fas ligand-dependent mechanism
Authors: Zhang Hongji , Hile Karen L. , Asanuma Hiroshi , Vanderbrink Brian , Franke Ethan I. , Campbell Matthew T. , Meldrum Kirstan K.
Published: April 2011

Renal tubular cell apoptosis is a significant component of obstruction-induced renal injury, and it results in a progressive loss in renal parenchymal mass during renal obstruction. Although IL-18 is an important mediator of inflammatory renal disease and renal fibrosis, its role in obstruction-induced renal tubular cell apoptosis remains unclear. To study this, male C57BL6 wild-type mice and C57BL6 mice transgenic for human IL-18-binding protein (IL-18BP Tg) were subjected to renal obstruction vs. sham operation. The kidneys were harvested after 1 or 2 wk and analyzed for IL-18 production, apoptosis, caspase activity, and Fas/Fas Ligand (FasL) expression. HK-2 cells were similarly analyzed for apoptosis and proapoptotic signaling following 3 days of direct exposure to IL-18 vs. control media. Renal obstruction induced a significant increase in IL-18 production, renal tubular cell apoptosis, caspase activation, and FasL expression. IL-18 neutralization, on the other hand, significantly reduced obstruction-induced apoptosis, caspase-8 and caspase-3 activity, and FasL expression. In vitro experiments similarly demonstrate that IL-18 stimulation induces apoptosis, FasL expression, and increases active caspase-8 and caspase-3 expression in a dose-dependent fashion. siRNA knockdown of FasL gene expression, however, significantly reduced IL-18-induced apoptosis. This study reveals that IL-18 is a significant mediator of obstruction-induced tubular cell apoptosis, and it demonstrates that IL-18 stimulates proapoptotic signaling through a FasL-dependent mechanism.
Induction of hyperglycemia in adult intrauterine growth-restricted rats: effects on renal function
Authors: Lim Kyungjoon , Lombardo Paul , Schneider-Kolsky Michal , Hilliard Lucinda , Denton Kate M. , Black M. Jane
Published: April 2011

Intrauterine growth restriction (IUGR) leads to a reduction in nephron endowment at birth and is linked to renal dysfunction in adulthood. The aim of the present study was to determine whether kidneys of IUGR rat offspring are more vulnerable to a secondary insult of hyperglycemia. IUGR was induced in Wistar-Kyoto rats by maternal protein restriction. At 24 wk of age, diabetes was induced in male IUGR and non-IUGR offspring by streptozotocin injection; insulin was injected daily to maintain blood glucose levels at either a mild (7–10 mmol/l; n=8/group) or a moderate (10–15 mmol/l; n=8/group) level. At 32 wk of age, renal function was assessed using ultrasound and [3H]inulin and [14C]para-aminohippurate clearance techniques. Conscious mean arterial blood pressure and heart rate were unchanged in IUGR offspring. Relative kidney length was increased significantly in IUGR offspring, and renal function was altered significantly; of importance, there was a significant increase in filtration fraction, indicative of glomerular hyperfiltration. Induction of hyperglycemia led to marked impairment of renal function. However, the response to hyperglycemia was not different between IUGR and non-IUGR offspring. Maintaining blood glucose levels at a mild hyperglycemic level led to marked improvement in all measures of renal function in IUGR and non-IUGR offspring. In conclusion, while the IUGR offspring showed evidence of hyperfiltration, the response to hyperglycemia was similar in IUGR and non-IUGR kidneys in adulthood. Importantly, maintaining blood glucose levels at a mild hyperglycemic level markedly attenuated the renal dysfunction associated with diabetes, even in IUGR offspring.
HOXC9 Links Cell-Cycle Exit and Neuronal Differentiation and Is a Prognostic Marker in Neuroblastoma
Authors: Mao Ling , Ding Jane , Zha Yunhong , Yang Liqun , McCarthy Brian A. , King William , Cui Hongjuan , Ding Han-Fei
Published: April 2011

Differentiation status in neuroblastoma strongly affects clinical outcomes and inducing differentiation is a treatment strategy in this disease. However, the molecular mechanisms that control neuroblastoma differentiation are not well understood. Here, we show that high-level HOXC9 expression is associated with neuroblastoma differentiation and is prognostic for better survival in neuroblastoma patients. HOXC9 induces growth arrest and neuronal differentiation in neuroblastoma cells by directly targeting both cell-cycle–promoting and neuronal differentiation genes. HOXC9 expression is upregulated by retinoic acid (RA), and knockdown of HOXC9 expression confers resistance to RA-induced growth arrest and differentiation. Moreover, HOXC9 expression is epigenetically silenced in RA-resistant neuroblastoma cells, and forced HOXC9 expression is sufficient to inhibit their proliferation and tumorigenecity. These findings identified HOXC9 as a key regulator of neuroblastoma differentiation and suggested a therapeutic strategy for RA-resistant neuroblastomas through epigenetic activation of HOXC9 expression. Cancer Res; 71(12); 4314–24. ©2011 AACR.
Global Hypomethylation Identifies Loci Targeted for Hypermethylation in Head and Neck Cancer
Authors: Poage Graham M. , Houseman E. Andres , Christensen Brock C. , Butler Rondi A. , Avissar-Whiting Michele , McClean Michael D. , Waterboer Tim , Pawlita Michael , Marsit Carmen J. , Kelsey Karl T.
Published: April 2011

Purpose: The human epigenome is profoundly altered in cancers, with a characteristic loss of methylation in repetitive regions and concomitant accumulation of gene promoter methylation. The degree to which these processes are coordinated is unclear so we investigated both in head and neck squamous cell carcinomas.

