bluuebunny/crossref_metadata_2025 huggingface dataset:
The utilization of antenatal care among rural-to-urban migrant women in Shanghai:a hospital-based cross-sectional study
Authors: Zhao Qi , Huang Zhihuan Jennifer , Yang Sijia , Pan Jie , Smith Brian , Xu Biao
Published: November 2012

Background

Improving utilization of antenatal care is a critical strategy for achieving China’s Millennium Development Goal of decreasing the maternal mortality ratio (MMR). While overall utilization has increased recently in China, an urban vs. rural disparity in access remains. Here we aim to assess utilization of antenatal care in rural-to-urban migrant women and identify its risk and protective factors.

Methods

Migrant women who had been living in Shanghai for more than six months, delivered in one of the two study hospitals between August 2009 and February 2010, and provided written consent were interviewed using a structured questionnaire.

Results

Of 767 women, 90.1% (691) made at least one antenatal care visit, while 49.7% (381) had adequately utilized antenatal care (i.e., made five or more antenatal care visits). Only 19.7% of women visited an antenatal care center during the first trimester (12 weeks). Women between the ages of 25 and 30 and women older than 30 were more likely than younger women to have adequately utilized antenatal care (AOR=2.2 and 1.9, 95%CI=1.4-3.5 and 1.1-3.2, respectively). Women whose husbands held Shanghai residency status (AOR=4.9, 95%CI=2.2-10.9) or who had more than 10 years of education (AOR=1.8, 95%CI=1.2-2.9), previously experienced a miscarriage or abortion (AOR=2.2, 95%CI=1.3-3.8), had higher household income (AOR=1.6, 95%CI=1.0-2.5) were more likely to have adequately utilized antenatal care. Women from high-income households were also more likely to receive antenatal care during the first 12 weeks (AOR=3.5, 95%CI=1.7-5.5).

Conclusions

Many migrant women in Shanghai did not receive adequate antenatal care and initiated antenatal care later than the optimal first 12 weeks of pregnancy. Poor antenatal care utilization was associated with low socioeconomic status, education, and certain demographic factors. Tailored health education for both migrant women and their husbands should be strengthened to improve maternal health. Financing supports should be provided to improve the utilization of antenatal care.
Ovarian cancer ascites increase Mcl-1 expression in tumor cells through ERK1/2-Elk-1 signaling to attenuate TRAIL-induced apoptosis
Authors: Goncharenko-Khaider Nadzeya , Matte Isabelle , Lane Denis , Rancourt Claudine , Piché Alain
Published: November 2012

Background

Ascites may affect the progression of ovarian cancer (OC). In particular, soluble factors present in OC ascites can create a protective environment for tumor cells that promotede novoresistance to drug- and death receptor-induced apoptosis. However, the underlying molecular mechanisms responsible for ascites-induced drug resistance are not well characterized.

Methods

Using human OC cell lines and tissues microarrays of human OC biopsies, we assessed the mechanism by which OC ascites increase Mcl-1 expression using Western blots, chemical inhibitors of ERK and small-inhibitory RNA treatments.

Results

In the present study, we found that both Mcl-1 mRNA and protein levels were upregulated within 2 h upon treatment of OC cells with ascites obtained from women with advanced OC. In contrast, the expression of other Bcl-2 family antiapoptotic members such as Bcl-2 and Bcl-XLwas not affected by ascites. An increase of Mcl-1 expression was consistently observed across different ascites from women with advanced serous OC. The knockdown of Mcl-1 significantly blocked ascites-induced Mcl-1 upregulation and ascites-mediated inhibition of TRAIL-induced apoptosis. Ascites induced a rapid phosphorylation of ERK1/2 and Elk-1 transcription factor. Furthermore, we found that ERK1/2 inhibition or Elk-1 knockdown was sufficient to block ascites-induced Mcl-1 expression. In high grade serous OC, we found a positive correlation between phosphorylated ERK1/2 and Mcl-1 expression.

Conclusions

These results indicate that ascites-induced ERK1/2/Elk-1 signaling is critical for Mcl-1 expression and for the ascites-mediated attenuation of TRAIL-induced apoptosis. The ERK1/2/Elk-1/Mcl-1 pathway represents a novel mechanism by which ascites inducede novoTRAIL resistance in OC cells.
An investigation of excess residual cytoplasm in human spermatozoa and its distinction from the cytoplasmic droplet
Authors: Rengan Anil K , Agarwal Ashok , van der Linde Michelle , du Plessis Stefan S
Published: November 2012

Recent studies have shown cytoplasmic droplets to be normal morphological occurrences in human male spermatozoa. When the cytoplasm around the sperm midpiece is present in large amounts, however, pathological effects may transpire. The cytoplasmic droplet then becomes known as excess residual cytoplasm, which can impair overall sperm function and produce higher levels of reactive oxygen species, potentially leading to male infertility. Though the distinction between cytoplasmic droplets and excess residual cytoplasm has been made, some studies fail to recognize the difference and incorrectly label the latter as a cytoplasmic droplet. This review attempts to clarify excess residual cytoplasm’s effect on fertility, examine the enzymes responsible, and suggest tests and possible treatment options for those affected by this defect.
An emerging role for microRNAs in NF1 tumorigenesis
Authors: Sedani Ashni , Cooper David N , Upadhyaya Meena
Published: November 2012

