bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract
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

Abstract

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

Abstract
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

Abstract

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

Abstract

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

Abstract
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

AbstractGenomics 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

AbstractChemical 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

Abstract
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

AbstractWe 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

Abstract
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

Abstract
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.