Experimental Design: Global methylation was measured using the luminometric methylation assay (LUMA) and pyrosequencing of LINE-1Hs and AluYb8 repetitive elements in a series of 138 tumors. We also measured methylation of more than 27,000 CpG loci with the Illumina HumanMethylation27 Microarray (n = 91).

Results: LINE-1 methylation was significantly associated with LUMA and Infinium loci methylation (Spearman's ρ = 0.52/ρ = 0.56, both P < 0.001) but not that of AluYb8. Methylation of LINE-1, AluYb8, and Infinium loci differed by tumor site (each Kruskal–Wallis, P < 0.05). Also, LINE-1 and LUMA methylation were associated with HPV16 E6 serology (each Mann–Whitney, P < 0.05). Comparing LINE-1 methylation to gene-associated methylation, we identified a distinct subset of CpG loci with significant hypermethylation associated with LINE-1 hypomethylation. An investigation of sequence features for these CpG loci revealed that they were significantly less likely to reside in repetitive elements (Gene Set Enrichment Analysis, P < 0.02), enriched in CpG islands (P < 0.001) and were proximal to transcription factor–binding sites (P < 0.05). We validated the top CpG loci that had significant hypermethylation associated with LINE-1 hypomethylation (at EVI2A, IFRD1, KLHL6, and PTPRCAP) by pyrosequencing independent tumors.

Conclusions: These data indicate that global hypomethylation and gene-specific methylation processes are associated in a sequence-dependent manner, and that clinical characteristics and exposures leading to HNSCC may be influencing these processes. Clin Cancer Res; 17(11); 3579–89. ©2011 AACR.
Poultry Genome Sequences: Progress and Outstanding Challenges
Authors: Dodgson J.B. , Delany M.E. , Cheng H.H.
Published: April 2011

The first build of the chicken genome sequence appeared in March, 2004 – the first genome sequence of any animal agriculture species. That sequence was done primarily by whole genome shotgun Sanger sequencing, along with the use of an extensive BAC contig-based physical map to assemble the sequence contigs and scaffolds and align them to the known chicken chromosomes and linkage groups. Subsequent sequencing and mapping efforts have improved upon that first build, and efforts continue in search of missing and/or unassembled sequence, primarily on the smaller microchromosomes and the sex chromosomes. In the past year, a draft turkey genome sequence of similar quality has been obtained at a much lower cost primarily due to the development of ‘next-generation’ sequencing techniques. However, assembly and alignment of the sequence contigs and scaffolds still depended on a detailed BAC contig map of the turkey genome that also utilized comparison to the existing chicken sequence. These 2 land fowl (Galliformes) genomes show a remarkable level of similarity, despite an estimated 30–40 million years of separate evolution since their last common ancestor. Among the advantages offered by these sequences are routine re-sequencing of commercial and research lines to identify the genetic correlates of phenotypic change (for example, selective sweeps), a much improved understanding of poultry diversity and linkage disequilibrium, and access to high-density SNP typing and association analysis, detailed transcriptomic and proteomic studies, and the use of genome-wide marker- assisted selection to enhance genetic gain in commercial stocks.
Integrated Cytogenetic and High-Resolution Array CGH Analysis of Genomic Alterations Associated with MYCN Amplification
Authors: Pandita A. , Bayani J. , Paderova J. , Marrano P. , Graham C. , Barrett M. , Prasad M. , Zielenska M. , Squire J.A.
Published: April 2011

Amplification of oncogenes and closely linked flanking genes is common in some types of cancer and can be associated with complex chromosome rearrangements and/or co-amplification of non-syntenic chromosomal regions. To better understand the etiology and structural complexity of focal MYCN amplicons in human neuronal cancer, we investigated the precise chromosomal locations of high copy number genomic regions in MYCN amplified cell lines. An integrated cytogenetic map of the MYCN amplicon was created using high-resolution array CGH, spectral karyotyping (SKY), multi-color banding (mBAND), and fluorescence in situ hybridization (FISH) in 4 human neuronal tumor cell lines. The evidence of complex intra- and inter-chromosomal events, providing clues concerning the nature of the genomic mechanisms that contributed to the process of MYCN amplification, was observed. The presence of multiple co-amplified syntenic or non-syntenic sequences in the MYCN amplicon is quite intriguing. MYCN is usually centrally located in the amplicon; however, the structure and complexity of the amplicons were highly variable. It is noteworthy that clusters of unstable repetitive regions characterized by CNV sequences were present throughout the regions encompassed by MYCN gene amplification, and these sequences could provide a mechanism to destabilize this region of the genome. Complex structural rearrangements involving genomic losses and gains in the 2p24 region lead to MYCN amplification and that these rearrangements can trigger amplification events.
Language Specificity in Speech Perception: Perception of Mandarin Tones by Native and Nonnative Listeners
Authors: Huang Tsan , Johnson Keith
Published: April 2011