MicroRNAs (miRNAs) are a class of non-coding RNA, which have recently been shown to have a wide variety of regulatory functions in relation to gene expression. Since their identification nearly 20 years ago, miRNAs have been found to play an important role in cancer, including in neurofibromatosis type 1 (NF1)-associated tumours. NF1 is the most commonly inherited tumour predisposition syndrome and can lead to malignancy via the development of malignant peripheral nerve sheath tumours (MPNSTs). Although the mechanisms by which benign neurofibromas develop into MPNSTs still remain to be elucidated, it is becoming increasingly clear that miRNAs play a key role in this process and have the potential to be used as both diagnostic and prognostic markers of tumorigenesis.
Regulation of podosome formation, microglial migration and invasion by Ca2+-signaling molecules expressed in podosomes
Authors: Siddiqui Tamjeed A , Lively Starlee , Vincent Catherine , Schlichter Lyanne C
Published: November 2012

Background

Microglia migrate during brain development and after CNS injury, but it is not known how they degrade the extracellular matrix (ECM) to accomplish this. Podosomes are tiny structures with the unique ability to adhere to and dissolve ECM. Podosomes have a two-part architecture: a core that is rich in F-actin and actin-regulatory molecules (for example, Arp2/3), surrounded by a ring with adhesion and structural proteins (for example, talin, vinculin). We recently discovered that the lamellum at the leading edge of migrating microglia contains a large F-actin-rich superstructure (‘podonut’) composed of many podosomes. Microglia that expressed podosomes could degrade ECM molecules. Finely tuned Ca2+ signaling is important for cell migration, cell-substrate adhesion and contraction of the actomyosin network. Here, we hypothesized that podosomes contain Ca2+-signaling machinery, and that podosome expression and function depend on Ca2+ influx and specific ion channels.

Methods

High-resolution immunocytochemistry was used on rat microglia to identify podosomes and novel molecular components. A pharmacological toolbox was applied to functional assays. We analyzed roles of Ca2+-entry pathways and ion channels in podosome expression, microglial migration into a scratch-wound, transmigration through pores in a filter, and invasion through Matrigel™-coated filters.

Results

Microglial podosomes were identified using well-known components of the core (F-actin, Arp2) and ring (talin, vinculin). We discovered four novel podosome components related to Ca2+ signaling. The core contained calcium release activated calcium (CRAC; Orai1) channels, calmodulin, small-conductance Ca2+-activated SK3 channels, and ionized Ca2+ binding adapter molecule 1 (Iba1), which is used to identify microglia in the CNS. The Orai1 accessory molecule, STIM1, was also present in and around podosomes. Podosome formation was inhibited by removing external Ca2+ or blocking CRAC channels. Blockers of CRAC channels inhibited migration and invasion, and SK3 inhibition reduced invasion.

Conclusions

Microglia podosome formation, migration and/or invasion require Ca2+ influx, CRAC, and SK3 channels. Both channels were present in microglial podosomes along with the Ca2+-regulated molecules, calmodulin, Iba1 and STIM1. These results suggest that the podosome is a hub for sub-cellular Ca2+-signaling to regulate ECM degradation and cell migration. The findings have broad implications for understanding migration mechanisms of cells that adhere to, and dissolve ECM.
Association of dimethylarginines and mediators of inflammation after acute ischemic stroke
Authors: Chen Shufen , Martens-Lobenhoffer Jens , Weissenborn Karin , Kielstein Jan T , Lichtinghagen Ralf , Deb-Chatterji Milani , Li Na , Tryc Anita B , Goldbecker Annemarie , Dong Qiang , Bode-Böger Stefanie M , Worthmann Hans
Published: November 2012

Background

Elevated levels of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) are accompanied by endothelial dysfunction and predict adverse outcome after ischemic stroke. Via induction of oxidative stress, dimethylarginines are possibly linked to the inflammatory cascade after stroke that is known to considerably contribute to secondary progression of brain injury. We sought to investigate the association between dimethylarginines and inflammatory mediators in patients with acute ischemic stroke.

Methods

Plasma levels of ADMA and SDMA were measured in prospectively collected blood samples of 58 patients with acute ischemic stroke. Blood samples were taken at 6 hours, 12 hours, 24 hours, 3 days and 7 days after onset of symptoms. Analyses of ADMA and SDMA were done by high-performance liquid chromatography-tandem mass spectrometry. Monocyte chemotactic protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), interleukin-6 (IL-6), C-reactive protein (CRP) and S100B as markers of inflammation and brain damage were determined by commercially available immunometric assays. Patient data were compared with control data from 32 age-adjusted healthy volunteers. Baseline stroke severity was evaluated by the National Institutes of Health Stroke Scale (NIHSS) (NIHSS 0 to 1: mild stroke; NIHSS 2 to 8: moderate stroke; NIHSS ≥9: severe stroke).

Results

Plasma ADMA and SDMA levels significantly correlated with blood levels of inflammatory mediators up to day 7 after stroke. On multiple stepwise linear regression analysis ADMA correlated with TIMP-1 at 6 hours, 24 hours, 3 days and 7 days, MMP-9 at 12 hours and IL-6 at 7 days (P <0.05) while SDMA correlated with MCP-1 at 6 hours, 24 hours, 3 days and 7 days as well as IL-6 at 3 days and 7 days (P <0.05).

Conclusions

The levels of the vasoactive compound ADMA as well as levels of its structural isomer SDMA are associated with levels of inflammatory mediators after acute ischemic stroke. Further studies need to elucidate the cause and effect relationship of these crucial players.
Iron deficiency causes a shift in AMP-activated protein kinase (AMPK) subunit composition in rat skeletal muscle
Authors: Merrill John F , Thomson David M , Hardman Shalene E , Hepworth Squire D , Willie Shelby , Hancock Chad R
Published: November 2012

Background

As a cellular energy sensor, the 5’AMP-activated protein kinase (AMPK) is activated in response to energy stresses such as hypoxia and muscle contraction. To determine effects of iron deficiency on AMPK activation and signaling, as well as the AMPK subunit composition in skeletal muscle, rats were fed a control (C=50-58 mg/kg Fe) or iron deficient (ID=2-6 mg/kg Fe) diet for 6–8 wks.

