bluuebunny/crossref_metadata_2025_split huggingface dataset:
Talin-dependent integrin activation is required for fibrin clot retraction by platelets
Authors: Haling Jacob R. , Monkley Susan J. , Critchley David R. , Petrich Brian G. 
Published: October 2010

AbstractTalin functions both as a regulator of integrin affinity and as an important mechanical link between integrins and the cytoskeleton. Using genetic deletion of talin, we show for the first time that the capacity of talin to activate integrins is required for fibrin clot retraction by platelets. To further dissect which talin functions are required for this process, we tested clot retraction in platelets expressing a talin1(L325R) mutant that binds to integrins, but exhibits impaired integrin activation ascribable to disruption of the interaction between talin and the membrane-proximal region (MPR) in the β-integrin cytoplasmic domain. Talin-deficient and talin1(L325R) platelets were defective in retracting fibrin clots. However, the defect in clot retraction in talin1(L325R) platelets, but not talin-deficient platelets, was rescued by extrinsically activating integrins with manganese, thereby proving that integrin activation is required and showing that talin1(L325R) can form functional links to the actin cytoskeleton.
The complete mitochondrial genome of the citrus red mite Panonychus citri (Acari: Tetranychidae): high genome rearrangement and extremely truncated tRNAs
Authors: Yuan Ming-Long , Wei Dan-Dan , Wang Bao-Jun , Dou Wei , Wang Jin-Jun 
Published: October 2010

AbstractBackgroundThe family Tetranychidae (Chelicerata: Acari) includes ~1200 species, many of which are of agronomic importance. To date, mitochondrial genomes of only two Tetranychidae species have been sequenced, and it has been found that these two mitochondrial genomes are characterized by many unusual features in genome organization and structure such as gene order and nucleotide frequency. The scarcity of available sequence data has greatly impeded evolutionary studies in Acari (mites and ticks). Information on Tetranychidae mitochondrial genomes is quite important for phylogenetic evaluation and population genetics, as well as the molecular evolution of functional genes such as acaricide-resistance genes. In this study, we sequenced the complete mitochondrial genome ofPanonychus citri(Family Tetranychidae), a worldwide citrus pest, and provide a comparison to other Acari.ResultsThe mitochondrial genome ofP. citriis a typical circular molecule of 13,077 bp, and contains the complete set of 37 genes that are usually found in metazoans. This is the smallest mitochondrial genome within all sequenced Acari and other Chelicerata, primarily due to the significant size reduction of protein coding genes (PCGs), a large rRNA gene, and the A + T-rich region. The mitochondrial gene order forP. citriis the same as those forP. ulmiandTetranychus urticae, but distinctly different from other Acari by a series of gene translocations and/or inversions. The majority of theP. citrimitochondrial genome has a high A + T content (85.28%), which is also reflected by AT-rich codons being used more frequently, but exhibits a positive GC-skew (0.03). The Acari mitochondrialnad1exhibits a faster amino acid substitution rate than other genes, and the variation of nucleotide substitution patterns of PCGs is significantly correlated with the G + C content. Most tRNA genes ofP. citriare extremely truncated and atypical (44-65, 54.1 ± 4.1 bp), lacking either the T- or D-arm, as found inP. ulmi,T. urticae, and other Acariform mites.ConclusionsTheP. citrimitochondrial gene order is markedly different from those of other chelicerates, but is conserved within the family Tetranychidae indicating that high rearrangements have occurred after Tetranychidae diverged from other Acari. Comparative analyses suggest that the genome size, gene order, gene content, codon usage, and base composition are strongly variable among Acari mitochondrial genomes. While extremely small and unusual tRNA genes seem to be common for Acariform mites, further experimental evidence is needed.
Explaining the impact of a women's group led community mobilisation intervention on maternal and newborn health outcomes: the Ekjut trial process evaluation
Authors: Rath Suchitra , Nair Nirmala , Tripathy Prasanta K , Barnett Sarah , Rath Shibanand , Mahapatra Rajendra , Gope Rajkumar , Bajpai Aparna , Sinha Rajesh , Costello Anthony , Prost Audrey 
Published: October 2010

Abstract

Background
Few large and rigorous evaluations of participatory interventions systematically describe their context and implementation, or attempt to explain the mechanisms behind their impact. This study reports process evaluation data from the Ekjut cluster-randomised controlled trial of a participatory learning and action cycle with women's groups to improve maternal and newborn health outcomes in Jharkhand and Orissa, eastern India (2005-2008). The study demonstrated a 45% reduction in neonatal mortality in the last two years of the intervention, largely driven by improvements in safe practices for home deliveries.

Methods
A participatory learning and action cycle with 244 women's groups was implemented in 18 intervention clusters covering an estimated population of 114 141. We describe the context, content, and implementation of this intervention, identify potential mechanisms behind its impact, and report challenges experienced in the field. Methods included a review of intervention documents, qualitative structured discussions with group members and non-group members, meeting observations, as well as descriptive statistical analysis of data on meeting attendance, activities, and characteristics of group attendees.