The results reported in this paper indicate that native speakers of Mandarin Chinese rate the perceptual similarities among the lexical tones of Mandarin differently than do native speakers of American English. Mandarin listeners were sensitive to tone contour while English listeners attended to pitch levels. Chinese listeners also rated tones that are neutralized by phonological tone sandhi rules in Mandarin as more similar to each other than did English speakers – indicating a role of phonology in determining perceptual salience. In two further experiments, we found that some of these differences were eliminated when the listening task focused listeners’ attention on the auditory properties of the stimuli, but, interestingly, a degree of language specificity remained even in the most purely psychophysical listening tasks with speech stimuli.
Effect of Bardoxolone Methyl on Kidney Function in Patients with T2D and Stage 3b–4 CKD
Authors: Pergola Pablo E. , Krauth Melissa , Huff J. Warren , Ferguson Deborah A. , Ruiz Stacey , Meyer Colin J. , Warnock David G.
Published: April 2011

Background/Aims: Bardoxolone methyl, a novel synthetic triterpenoid, induces Nrf2, a transcription factor known to play a key role in decreasing oxidative stress and the production of pro-inflammatory molecules. Methods: This exploratory multi-center, open-label study assessed the clinical activity and safety of bardoxolone methyl in 20 patients with moderate to severe chronic kidney disease and type 2 diabetes. Patients received 25 mg of bardoxolone methyl daily for 28 days, followed by 75 mg daily for another 28 days. Results: The study achieved its primary efficacy endpoint, as demonstrated by a significant increase from baseline in estimated glomerular filtration rate (eGFR) of 7.2 ml/min/1.73 m2 (p < 0.001). Improvements were seen in approximately 90% of patients and showed a dose- and time-dependent increase in eGFR. The eGFR change paralleled a significant reduction in serum creatinine (–0.3 mg/dl) and blood urea nitrogen (–4.9 mg/dl), along with an increase in creatinine clearance (+14.6 ml/min/1.73 m2), without a change in the 24-hour creatinine excretion rate. Markers of vascular injury and inflammation were improved by treatment with bardoxolone. No life-threatening adverse events or drug-related serious adverse events were reported. Conclusions: The results describe an apparent increase in kidney function following relatively short-term treatment with bardoxolone methyl, a promising new agent that warrants placebo-controlled studies to define its long-term effects on renal function.
Efficacy and Safety of Rituximab Second-Line Therapy for Membranous Nephropathy: A Prospective, Matched-Cohort Study
Authors: Cravedi Paolo , Sghirlanzoni Maria Chiara , Marasà Maddalena , Salerno Alessandra , Remuzzi Giuseppe , Ruggenenti Piero
Published: April 2011

Background/Aims: First-line immunosuppression with the B-cell depleting antibody rituximab reduced proteinuria and induced remission of the disease in patients with nephrotic syndrome (NS) secondary to idiopathic membranous nephropathy (IMN). Here we evaluated whether rituximab is equally effective in patients who failed to respond to previous immunosuppressive treatment. Methods: This academic, matched-cohort study, compared 2-year outcomes of 11 consecutive IMN patients who received second-line rituximab therapy for NS persisting or relapsing after previous treatment with steroids alone or combined with alkylating agents, cyclosporine, or immunoglobulin G, with those of 11 age- (±5 years), gender- and proteinuria- (±1 g/24h) matched reference patients given first-line rituximab therapy. Results: Patients’ and reference patients’ baseline characteristics were similar. Compared to baseline, 24-hour proteinuria similarly declined at 1 and 2 years post-rituximab (by 50.5 ± 25.1% and 60.9 ± 17.4% in patients and by 52.7 ± 31.5% and 69.4 ± 40.4% in reference patients, respectively; p < 0.01 for all comparisons vs. baseline). 8 patients and 7 reference patients achieved full (3 vs. 2) or partial (5 per cohort) proteinuria remission. Hypoalbuminemia and hyperlipidemia normalized in both groups. Self-limited infusion-related reactions occurred in 1 subject per cohort. Conclusion: Rituximab reduced proteinuria in IMN patients with no or only transientresponse to unselective immunosuppression as effectively and safely as in patients without previous immunosuppression.
Suppressors of Cytokine Signaling (SOCS) Proteins and JAK/STAT Pathways
Authors: Tamiya Taiga , Kashiwagi Ikko , Takahashi Reiko , Yasukawa Hideo , Yoshimura Akihiko
Published: April 2011

Various cytokines are involved in the regulation of the immune system and inflammation. Dysregulation of cytokine signaling can cause a variety of diseases, including allergy, autoimmune diseases, inflammation, and cancer. Most cytokines use the so-called janus kinase/signal transducer and activator of transcription pathway, and this pathway is negatively regulated by suppressors of cytokine signaling (SOCS) proteins. SOCS proteins bind to janus kinase and to certain cytokine receptors and signaling molecules, thereby suppressing further signaling events. Studies have shown that SOCS proteins are key physiological regulators of inflammation. Recent studies have also demonstrated that SOCS1 and SOCS3 are important regulators of adaptive immunity.
Grounding Systematic Syncretism in Learning
Authors: Pertsova Katya
Published: April 2011

It is commonly assumed that patterns of syncretism in inflectional paradigms are restricted in some way. In this article, I show how such restrictions can reflect cognitive constraints on language learning. Namely, I construct a learning algorithm that is biased toward certain types of affix distributions in paradigms, thereby rendering them systematic. In developing this algorithm, I rely on the traditional notions of underspecification and blocking, but recast them in terms of learners' biases toward generalization strategies based on cross-situational intersections and default reasoning. This algorithm allows us to test claims about systematicity of syncretism using typological data and language acquisition studies. In the last part of the article, I present a crosslinguistic survey of verbal agreement paradigms that supports the algorithm's predictions.
Do We Observe Aerosol Impacts on DSDs in Strongly Forced Tropical Thunderstorms?
Authors: May P. T. , Bringi V. N. , Thurai M.
Published: April 2011