Results

Their respective hematocrits were 47.5% ± 1.0 and 16.5% ± 0.6. Iron deficiency resulted in 28.3% greater muscle fatigue (p<0.01) in response to 10 min of stimulation (1 twitch/sec) and was associated with a greater reduction in phosphocreatine (C: Resting 24.1 ± 0.9 μmol/g, Stim 13.1 ± 1.5 μmol/g; ID: Resting 22.7 ± 1.0 μmol/g, Stim 3.2 ± 0.7 μmol/g; p<0.01) and ATP levels (C: Resting 5.89 ± 0.48 μmol/g, Stim 6.03 ± 0.35 μmol/g; ID: Resting 5.51 ± 0.20 μmol/g, Stim 4.19 ± 0.47 μmol/g; p<0.05). AMPK activation increased with stimulation in muscles of C and ID animals. A reduction in Cytochrome c and other iron-dependent mitochondrial proteins was observed in ID animals (p<0.01). The AMPK catalytic subunit (α) was examined because both isoforms are known to play different roles in responding to energy challenges. In ID animals, AMPKα2 subunit protein content was reduced to 71.6% of C (p<0.05), however this did not result in a significant difference in resting AMPKα2 activity. AMPKα1 protein was unchanged, however an overall increase in AMPKα1 activity was observed (C: 0.91 pmol/mg/min; ID: 1.63 pmol/mg/min; p<0.05). Resting phospho Acetyl CoA Carboxylase (pACC) was unchanged. In addition, we observed significant reductions in the β2 and γ3 subunits of AMPK in response to iron deficiency.

Conclusions

This study indicates that chronic iron deficiency causes a shift in the expression of AMPKα, β, and γ subunit composition. Iron deficiency also causes chronic activation of AMPK as well as an increase in AMPKα1 activity in exercised skeletal muscle.
Primary cervical hydatid cyst: a rare occurrence
Authors: Sultana Nuzhat , Hashim Tariq Khan , Jan Shahida Yahya , khan Zahidullah , Malik Tahir , Shah Walayat
Published: November 2012

Hydatid disease, a parasitic infection is caused by Echinococcus granulosus. It has serious impact on health and economy especially in countries where it is endemic. It occurs frequently in liver and lung. The disease is chronic and cyst can localize in different organs. A hydatid cyst occurrence in the head and neck is extremely rare. To know the distribution of disease can help in its control and prevention. We report a case of primary cervical hydatid cyst in 20 year old female. A high index of suspicion is required to diagnose hydatid cyst in rare locations like this. Hydatid cyst should be considered in differential diagnosis of benign swellings of head and neck region, so that it can be managed during surgery to prevent acute anaphylaxis.

Virtual slides

The virtual slides’ for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4915595218376646
GraphAlignment: Bayesian pairwise alignment of biological networks
Authors: Kolář Michal , Meier Jörn , Mustonen Ville , Lässig Michael , Berg Johannes
Published: November 2012

Background

With increased experimental availability and accuracy of bio-molecular networks, tools for their comparative and evolutionary analysis are needed. A key component for such studies is the alignment of networks.

Results

We introduce the Bioconductor package GraphAlignment for pairwise alignment of bio-molecular networks. The alignment incorporates information both from network vertices and network edges and is based on an explicit evolutionary model, allowing inference of all scoring parameters directly from empirical data. We compare the performance of our algorithm to an alternative algorithm, Græmlin 2.0.

On simulated data, GraphAlignment outperforms Græmlin 2.0 in several benchmarks except for computational complexity. When there is little or no noise in the data, GraphAlignment is slower than Græmlin 2.0. It is faster than Græmlin 2.0 when processing noisy data containing spurious vertex associations. Its typical case complexity grows approximately as

O
(

N

2
.
6

)

.

On empirical bacterial protein-protein interaction networks (PIN) and gene co-expression networks, GraphAlignment outperforms Græmlin 2.0 with respect to coverage and specificity, albeit by a small margin. On large eukaryotic PIN, Græmlin 2.0 outperforms GraphAlignment.

Conclusions

The GraphAlignment algorithm is robust to spurious vertex associations, correctly resolves paralogs, and shows very good performance in identification of homologous vertices defined by high vertex and/or interaction similarity. The simplicity and generality of GraphAlignment edge scoring makes the algorithm an appropriate choice for global alignment of networks.
Generation of Trichoderma atroviride mutants with constitutively activated G protein signaling by using geneticin resistance as selection marker
Authors: Gruber Sabine , Omann Markus , Rodrìguez Carolina Escobar , Radebner Theresa , Zeilinger Susanne
Published: November 2012

Background

Species of the fungal genus Trichoderma are important industrial producers of cellulases and hemicellulases, but also widely used as biocontrol agents (BCAs) in agriculture. In the latter function Trichoderma species stimulate plant growth, induce plant defense and directly antagonize plant pathogenic fungi through their mycoparasitic capabilities. The recent release of the genome sequences of four mycoparasitic Trichoderma species now forms the basis for large-scale genetic manipulations of these important BCAs. Thus far, only a limited number of dominant selection markers, including Hygromycin B resistance (hph) and the acetamidase-encoding amdS gene, have been available for transformation of Trichoderma spp. For more extensive functional genomics studies the utilization of additional dominant markers will be essential.