Results
Six broad, interrelated factors influenced the intervention's impact: (1) acceptability; (2) a participatory approach to the development of knowledge, skills and 'critical consciousness'; (3) community involvement beyond the groups; (4) a focus on marginalized communities; (5) the active recruitment of newly pregnant women into groups; (6) high population coverage. We hypothesize that these factors were responsible for the increase in safe delivery and care practices that led to the reduction in neonatal mortality demonstrated in the Ekjut trial.

Conclusions
Participatory interventions with community groups can influence maternal and child health outcomes if key intervention characteristics are preserved and tailored to local contexts. Scaling-up such interventions requires (1) a detailed understanding of the way in which context affects the acceptability and delivery of the intervention; (2) planned but flexible replication of key content and implementation features; (3) strong support for participatory methods from implementing agencies.
EGFR inhibitor C225 increases the radiosensitivity of human lung squamous cancer cells
Authors: Zhang Yingdong , Wang Junjie , Liu Feng , You Zhenyu , Yang Ruijie , Zhao Yong 
Published: October 2010

AbstractBackgroundThe purpose of the present study is to investigate the direct biological effects of the epidermal growth factor receptor (EGFR) inhibitor C225 on the radiosensitivity of human lung squamous cancer cell-H520. H520 cells were treated with different dosage of60Co γ ray irradiation (1.953 Gy/min) in the presence or absence of C225. The cellular proliferation, colony forming capacity, apoptosis, the cell cycle distribution as well as caspase-3 were analyzed in vitro.ResultsWe found that C225 treatment significantly increased radiosensitivity of H-520 cells to irradiation, and led to cell cycle arrest in G1phase, whereas60Co γ ray irradiation mainly caused G2phase arrest. H-520 cells thus displayed both the G1and G2phase arrest upon treatment with C225 in combination with60Co γ ray irradiation. Moreover, C225 treatment significantly increased the apoptosis percentage of H-520 cells (13.91% ± 1.88%) compared with the control group (5.75% ± 0.64%, P < 0.05).ConclusionIn this regard, C225 treatment may make H-520 cells more sensitive to irradiation through the enhancement of caspase-3 mediated tumor cell apoptosis and cell cycle arrest.
Results of a sector-wide quality improvement initiative for substance-abuse care: an uncontrolled before-after study in Catalonia, Spain
Authors: Hilarion Pilar , Groene Oliver , Colom Joan , Lopez Rosa M , Suñol Rosa 
Published: October 2010

Abstract

Background
The Health Department of the Regional Government of Catalonia, Spain, issued a quality plan for substance abuse centers. The objective of this paper is to evaluate the impact of a multidimensional quality improvement initiative in the field of substance abuse care and to discuss potentials and limitations for further quality improvement.

Methods
The study uses an uncontrolled, sector-wide pre-post design. All centers providing services for persons with substance abuse issues in the Autonomous Community of Catalonia participated in this assessment. Measures of compliance were developed based on indicators reported in the literature and by broad stakeholder involvement. We compared pre-post differences in dimension-specific and overall compliance-scores using one-way ANOVA for repeated measures and the Friedman statistic. We described the spread of the data using the inter-quartile range and the Fligner-Killen statistic. Finally, we adjusted compliance scores for location and size using linear and logistic regression models.

Results
We performed a baseline and follow up assessment in 22 centers for substance abuse care and observed substantial and statistically significant improvements for overall compliance (pre: 60.9%; post: 79.1%) and for compliance in the dimensions 'care pathway' (pre: 66.5%; post: 83.5%) and 'organization and management' (pre: 50.5%; post: 77.2%). We observed improvements in the dimension 'environment and infrastructure' (pre: 81.8%; post: 95.5%) and in the dimension 'relations and user rights' (pre: 66.5%; post: 72.5%); however, these were not statistically significant. The regression analysis suggests that improvements in compliance are positively influenced by being located in the Barcelona region in case of the dimension 'relations and user rights'.

Conclusion
The positive results of this quality improvement initiative are possibly associated with the successful involvement of stakeholders, the consciously constructed feedback reports on individual and sector-wide performance and the support of evidence-based guidance wherever possible. Further research should address how contextual issues shape the uptake and effectiveness of quality improvement actions and how such quality improvements can be sustained.
Store-operated Ca2+ signaling in dendritic cells occurs independently of STIM1
Authors: Bandyopadhyay Bidhan C , Pingle Sandeep C , Ahern Gerard P 
Published: October 2010