Rain drop size distributions retrieved from polarimetric radar measurements over regularly occurring thunderstorms over the islands north of Darwin, Australia, are used to test if aerosol contributions to the probability distributions of the drop size distribution parameters (median volume diameter and normalized intercept parameter) are detectable. The observations reported herein are such that differences in cloud properties arising from thermodynamic differences are minimized but even so may be a factor. However, there is a clear signature that high aerosol concentrations are correlated with smaller number concentrations and larger drops. This may be associated with enhanced ice multiplication processes for low aerosol concentration storms or other processes such as invigoration of the updrafts.
The Diurnal Behavior of Evaporative Fraction in the Soil–Vegetation–Atmospheric Boundary Layer Continuum
Authors: Gentine Pierre , Entekhabi Dara , Polcher Jan
Published: April 2011

The components of the land surface energy balance respond to periodic incoming radiation forcing with different amplitude and phase characteristics. Evaporative fraction (EF), the ratio of latent heat to available energy at the land surface, supposedly isolates surface control (soil moisture and vegetation) from radiation and turbulent factors. EF is thus supposed to be a diagnostic of the surface energy balance that is constant or self-preserved during daytime. If this holds, EF can be an effective way to estimate surface characteristics from temperature and energy flux measurements. Evidence for EF diurnal self-preservation is based on limited-duration field measurements. The daytime EF self-preservation using both long-term measurements and a model of the soil–vegetation–atmosphere continuum is reexamined here. It is demonstrated that EF is rarely constant and that its temporal power spectrum is wide; thus emphasizing the role of all diurnal frequencies associated with reduced predictability in its daylight response. Oppositely, surface turbulent heat fluxes are characterized by a strong response to the principal daily frequencies (daily and semi-daily) of the solar radiative forcing. It is shown that the phase lag and bias between the turbulent flux components of the surface energy balance are key to the shape of the daytime EF. Therefore, an understanding of the physical factors that affect the phase lag and bias in the response of the components of the surface energy balance to periodic radiative forcing is needed. A linearized model of the soil–vegetation–atmosphere continuum is used that can be solved in terms of harmonics to explore the physical factors that determine the phase characteristics. The dependency of these phase and offsets on environmental parameters—friction velocity, water availability, solar radiation intensity, relative humidity, and boundary layer entrainment—is then analyzed using the model that solves the dynamics of subsurface and atmospheric boundary layer temperatures and heat fluxes in a continuum. Additionally, the asymptotical diurnal lower limit of EF is derived as a function of these surface parameters and shown to be an important indicator of the self-preservation value when the conditions (also identified) for such behavior are present.
Cilostazol in Diabetic Neuropathy
Authors: Papanas N. , Maltezos E.
Published: April 2011

Peripheral neuropathy remains a major chronic complication of diabetes mellitus. Its pathogenesis mainly involves chronic glucose toxicity and nerve ischemia. Preclinical studies have shown that cilostazol, a reversible selective inhibitor of phosphodiesterase-3A with antiplatelet, antithrombotic, and vasodilatory properties, exerts beneficial effects on nerve function in experimental diabetes. Clinical data, however, is sparse. Two recent randomized placebo-controlled clinical trials showed that cilostazol did not improve diabetic neuropathy in humans. Hence, more data is needed to confirm or refute the poor clinical efficacy of cilostazol. Importantly, future studies should include larger patient series, provide longer follow-up data, and employ more accurate diagnostic tools.
The Right to Vision
Authors: Davis Diane E. , Hatuka Tali
Published: April 2011

Building on Henri Lefebvre’s work on the role of imagination in crafting socially just urban conditions and “rights to the city,” this paper asks whether new ideas and urban practices can be produced through the use of experimental visioning techniques. Using empirical evidence drawn from an ideas competition for Jerusalem, one of the world’s most intractable conflict cities, the paper considers the extent to which the global call to create alternative visions for a just, peaceful, and sustainable Jerusalem resulted in new strategies considered fundamentally different from those routinely deployed in conventional planning practice, how and why.
A Population-Based Study of Job Stress in Mexican Americans, non-Hispanic Blacks, and non-Hispanic Whites
Authors: Perez Norma , Franzini Luisa , Freeman Daniel H. , Ju Hyunsu , Peek Kristen
Published: April 2011

There is little known about the association between socioeconomic status and job stress in Mexican Americans. To address this issue, data were originated on a community level using personal interviews from working Mexican Americans using a multistage probability sample. In this study we described the population’s sociodemographic characteristics, health conditions, and job stress measures in Mexican Americans, non-Hispanic Whites, and non-Hispanic Blacks. Regression models were used to examine the associations of sociodemographic characteristics and health conditions for each job stress measure among 937 individuals. Our results indicate an association between low socioeconomic status and the perception of less job control, less job security, and less social support. Mexican Americans demonstrated more job security and social support in comparison to non-Hispanic Whites of similar socioeconomic status. We were able to define potential factors that may contribute to an individual’s perception of job stress.
Depressive Symptoms, Social Support, and Walking Among Hispanic Older Adults
Authors: Perrino Tatiana , Brown Scott C. , Huang Shi , Brown C. Hendricks , Gómez Gianna Pérez , Pantin Hilda , Szapocznik José
Published: April 2011