Results

We established the Escherichia coli neomycin phosphotransferase II-encoding nptII gene as a novel selectable marker for the transformation of Trichoderma atroviride conferring geneticin resistance. The nptII marker cassette was stably integrated into the fungal genome and transformants exhibited unaltered phenotypes compared to the wild-type. Co-transformation of T. atroviride with nptII and a constitutively activated version of the Gα subunit-encoding tga3 gene (tga3

Q207L
) resulted in a high number of mitotically stable, geneticin-resistant transformants. Further analyses revealed a co-transformation frequency of 68% with 15 transformants having additionally integrated tga3

Q207L
into their genome. Constitutive activation of the Tga3-mediated signaling pathway resulted in increased vegetative growth and an enhanced ability to antagonize plant pathogenic host fungi.

Conclusion

The neomycin phosphotransferase II-encoding nptII gene from Escherichia coli proved to be a valuable tool for conferring geneticin resistance to the filamentous fungus T. atroviride thereby contributing to an enhanced genetic tractability of these important BCAs.
Antibiotic prescription patterns in the empiric therapy of severe sepsis: combination of antimicrobials with different mechanisms of action reduces mortality
Authors: Díaz-Martín Ana , Martínez-González María Luisa , Ferrer Ricard , Ortiz-Leyba Carlos , Piacentini Enrique , Lopez-Pueyo Maria Jesus , Martín-Loeches Ignacio , Levy Mitchell M , Artigas Antoni , Garnacho-Montero José ,   for the Edusepsis Study Group
Published: November 2012

Introduction

Although early institution of adequate antimicrobial therapy is lifesaving in sepsis patients, optimal antimicrobial strategy has not been established. Moreover, the benefit of combination therapy over monotherapy remains to be determined. Our aims are to describe patterns of empiric antimicrobial therapy in severe sepsis, assessing the impact of combination therapy, including antimicrobials with different mechanisms of action, on mortality.

Methods

This is a Spanish national multicenter study, analyzing all patients admitted to ICUs who received antibiotics within the first 6 hours of diagnosis of severe sepsis or septic shock. Antibiotic-prescription patterns in community-acquired infections and nosocomial infections were analyzed separately and compared. We compared the impact on mortality of empiric antibiotic treatment, including antibiotics with different mechanisms of action, termed different-class combination therapy (DCCT), with that of monotherapy and any other combination therapy possibilities (non-DCCT).

Results

We included 1,372 patients, 1,022 (74.5%) of whom had community-acquired sepsis and 350 (25.5%) of whom had nosocomial sepsis. The most frequently prescribed antibiotic agents were β-lactams (902, 65.7%) and carbapenems (345, 25.1%). DCCT was administered to 388 patients (28.3%), whereas non-DCCT was administered to 984 (71.7%). The mortality rate was significantly lower in patients administered DCCTs than in those who were administered non-DCCTs (34% versus 40%; P = 0.042). The variables independently associated with mortality were age, male sex, APACHE II score, and community origin of the infection. DCCT was a protective factor against in-hospital mortality (odds ratio (OR), 0.699; 95% confidence interval (CI), 0.522 to 0.936; P = 0.016), as was urologic focus of infection (OR, 0.241; 95% CI, 0.102 to 0.569; P = 0.001).

Conclusions

β-Lactams, including carbapenems, are the most frequently prescribed antibiotics in empiric therapy in patients with severe sepsis and septic shock. Administering a combination of antimicrobials with different mechanisms of action is associated with decreased mortality.
InSilico DB genomic datasets hub: an efficient starting point for analyzing genome-wide studies in GenePattern, Integrative Genomics Viewer, and R/Bioconductor
Authors: Coletta Alain , Molter Colin , Duqué Robin , Steenhoff David , Taminau Jonatan , de Schaetzen Virginie , Meganck Stijn , Lazar Cosmin , Venet David , Detours Vincent , Nowé Ann , Bersini Hugues , Weiss Solís David Y
Published: November 2012

Genomics datasets are increasingly useful for gaining biomedical insights, with adoption in the clinic underway. However, multiple hurdles related to data management stand in the way of their efficient large-scale utilization. The solution proposed is a web-based data storage hub. Having clear focus, flexibility and adaptability, InSilico DB seamlessly connects genomics dataset repositories to state-of-the-art and free GUI and command-line data analysis tools. The InSilico DB platform is a powerful collaborative environment, with advanced capabilities for biocuration, dataset sharing, and dataset subsetting and combination. InSilico DB is available from https://insilicodb.org.
A phenotypic screening platform to identify small molecule modulators of Chlamydomonas reinhardtiigrowth, motility and photosynthesis
Authors: Alfred Simon E , Surendra Anuradha , Le Chris , Lin Ken , Mok Alexander , Wallace Iain M , Proctor Michael , Urbanus Malene L , Giaever Guri , Nislow Corey
Published: November 2012

Chemical biology, the interfacial discipline of using small molecules as probes to investigate biology, is a powerful approach of developing specific, rapidly acting tools that can be applied across organisms. The single-celled alga Chlamydomonas reinhardtii is an excellent model system because of its photosynthetic ability, cilia-related motility and simple genetics. We report the results of an automated fitness screen of 5,445 small molecules and subsequent assays on motility/phototaxis and photosynthesis. Cheminformatic analysis revealed active core structures and was used to construct a naïve Bayes model that successfully predicts algal bioactive compounds.
Hog1 bypasses stress-mediated down-regulation of transcription by RNA polymerase II redistribution and chromatin remodeling
Authors: Nadal-Ribelles Mariona , Conde Núria , Flores Oscar , González-Vallinas Juan , Eyras Eduardo , Orozco Modesto , de Nadal Eulàlia , Posas Francesc
Published: November 2012

Background

Cells are subjected to dramatic changes of gene expression upon environmental changes. Stress causes a general down-regulation of gene expression together with the induction of a set of stress-responsive genes. The p38-related stress-activated protein kinase Hog1 is an important regulator of transcription upon osmostress in yeast.