Objectives: Depressive symptoms and physical inactivity are health risks among minority older adults. This study examined whether social support moderated the relationship of depressive symptoms to walking behavior among 217 community-dwelling, Hispanic older adults. Method: Cross-sectional analyses were used to test whether different forms of social support interacted with depressive symptoms to affect both likelihood and amount of walking. Results: Analyses showed a significant interaction between depressive symptoms and instrumental support related to the likelihood of walking and a marginally significant interaction between depressive symptoms and instrumental social support related to the amount of walking. Depressive symptoms were associated with a lower likelihood and lower amount of walking among participants receiving high levels of instrumental social support (e.g., help with chores) but not low instrumental support. Emotional and informational support did not moderate the depression to walking relationship. Conclusion: Receiving too much instrumental support was related to sedentary behavior among depressed older adults.
Causes and prevention of herb-induced aconite poisonings in Asia
Authors: Chan Thomas YK
Published: April 2011

The recent reports from Hong Kong, Taiwan, China and Korea were reviewed to determine the causes and prospects for prevention of herb-induced aconite poisonings. The contributory factors included overdose (use of greater than the recommended doses), faulty processing (after harvest and during decoction), use of tincture (herbal medicinal wine), use of crude aconite roots (for preparing decoction, proprietary medicines and tincture), lack of standardisation in processing of aconite roots and preparation of tincture and proprietary medicines, unsupervised use of aconite roots and contamination or mix-up with aconite roots. As tincture (herbal medicinal wine) made from aconite roots contains a much larger amount of Aconitum alkaloids, the public should be strongly discouraged from making their own and taking it by mouth. Aconite roots should only be used after post-harvest processing and proper decoction. The public should be educated on the hazards from unsupervised use and improper decoction of processed aconite roots. There should be regular publicity measures to promote awareness among the herbalists and to publicise the risk of serious cardiotoxicity if the recommended doses of processed aconite roots are exceeded. The processing of aconite roots and their proprietary preparations should be standardised. Quality control of processed aconite roots and their proprietary preparations should be strengthened. National reporting or monitoring systems can be used to identify the causes of aconite poisonings and assess the impact of preventive measures.
SENATE BARON: A Simulation of Politics in the U.S. Senate, 1933-1942
Authors: Moser John E.
Published: April 2011

SENATE BARON is an educational simulation in which each participant takes on the role of a U.S. Senator during the administration of Franklin D. Roosevelt. As few as 12 and as many as 96 participants may participate in this. Players strive to gain influence by promoting legislation that they support and by blocking legislation that they oppose. The goal of the exercise is to illustrate the political climate of the 1930s, and the difficulties involved in building coalitions for and against various proposals. Facilitators may also wish to teach about the rhetorical strategies employed by the senators of the time through use of the optional Debate Phase.
Methodological, Theoretical, Infrastructural, and Design Issues in Conducting Good Outcome Studies
Authors: Kelly Michael P. , Moore Tessa A.
Published: April 2011

This article outlines a set of methodological, theoretical, and other issues relating to the conduct of good outcome studies. The article begins by considering the contribution of evidence-based medicine to the methodology of outcome research. The lessons which can be applied in outcome studies in nonmedical settings are described. The article then examines the role of causal pathways between interventions and outcomes and especially the importance of delineating them in advance of undertaking investigations. The development of designs based on randomized controlled trials (RCTs) with fully articulated causal pathways is described. Ways of supplementing RCTs with methods to highlight elements in the causal pathway in outcome studies are indicated. The importance of adhering to best practice in reporting and analysis is also noted.
When citizen photojournalism sets the news agenda: Neda Agha Soltan as a Web 2.0 icon of post-election unrest in Iran
Authors: Mortensen Mette
Published: April 2011

The article discusses the current rise of citizen photojournalism, which has received little scholarly scrutiny. Drawing on a case study of the mobile telephone footage of the Iranian woman Neda Agha Soltan, who was killed during a demonstration in Iran in June 2009, the article investigates the ethical dilemmas of the Western news media’s eager use of citizen photojournalism as a unique and headline-grabbing source. While these images may grant us insight into areas of tension, to which the media has no other access, amateur footage challenges the ethical standards of conventional journalism with its fragmentary and subjective format, not to mention the difficulties involved in tracking a clip’s author and origin. Even though the news media indisputably play an essential role as a platform for editorial selection and communication of citizen photojournalism, this article points to a general lack of editorial procedures for accommodating these new sources.
Nasal obstruction as a drug side effect
Authors: Cingi Cemal , Ozdoganoglu Tunis , Songu Murat
Published: April 2011

Nasal obstruction is a common symptom of various diseases, allergies, and structural deformities and a ‘stuffy nose’ is one of the most common reasons that patients seek a physician’s aid. Drugs that affect the autonomic nervous system are also expected to have a vasoactive effect on the nose. Nasal obstruction in the absence of infectious rhinitis or allergic symptoms may be due to drug use. With the chronic use of a medication, nasal obstruction can change over time and can be underestimated. Very little is known about this topic and very few publications to date solely devoted to drug-induced rhinitis. To prevent complications, obvious nasal obstruction due to drug intake should be treated with appropriate medication(s) or surgical intervention(s).
Granulocyte-CSF induced inflammation-associated cardiac thrombosis in iron loading mouse heart and can be attenuated by statin therapy
Authors: Lian Wei S , Lin Heng , Cheng Winston TK , Kikuchi Tateki , Cheng Ching F
Published: April 2011

Background

Granulocyte colony-stimulating factor (G-CSF), a hematopoietic cytokine, was recently used to treat patients of acute myocardial infarction with beneficial effect. However, controversy exists as some patients developed re-stenosis and worsened condition post G-CSF delivery. This study presents a new disease model to study G-CSF induced cardiac thrombosis and delineate its possible mechanism. We used iron loading to mimic condition of chronic cardiac dysfunction and apply G-CSF to mice to test our hypothesis.