Results

Genome-wide localization studies of RNA polymerase II (RNA Pol II) and Hog1 showed that stress induced major changes in RNA Pol II localization, with a shift toward stress-responsive genes relative to housekeeping genes. RNA Pol II relocalization required Hog1, which was also localized to stress-responsive loci. In addition to RNA Pol II-bound genes, Hog1 also localized to RNA polymerase III-bound genes, pointing to a wider role for Hog1 in transcriptional control than initially expected. Interestingly, an increasing association of Hog1 with stress-responsive genes was strongly correlated with chromatin remodeling and increased gene expression. Remarkably, MNase-Seq analysis showed that although chromatin structure was not significantly altered at a genome-wide level in response to stress, there was pronounced chromatin remodeling for those genes that displayed Hog1 association.

Conclusion

Hog1 serves to bypass the general down-regulation of gene expression that occurs in response to osmostress, and does so both by targeting RNA Pol II machinery and by inducing chromatin remodeling at stress-responsive loci.
Comprehensive analysis of the genome transcriptome and proteome landscapes of three tumor cell lines
Authors: Akan Pelin , Alexeyenko Andrey , Costea Paul Igor , Hedberg Lilia , Solnestam Beata Werne , Lundin Sverker , Hällman Jimmie , Lundberg Emma , Uhlén Mathias , Lundeberg Joakim
Published: November 2012

We here present a comparative genome, transcriptome and functional network analysis of three human cancer cell lines (A431, U251MG and U2OS), and investigate their relation to protein expression. Gene copy numbers significantly influenced corresponding transcript levels; their effect on protein levels was less pronounced. We focused on genes with altered mRNA and/or protein levels to identify those active in tumor maintenance. We provide comprehensive information for the three genomes and demonstrate the advantage of integrative analysis for identifying tumor-related genes amidst numerous background mutations by relating genomic variation to expression/protein abundance data and use gene networks to reveal implicated pathways.
CD4+ T lymphocytes in lung fibrosis: diverse subsets, diverse functions
Authors: Lo Re Sandra , Lison Dominique , Huaux François
Published: November 2012

Review on the function of CD4+ T lymphocyte subsets in lung fibrosis development.

The discovery of several subsets of CD4+ Th lymphocytes has contributed to refine and to challenge our understanding of the roles of CD4+ T cells in the pathogenesis of fibrotic lung diseases. Here, we review recent findings, indicating that CD4+ T subpopulations possess contrasting pro- and antifibrotic activities in human and experimental lung fibrosis. Special attention is given to delineate the activity of the newly discovered CD4+ T lymphocyte subsets (Tregs, Th22, and Th9) on fibroblast function and matrix deposition through the release of growth factors, cytokines, and eicosanoids. It appears that the function of a CD4+ T lymphocyte subset or of a cytokine can differ with the disease stage (acute vs. chronic), pulmonary localization (bronchial vs. alveolar), cellular level (epithelial cell vs. fibroblast), or immune environment (inflammatory or immunosuppressive). Integrating our recent understanding of the contrasting functions of T lymphocyte subsets in fibrosis provides new insights and opportunities for improved treatment strategies.
Caspase-8 and caspase-9 mediate thymocyte apoptosis in Trypanosoma cruzi acutely infected mice
Authors: Farias-de-Oliveira Désio Aurélio , Villa-Verde Déa Maria Serra , Nunes Panzenhagen Pedro Henrique , Silva dos Santos Danielle , Berbert Luiz Ricardo , Savino Wilson , de Meis Juliana
Published: November 2012

Thymus atrophy and thymocyte apoptosis during T. cruzi infection is mediated by both the extrinsic and intrinsic death pathway, and involves caspase activation.

Trypanosoma cruzi acute infection leads to thymic atrophy, largely as a result of death of immature DP T cells. In a second vein, the glucocorticoid hormone imbalance promotes DP T cell apoptosis in infected mice. Herein, we assessed the involvement of caspase signaling in thymocyte death during T. cruzi acute infection. BALB/c mice were infected i.p. with 102 trypomastigote forms of T. cruzi and analyzed from 7 to 19 dpi. Thymocyte apoptosis was observed in early stages of infection, increasing along with time postinfection. Immature DN and DP as well as CD4+ and CD8+ thymocytes from infected mice showed increased activation of caspase-8, -9, and -3. In vitro treatment of thymocytes from infected mice with a general caspase inhibitor or the combination of caspase-8- and caspase-9-specific inhibitors increased the number of living thymocytes. Intrathymic injection of the general caspase inhibitor, but not caspase-8 or -9 inhibitors individually, prevented thymic atrophy and thymocyte depletion in infected mice. Moreover, blockade of glucocorticoid receptor activity with RU486 prevented DP thymocyte apoptosis, together with caspase-8 and -9 activation. These findings indicate that DP T cell apoptosis following experimental T. cruzi acute infection is dependent on glucocorticoid stimulation, promoting caspase-8 and -9 activation.
Ras-dva Is a Novel Pit-1- and Glucocorticoid-Regulated Gene in the Embryonic Anterior Pituitary Gland
Authors: Ellestad Laura E. , Porter Tom E.
Published: November 2012

Glucocorticoids play a role in functional differentiation of pituitary somatotrophs and lactotrophs during embryogenesis. Ras-dva was identified as a gene regulated by anterior neural fold protein-1/homeobox expressed in embryonic stem cells-1, a transcription factor known to be critical in pituitary development, and has an expression profile in the chicken embryonic pituitary gland that is consistent with in vivo regulation by glucocorticoids. The objective of this study was to characterize expression and regulation of ras-dva mRNA in the developing chicken anterior pituitary. Pituitary ras-dva mRNA levels increased during embryogenesis to a maximum on embryonic day (e) 18 and then decreased and remained low or undetectable after hatch. Ras-dva expression was highly enriched in the pituitary gland on e18 relative to other tissues examined. Glucocorticoid treatment of pituitary cells from mid- and late-stage embryos rapidly increased ras-dva mRNA, suggesting it may be a direct transcriptional target of glucocorticoids. A reporter construct driven by 4 kb of the chicken ras-dva 5′-flanking region, containing six putative pituitary-specific transcription factor-1 (Pit-1) binding sites and two potential glucocorticoid receptor (GR) binding sites, was highly activated in embryonic pituitary cells and up-regulated by corticosterone. Mutagenesis of the most proximal Pit-1 site decreased promoter activity in chicken e11 pituitary cells, indicating regulation of ras-dva by Pit-1. However, mutating putative GR binding sites did not substantially reduce induction of ras-dva promoter activity by corticosterone, suggesting additional DNA elements within the 5′-flanking region are responsible for glucocorticoid regulation. We have identified ras-dva as a glucocorticoid-regulated gene that is likely expressed in cells of the Pit-1 lineage within the developing anterior pituitary gland.
Persistent Subclinical Hypothyroidism and Cardiovascular Risk in the Elderly: The Cardiovascular Health Study
Authors: Hyland Kristen A. , Arnold Alice M. , Lee Jennifer S. , Cappola Anne R.
Published: November 2012

Context:

Use of a single set of thyroid function tests to define subclinical hypothyroidism may lead to misclassification over time and could influence findings from longitudinal studies.

Objective:

We assessed the risks of coronary heart disease (CHD), heart failure (HF), and cardiovascular (CV) death in older adults with persistent subclinical hypothyroidism.

Design, Setting, and Participants:

The study included 679 subclinically hypothyroid and 4184 euthyroid U.S. individuals at least 65 yr old enrolled in the Cardiovascular Health Study and not taking thyroid preparations.

Main Outcome Measure:

We measured the 10-yr risk of incident CHD, HF, and CV death from persistent subclinical hypothyroidism, overall and stratified by degree of TSH elevation (4.5–6.9, 7.0–9.9, and 10.0–19.9 mU/liter).

Results:

There was no association between persistent subclinical hypothyroidism and incident CHD [hazard ratio (HR), 1.12; 95% confidence interval (CI), 0.93–1.36], HF (HR, 1.05; 95% CI, 0.97–1.27), or CV death (HR, 1.07; 95% CI, 0.87–1.31) in adjusted analyses in which subclinical hypothyroidism was modeled as a time-varying exposure using up to four serial thyroid function tests. When subclinical hypothyroidism was stratified by degree of TSH elevation, no significant associations were found in any stratum. Findings were similar in fixed exposure analyses in which only participants with testing 2 yr apart were considered, with no association between persistent or transient subclinical hypothyroidism and incident CHD, HF, or CV death.

Conclusions:

Our data do not support increased risk of CHD, HF, or CV death in older adults with persistent subclinical hypothyroidism.
Cold acclimation increases mitochondrial oxidative capacity without inducing mitochondrial uncoupling in goldfish white skeletal muscle
Authors: Dos Santos Reinaldo Sousa , Galina Antonio , Da-Silva Wagner Seixas
Published: November 2012

Goldfish have been used for cold acclimation studies, which have focused on changes in glycolytic and oxidative enzymes or alterations in lipid composition in skeletal muscle. Here we examine the effects of cold acclimation on the functional properties of isolated mitochondria and permeabilized fibers from goldfish white skeletal muscle, focusing on understanding the types of changes that occur in the mitochondrial respiratory states. We observed that cold acclimation promoted a significant increase in the mitochondrial oxygen consumption rates. Western blot analysis showed that UCP3 was raised by ∼1.5-fold in cold-acclimated muscle mitochondria. Similarly, we also evidenced a rise in the adenine nucleotide translocase content in cold-acclimated muscle mitochondria compared to warm-acclimated mitochondria (0.96±0.05 vs 0.68±0.02 nmol carboxyatractyloside mg−1 protein). This was followed by a 2-fold increment in the citrate synthase activity, which suggests a higher mitochondrial content in cold-acclimated goldfish. Even with higher levels of UCP3 and ANT, the effects of activator (palmitate) and inhibitors (carboxyatractyloside and GDP) on mitochondrial parameters were similar in both warm- and cold-acclimated goldfish. Thus, we propose that cold acclimation in goldfish promotes an increase in functional oxidative capacity, with higher mitochondrial content without changes in the mitochondrial uncoupling pathways.
Suppressor mutations identify amino acids in PAA-1/PR65 that facilitate regulatory RSA-1/B″ subunit targeting of PP2A to centrosomes in C. elegans
Authors: Lange Karen I. , Heinrichs Jeffrey , Cheung Karen , Srayko Martin
Published: November 2012