Methods and Results

Eleven out of fifteen iron and G-CSF treated mice (I+G) showed thrombi formation in the left ventricular chamber with impaired cardiac function. Histological analysis revealed endothelial fibrosis, increased macrophage infiltration and tissue factor expression in the I+G mice hearts. Simvastatin treatment to I+G mice attenuated their cardiac apoptosis, iron deposition, and abrogated thrombus formation by attenuating systemic inflammation and leukocytosis, which was likely due to the activation of pAKT activation. However, thrombosis in I+G mice could not be suppressed by platelet receptor inhibitor, tirofiban.

Conclusions

Our disease model demonstrated that G-CSF induces cardiac thrombosis through an inflammation-thrombosis interaction and this can be attenuated via statin therapy. Present study provides a mechanism and potential therapy for G-CSF induced cardiac thrombosis.
Primary extrahepatic alveolar echinococcosis of the lumbar spine and the psoas muscle
Authors: Nell Manuel , Burgkart Rainer H , Gradl Guntmar , von Eisenhart-Rothe Rüdiger , Schaeffeler Christoph , Trappe Dennis , da Costa Clarissa Prazeres , Gradinger Reiner , Kirchhoff Chlodwig
Published: April 2011

Alveolar echinococcosis (AE) of human being caused by Echinococcus multilocularis is a rare but important zoonosis especially in tempered zones of middle Europe and Northern America with endemic character in many countries. Due to the long incubation period, various clinical manifestations, critical prognosis, and outcome AE presents a serious and severe disease. The primary focus of infection is usually the liver. Although secondary affection of visceral organs is possible extrahepatic AE is highly uncommon. Moreover, the involvement of bone and muscle presents with an even lower incidence. In the literature numerous cases on hepatic AE have been reported. However, extrahepatic AE involving bones and/or muscles was described very rarely. We report a case of an 80-year-old man with primary extrahepatic alveolar Echinococcosis of the lumbar spine and the psoas muscle. The etiology, diagnosis, differential diagnoses, treatment options and outcome of this rare disease are discussed in context with the current literature.
Regulation of pregnancy-associated plasma protein A2 (PAPPA2) in a human placental trophoblast cell line (BeWo)
Authors: Wagner Pamela K , Otomo Aki , Christians Julian K
Published: April 2011

Background

Pregnancy-associated plasma protein A2 (PAPPA2) is an insulin-like growth factor-binding protein (IGFBP) protease expressed at high levels in the placenta and upregulated in pregnancies complicated by preeclampsia and HELLP (Hemolytic anemia, Elevated Liver enzymes, and Low Platelet count) syndrome. However, it is unclear whether elevated PAPPA2 expression causes abnormal placental development, or whether upregulation compensates for placental pathology. In the present study, we investigate whether PAPPA2 expression is affected by hypoxia, oxidative stress, syncytialization factors or substances known to affect the expression of PAPPA2's paralogue, PAPPA.

Methods

BeWo cells, a model of placental trophoblasts, were treated with one of the following: hypoxia (2% O2), oxidative stress (20 microM hydrogen peroxide), forskolin (10 microM and 100 microM), TGF-beta (10 and 50 ng/mL), TNF-alpha (100 ng/mL), IL-1beta (100 ng/mL) or PGE2 (1 microM). We used quantitative RT-PCR (qRT-PCR) to quantify the mRNA levels of PAPPA2, as well as those of PAPPA and ADAM12 since these proteases have similar substrates and are also highly expressed in the placenta. Where we observed significant effects on PAPPA2 mRNA levels, we tested for effects at the protein level using an in-cell Western assay.

Results

Hypoxia, but not oxidative stress, caused a 47-fold increase in PAPPA2 mRNA expression, while TNF-alpha resulted in a 6-fold increase, and both of these effects were confirmed at the protein level. PGE2 resulted in a 14-fold upregulation of PAPPA2 mRNA but this was not reflected at the protein level. Forskolin, TGF-beta and IL-1beta had no significant effect on PAPPA2 mRNA expression. We observed no effects of any treatment on PAPPA or ADAM12 expression.

Conclusion

Our study demonstrates that factors previously known to be highly expressed in preeclamptic placentae (PGE2 and TNF-alpha), contribute to the upregulation of PAPPA2. Hypoxia, known to occur in preeclamptic placentae, also increased PAPPA2 expression. These results are consistent with the hypothesis that PAPPA2 is upregulated as a consequence of placental pathology, rather than elevated PAPPA2 levels being a cause of preeclampsia.
The alkylphospholipid, perifosine, radiosensitizes prostate cancer cells both in vitro and in vivo
Authors: Gao Yuanhong , Ishiyama Hiromichi , Sun Mianen , Brinkman Kathryn L , Wang Xiaozhen , Zhu Julie , Mai Weiyuan , Huang Ying , Floryk Daniel , Ittmann Michael , Thompson Timothy C , Butler E Brian , Xu Bo , Teh Bin S
Published: April 2011

Background

Perifosine is a membrane-targeted alkylphospholipid developed to inhibit the PI3K/Akt pathway and has been suggested as a favorable candidate for combined use with radiotherapy. In this study, we investigated the effect of the combined treatment of perifosine and radiation (CTPR) on prostate cancer cells in vitro and on prostate cancer xenografts in vivo.