Protein phosphorylation and dephosphorylation is a key mechanism for the spatial and temporal regulation of many essential developmental processes and is especially prominent during mitosis. The multi-subunit protein phosphatase 2A (PP2A) enzyme plays an important, yet poorly characterized role in dephosphorylating proteins during mitosis. PP2As are heterotrimeric complexes comprising a catalytic, structural, and regulatory subunit. Regulatory subunits are mutually exclusive and determine subcellular localization and substrate specificity of PP2A. At least 3 different classes of regulatory subunits exist (termed B, B′, B″) but there is no obvious similarity in primary sequence between these classes. Therefore, it is not known how these diverse regulatory subunits interact with the same holoenzyme to facilitate specific PP2A functions in vivo. The B″ family of regulatory subunits is the least understood because these proteins lack conserved structural domains. RSA-1 (regulator of spindle assembly) is a regulatory B″ subunit required for mitotic spindle assembly in Caenorhabditis elegans. In order to address how B″ subunits interact with the PP2A core enzyme, we focused on a conditional allele, rsa-1(or598ts), and determined that this mutation specifically disrupts the protein interaction between RSA-1 and the PP2A structural subunit, PAA-1. Through genetic screening, we identified a putative interface on the PAA-1 structural subunit that interacts with a defined region of RSA-1/B″. In the context of previously published results, these data propose a mechanism of how different PP2A B-regulatory subunit families can bind the same holoenzyme in a mutually exclusive manner, to perform specific tasks in vivo.
Characterization of Fragile X Mental Retardation Protein granules formation and dynamics in Drosophila
Authors: Gareau Cristina , Martel David , Coudert Laetitia , Mellaoui Samia , Mazroui Rachid
Published: November 2012

FMRP is an evolutionarily conserved protein that is highly expressed in neurons and its deficiency causes fragile X mental retardation syndrome. FMRP controls the translation of target mRNAs in part by promoting their dynamic transport in neuronal RNA granules. We have previously shown that high expression of mammalian FMRP induces formation of granules termed FMRP granules. These RNA granules are reminiscent of neuronal granules, of stress granules, as well as of the recently described in vitro-assembled granules. In contrast with mammalian FMRP, which has two paralog proteins, Drosophila FMRP (dFMRP) is encoded by a single gene that has no paralog. Using this genetically simple organism, we investigated formation and dynamics of FMRP granules. We found that increased expression of dFMRP in Drosophila cells induces the formation of dynamic dFMRP RNA granules. Mutagenesis studies identified the N-terminal protein–protein domain of dFMRP as a key determinant for FMRP granules formation. The RGG RNA binding motif of dFMRP is dispensable for dFMRP granules formation since its deletion does not prevent formation of those granules. Deletion of the RGG motif reduced, however, dFMRP trafficking between FMRP granules and the cytosol. Similarly, deletion of a large part of the KH RNA binding motif of dFMRP had no effect on formation of dFMRP-granules, but diminished the shuttling activity of dFMRP. Our results thus suggest that the mechanisms controlling formation of RNA granules and those promoting their dynamics are uncoupled. This study opens new avenues to further elucidate the molecular mechanisms controlling FMRP trafficking with its associated mRNAs in and out of RNA granules.
Macrophage migration inhibitory factor acts as a neurotrophin in the developing inner ear
Authors: Bank Lisa M. , Bianchi Lynne M. , Ebisu Fumi , Lerman-Sinkoff Dov , Smiley Elizabeth C. , Shen Yu-chi , Ramamurthy Poornapriya , Thompson Deborah L. , Roth Therese M. , Beck Christine R. , Flynn Matthew , Teller Ryan S. , Feng Luming , Llewellyn G. Nicholas , Holmes Brandon , Sharples Cyrrene , Coutinho-Budd Jaeda , Linn Stephanie A. , Chervenak Andrew P. , Dolan David F. , Benson Jennifer , Kanicki Ariane , Martin Catherine A. , Altschuler Richard , Koch Alicia E. , Jewett Ethan M. , Germiller John A. , Barald Kate F.
Published: November 2012

This study is the first to demonstrate that macrophage migration inhibitory factor (MIF), an immune system ‘inflammatory’ cytokine that is released by the developing otocyst, plays a role in regulating early innervation of the mouse and chick inner ear. We demonstrate that MIF is a major bioactive component of the previously uncharacterized otocyst-derived factor, which directs initial neurite outgrowth from the statoacoustic ganglion (SAG) to the developing inner ear. Recombinant MIF acts as a neurotrophin in promoting both SAG directional neurite outgrowth and neuronal survival and is expressed in both the developing and mature inner ear of chick and mouse. A MIF receptor, CD74, is found on both embryonic SAG neurons and adult mouse spiral ganglion neurons. Mif knockout mice are hearing impaired and demonstrate altered innervation to the organ of Corti, as well as fewer sensory hair cells. Furthermore, mouse embryonic stem cells become neuron-like when exposed to picomolar levels of MIF, suggesting the general importance of this cytokine in neural development.
Obesity improves myocardial ischaemic tolerance and RISK signalling in insulin-insensitive rats
Authors: Donner Daniel , Headrick John P. , Peart Jason N. , Du Toit Eugene F.
Published: November 2012