Methods

Human prostate cancer cell line, CWR22RV1, was treated with perifosine, radiation, or CTPR. Clonogenic survival assays, sulforhodamine B cytotoxity assays and cell density assays were used to assess the effectiveness of each therapy in vitro. Measurements of apoptosis, cell cycle analysis by flow cytometry and Western blots were used to evaluate mechanisms of action in vitro. Tumor growth delay assays were used to evaluate radiation induced tumor responses in vivo.

Results

In vitro, CTPR had greater inhibitory effects on prostate cancer cell viability and clonogenic survival than either perifosine or radiation treatment alone. A marked increase in prostate cancer cell apoptosis was noted in CTPR. Phosphorylation of AKT-T308 AKT and S473 were decreased when using perifosine treatment or CTPR. Cleaved caspase 3 was significantly increased in the CTPR group. In vivo, CTPR had greater inhibitory effects on the growth of xenografts when compared with perifosine or radiation treatment alone groups.

Conclusions

Perifosine enhances prostate cancer radiosensitivity in vitro and in vivo. These data provide strong support for further development of this combination therapy in clinical studies.
VEGF attenuates development from cardiac hypertrophy to heart failure after aortic stenosis through mitochondrial mediated apoptosis and cardiomyocyte proliferation
Authors: Xu Xiao H , Xu Jing , Xue Lei , Cao Hai L , Liu Xiang , Chen Yi J
Published: April 2011

Background

Aortic stenosis (AS) affects 3 percent of persons older than 65 years and leads to greater morbidity and mortality than other cardiac valve diseases. Surgery with aortic valve replacement (AVR) for severe symptomatic AS is currently the only treatment option. Unfortunately, in patients with poor ventricular function, the mortality and long-term outcome is unsatisfied, and only a minority of these patients could bear surgery. Our previous studies demonstrated that vascular endothelial growth factor (VEGF) protects cardiac function in myocardial infarction model through classic VEGF-PI3k-Akt and unclear mitochondrial anti-apoptosis pathways; promoting cardiomyocyte (CM) proliferation as well. The present study was designed to test whether pre-operative treatment with VEGF improves AS-induced cardiac dysfunction, to be better suitable for AVR, and its potential mechanism.

Methods

Adult male mice were subjected to AS or sham operation. Two weeks later, adenoviral VEGF (Ad-VEGF), enhanced green fluorescence protein (Ad-EGFP, as a parallel control) or saline was injected into left ventricle free wall. Two weeks after delivery, all mice were measured by echocardiography and harvested for further detection.

Results

AS for four weeks caused cardiac hypertrophy and left ventricular dysfunction. VEGF treatment increased capillary density, protected mitochondrial function, reduced CMs apoptosis, promoted CMs proliferation and eventually preserved cardiac function.

Conclusions

Our findings indicate that VEGF could repair AS-induced transition from compensatory cardiac hypertrophy to heart failure.
Hierarchies in eukaryotic genome organization: Insights from polymer theory and simulations
Authors: Iyer Balaji VS , Kenward Martin , Arya Gaurav
Published: April 2011

Eukaryotic genomes possess an elaborate and dynamic higher-order structure within the limiting confines of the cell nucleus. Knowledge of the physical principles and the molecular machinery that govern the 3D organization of this structure and its regulation are key to understanding the relationship between genome structure and function. Elegant microscopy and chromosome conformation capture techniques supported by analysis based on polymer models are important steps in this direction. Here, we review results from these efforts and provide some additional insights that elucidate the relationship between structure and function at different hierarchical levels of genome organization.
High-dose tranexamic acid reduces blood loss in postpartum haemorrhage
Authors: Ducloy-Bouthors Anne-Sophie , Jude Brigitte , Duhamel Alain , Broisin Françoise , Huissoud Cyril , Keita-Meyer Hawa , Mandelbrot Laurent , Tillouche Nadia , Fontaine Sylvie , Le Goueff Françoise , Depret-Mosser Sandrine , Vallet Benoit ,   The EXADELI Study Group, Susen Sophie
Published: April 2011

Introduction

Our purpose in conducting this study was to determine whether administration of high-dose tranexamic acid (TA) at the time of diagnosis of postpartum haemorrhage (PPH) could reduce blood loss.

Methods

This was a randomised, controlled, multicentred, open-label trial. Women with PPH >800 mL following vaginal delivery were randomly assigned to receive TA (loading dose 4 g over 1 hour, then infusion of 1 g/hour over 6 hours) or not. In both groups, packed red blood cells (PRBCs) and colloids could be used according to French guidelines. The use of additional procoagulant treatments was permitted only in cases involving intractable bleeding. The primary objective was to assess the efficacy of TA in the reduction of blood loss in women with PPH, and the secondary objectives were the effect of TA on PPH duration, anaemia, transfusion and the need for invasive procedures.

Results

A total of 144 women fully completed the protocol (72 in each group). Blood loss between enrolment and 6 hours later was significantly lower in the TA group than in the control group (median, 173 mL; first to third quartiles, 59 to 377) than in controls (221 mL; first to third quartiles 105 to 564) (P = 0.041). In the TA group, bleeding duration was shorter and progression to severe PPH and PRBC transfusion was less frequent than in controls (P < 0.03). Invasive procedures were performed in four women in the TA group and in seven controls (P = NS). PPH stopped after only uterotonics and PRBC transfusion in 93% of women in the TA group versus 79% of controls (P = 0.016). Mild, transient adverse manifestations occurred more often in the TA group than in the control group (P = 0.03).

Conclusions

This study is the first to demonstrate that high-dose TA can reduce blood loss and maternal morbidity in women with PPH. Although the study was not adequately powered to address safety issues, the observed side effects were mild and transient. A larger international study is needed to investigate whether TA can decrease the need for invasive procedures and reduce maternal morbidity in women with PPH.

Trial registration

Controlled Trials ISRCTN09968140.
Comparison of depressive episodes in bipolar disorder and in major depressive disorder within bipolar disorder pedigrees
Authors: Mitchell Philip B. , Frankland Andrew , Hadzi-Pavlovic Dusan , Roberts Gloria , Corry Justine , Wright Adam , Loo Colleen K. , Breakspear Michael
Published: April 2011

Background

Although genetic epidemiological studies have confirmed increased rates of major depressive disorder among the relatives of people with bipolar affective disorder, no report has compared the clinical characteristics of depression between these two groups.

Aims

To compare clinical features of depressive episodes across participants with major depressive disorder and bipolar disorder from within bipolar disorder pedigrees, and assess the utility of a recently proposed probabilistic approach to distinguishing bipolar from unipolar depression. A secondary aim was to identify subgroups within the relatives with major depression potentially indicative of ‘genetic’ and ‘sporadic’ subgroups.

Method

Patients with bipolar disorder types 1 and 2 (n = 246) and patients with major depressive disorder from bipolar pedigrees (n = 120) were assessed using the Diagnostic Interview for Genetic Studies. Logistic regression was used to identify distinguishing clinical features and assess the utility of the probabilistic approach. Hierarchical cluster analysis was used to identify subgroups within the major depressive disorder sample.

Results

Bipolar depression was characterised by significantly higher rates of psychomotor retardation, difficulty thinking, early morning awakening, morning worsening and psychotic features. Depending on the threshold employed, the probabilistic approach yielded a positive predictive value ranging from 74% to 82%. Two clusters within the major depressive disorder sample were found, one of which demonstrated features characteristic of bipolar depression, suggesting a possible ‘genetic’ subgroup.

Conclusions

A number of previously identified clinical differences between unipolar and bipolar depression were confirmed among participants from within bipolar disorder pedigrees. Preliminary validation of the probabilistic approach in differentiating between unipolar and bipolar depression is consistent with dimensional distinctions between the two disorders and offers clinical utility in identifying patients who may warrant further assessment for bipolarity. The major depressive disorder clusters potentially reflect genetic and sporadic subgroups which, if replicated independently, might enable an improved phenotypic definition of underlying bipolarity in genetic analyses.
Functional 20S proteasomes in mature human red blood cells
Authors: Neelam Sudha , Kakhniashvili David G , Wilkens Stephan , Levene Stephen D , Goodman Steven R
Published: April 2011

The purpose of the present study was to investigate whether functional 20S and/or 26S proteasomes are present within mature human red blood cells (RBCs; depleted of reticulocytes and leukocytes). Double-immunofluorescence confocal microscopy showed the presence of immunoreactive 20S and 19S proteasomal subunit proteins and their partial co-localization within mature RBCs. Proteasomes isolated from mature RBCs displayed 20S activity in vitro; atomic-force and transmission electron microscopy of isolated proteasomes revealed abundant 20S core particles and very few 26S particles. A two-dimensional differential in-gel electrophoresis (2D-DIGE) approach was used to determine if proteasome-dependent protein degradation occurs within mature RBCs. Twenty-eight proteins were identified with altered protein content in response to lactacystin. Seven cytosolic proteins showed an increase and 16 showed a decrease; five membrane proteins showed a decrease. We conclude that the proteins showing increased abundance are either primary or secondary targets of the 20S proteasome and that putatively degraded proteins are secondary targets. Therefore, functional 20S proteasomes exist within mature RBCs. Our study did not detect 26S proteasome activity using the 2D-DIGE approach.
Infectious microorganisms in mice (Mus musculus) purchased from commercial pet shops in Germany
Authors: Dammann P , Hilken G , Hueber B , Köhl W , Bappert M T , Mähler M
Published: April 2011

In this study, we investigated the prevalence of infectious microorganisms (viruses, bacteria, fungi and eukaryotic parasites) in mice from different pet shops in Germany; such animals may compromise the hygienic integrity of laboratory animal vivaria if private pet holders act as unintended vectors of infections carried by them. House mice sold as pets or feed specimens were purchased from different pet shops and tested for a comprehensive panel of unwanted microorganisms. We found a number of microorganisms in these pet shop mice, the most prevalent of which were Helicobacter species (92.9%), mouse parvovirus (89.3%), mouse hepatitis virus (82.7%), Pasteurella pneumotropica (71.4%) and Syphacia species (57.1 %). Several microorganisms (e.g. mouse parvovirus, Theiler's murine encephalomyelitis virus, pneumonia virus of mice, Encephalitozoon cuniculi, Clostridium piliforme) had considerably higher prevalences than those reported in similar studies on wild mice from North America, Europe or Australia. Our study shows that direct contact with pet shop mice may constitute a risk for laboratory animal vivaria if hygienic precautions are not taken. However, even relatively simple precautions seem effective enough to hold the risk at bay.