Obesity with associated metabolic disturbances worsens ischaemic heart disease outcomes, and rodent studies confirm that obesity with insulin-resistance impairs myocardial resistance to ischemia-reperfusion (I-R) injury. However, the effects of obesity per se are unclear, with some evidence for paradoxic cardioprotection (particularly in older subjects). We tested the impact of dietary obesity on I-R tolerance and reperfusion injury salvage kinase (RISK) signalling in hearts from middle-aged (10 months old) insulin-insensitive rats. Hearts from Wistar rats on either a 32-week control (CD) or high carbohydrate obesogenic (OB) diet were assessed for I-R resistance in vivo (45 minutes left anterior descending artery occlusion and 120 minutes reperfusion) and ex vivo (25 minutes ischemia and 60 minutes reperfusion). Expression and δ-opioid receptor (δ-OR) phospho-regulation of pro-survival (Akt/PKB, Erk1/2, eNOS) and pro-injury (GSK3β) enzymes were also examined. OB rats were heavier (764±25 versus 657±22 g for CD; P<0.05), hyperleptinaemic (11.1±0.7 versus 5.0±0.7 for CD; P<0.01) and comparably insulin-insensitive (HOMA-IR of 63.2±3.3 versus 63.2±1.6 for CD). In vivo infarction was more than halved in OB (20±3%) versus CD rats (45±6% P<0.05), as was post-ischaemic lactate dehydrogenase efflux (0.4±0.3 mU/ml versus 5.6±0.5 mU/ml; P<0.02) and ex vivo contractile dysfunction (62±2% versus 44±6% recovery of ventricular force; P<0.05). OB hearts exhibited up to 60% higher Akt expression, with increased phosphorylation of eNOS (+100%), GSK3β (+45%) and Erk1/2 (+15%). Pre-ischaemic δ-OR agonism with BW373U86 improved recoveries in CD hearts in association with phosphorylation of Akt (+40%), eNOS (+75%) and GSK3β (+30%), yet failed to further enhance RISK-NOS activation or I-R outcomes in OB hearts. In summary, dietary obesity in the context of age-related insulin-insensitivity paradoxically improves myocardial I-R tolerance, in association with moderate hyperleptinaemic and enhanced RISK expression and phospho-regulation. However, OB hearts are resistant to further RISK modulation and cardioprotection via acute δ-OR agonism.
Radiographic examination of the greater sciatic notch in determining the sex among Iranian people
Authors: Alizadeh Z , Hosseini A , Abkenari Sh Amani , Jabbari M
Published: November 2012

The distinctive morphology of the human innominate bone (os coxae) and its clear sexual dimorphism make it of interest from anatomical, anthropological and forensic points of view. The features of the greater sciatic notch of the coxae are characteristic and are commonly used to determine sex in unknown individuals. In this study, several measurements of the greater sciatic notch, e.g. width (AB), depth (OC) and width of the posterior segment (OB) were taken and indices I and II were calculated in 64 adult (32 men and 32 women) and side (right: left) coxae radiography (A-P view). Results indicated that out of all the parameters studied, width of the notch (right and left) ( P < 0.001), posterior segment width (right and left) ( P < 0.001), right ( P = 0.036) and left ( P = 0.008) index II of notch were found to be significantly greater in women as compared with men. Discriminant function analysis showed that the accuracy of sex determination varied from 100% in the men and 40% in the women groups to 70% for the total group. These results can be used as an aid to the identification of human skeletal remains in Iranian people.
Proton-conducting oxide and applications to hydrogen energy devices
Authors: Matsumoto Hiroshige , Sakai Takaaki , Okuyama Yuji
Published: November 2012

The change of the primary energy source from fossil fuels to the so-called renewable energies, such as solar and wind energy, is a major and necessary trend. The use of these energies needs efficient methods of energy storing and restoring, and hydrogen can serve for an effective conversion between the electricity and the chemical energy. This paper describes the ion-conducting materials applicable to the so-called “hydrogen energy system”. Since hydrogen works as an energy medium in this system, hydrogen-ion-transporting materials are beneficial. Proton-conducting oxides will work for this purpose and will be introduced here, viewing from material designing and working mechanism. Application of the proton-conducting oxide materials to water electrolysis is another topic, and how the materials work in principle for conversion between electricity and chemical energy and how their performances could/can be improved will be described.
"Dangerous fruit of the tree of knowledge": Mary Ann Evans, Emily Dickinson, and Strauss's Das Leben Jesu
Authors: Eberwein Jane Donahue
Published: November 2012

Dickinson's love for George Eliot's novels may have eased her anxieties caused by the Higher Criticism of the Bible which, emanating from Germany, unsettled faith in Victorian England and in her United States. Knowing that Mary Ann (Marian) Evans translated David Friedrich Strauss's Das Leben Jesu as a young woman, Dickinson might have felt more comfortable with reading the Bible in terms of mythology, comparative religion, and rhetorical/literary choices despite Strauss's challenge to historicist and literal interpretation. Comparison of Dickinson's poems on Nicodemus and on Jesus's conversation with the "good thief" demonstrate her ability to zero in on fundamental Christian messages while abandoning concerns with narrative context. In Adam Bede, The Mill on the Floss, Middlemarch , and other examples of Eliot's fiction, Dickinson would have found compassionate portrayals of struggling, suffering men and women whose faith experiences depended very little on theological sophistication. She might also have observed, in Eliot's representations of Casaubon and of Romola's father, their author's critique of intemperate scholarly zeal. Even if Dickinson knew little about Evans/ Eliot's own spiritual journey until Mathilde Blind's and J. W. Cross's accounts of her life appeared in 1883 and 1886, the poet's comments on this favorite novelist show sympathetic interest in a woman whose approach to religion differed from her own even though both dedicated themselves, in distinctive ways, to the "Art of Peace."