ABSTRACTSOCE via CRAC channels is a critical signaling event in immune cells. Recent studies have identified key proteins underlying this process; STIM is an ER Ca2+ sensor that interacts with Orai, an intrinsic, pore-forming protein of the CRAC channel. In heterologous expression systems, STIM1 regulates SOCE by interacting with Orai1, -2, and -3. In native tissues, however, the precise roles of STIM and Orai proteins are not well defined. Here, we have investigated the molecular components of SOCE signaling in mouse DCs. We show that DCs predominantly express STIM2 and only very low levels of STIM1 compared with T lymphocytes. Upon store depletion with Tg, STIM2 aggregates and interacts selectively with Orai2. In contrast, Tg fails to aggregate STIM1 or enhance STIM1-mediated interactions with Orai proteins. Consistent with this biochemical characterization, stimulation of DCs with the adhesion molecule ICAM-1 selectively recruits STIM2 and Orai2 to the IS. Together, these data demonstrate a novel, STIM2-dependent SOCE signaling pathway in DCs.
Peroxisome-Generated Hydrogen Peroxide as Important Mediator of Lipotoxicity in Insulin-Producing Cells
Authors: Elsner Matthias , Gehrmann Wiebke , Lenzen Sigurd 
Published: October 2010

OBJECTIVE
Type 2 diabetes is a complex disease that is accompanied by elevated levels of nonesterified fatty acids (NEFAs), which contribute to β-cell dysfunction and β-cell loss, referred to as lipotoxicity. Experimental evidence suggests that oxidative stress is involved in lipotoxicity. In this study, we analyzed the molecular mechanisms of reactive oxygen species-mediated lipotoxicity in insulin-producing RINm5F cells and INS-1E cells as well as in primary rat islet cells.

RESEARCH DESIGN AND METHODS
The toxicity of saturated NEFAs with different chain lengths upon insulin-producing cells was determined by MTT and propidium iodide (PI) viability assays. Catalase or superoxide dismutase overexpressing cells were used to analyze the nature and the cellular compartment of reactive oxygen species formation. With the new H2O2-sensitive fluorescent protein HyPer H2O2 formation induced by exposure to palmitic acid was determined.

RESULTS
Only long-chain (&gt;C14) saturated NEFAs were toxic to insulin-producing cells. Overexpression of catalase in the peroxisomes and in the cytosol, but not in the mitochondria, significantly reduced H2O2 formation and protected the cells against palmitic acid-induced toxicity. With the HyPer protein, H2O2 generation was directly detectable in the peroxisomes of RINm5F and INS-1E insulin-producing cells as well as in primary rat islet cells.

CONCLUSIONS
The results demonstrate that H2O2 formation in the peroxisomes rather than in the mitochondria are responsible for NEFA-induced toxicity. Therefore, we propose a new concept of fatty acid-induced β-cell lipotoxicity mediated via reactive oxygen species formation through peroxisomal β- oxidation.
P-Selectin Glycoprotein Ligand-1 Deficiency Is Protective Against Obesity-Related Insulin Resistance
Authors: Sato Chikage , Shikata Kenichi , Hirota Daisho , Sasaki Motofumi , Nishishita Shingo , Miyamoto Satoshi , Kodera Ryo , Ogawa Daisuke , Tone Atsuhito , Kataoka Hitomi Usui , Wada Jun , Kajitani Nobuo , Makino Hirofumi 
Published: October 2010

OBJECTIVE
An inflammatory process is involved in the mechanism of obesity-related insulin resistance. Recent studies indicate that monocyte chemoattractant protein-1 (MCP-1) is a major chemokine that promotes monocyte infiltration into adipose tissues; however, the adhesion pathway in adipose tissues remains unclear. We aimed to clarify the adhesion molecules that mediate monocyte infiltration into adipose tissue.

RESEARCH DESIGN AND METHODS
We used a DNA microarray to compare the gene expression profiles in epididymal white adipose tissues (eWAT) between db/db mice and C57/BL6 mice each fed a high-fat diet (HFD) or a low-fat diet (LFD). We investigated the change of insulin resistance and inflammation in eWAT in P-selectin glycoprotein ligand-1 (PSGL-1) homozygous knockout (PSGL-1−/−) mice compared with wild-type (WT) mice fed HFD.

RESULTS
DNA microarray analysis revealed that PSGL-1, a major ligand for selectins, is upregulated in eWAT from both db/db mice and WT mice fed HFD. Quantitative real-time RT-PCR and immunohistochemistry showed that PSGL-1 is expressed on both endothelial cells and macrophages in eWAT of obese mice. PSGL-1−/− mice fed HFD showed a remarkable reduction of macrophage accumulation and expression of proinflammatory genes, including MCP-1 in eWAT. Moreover, adipocyte hypertrophy, insulin resistance, lipid metabolism, and hepatic fatty change were improved in PSGL-1−/− mice compared with WT mice fed HFD.

CONCLUSIONS
These results indicate that PSGL-1 is a crucial adhesion molecule for the recruitment of monocytes into adipose tissues in obese mice, making it a candidate for a novel therapeutic target for the prevention of obesity-related insulin resistance.
Production of Functional Glucagon-Secreting α-Cells From Human Embryonic Stem Cells
Authors: Rezania Alireza , Riedel Michael J. , Wideman Rhonda D. , Karanu Francis , Ao Ziliang , Warnock Garth L. , Kieffer Timothy J. 
Published: October 2010

OBJECTIVE
Differentiation of human embryonic stem (hES) cells to fully developed cell types holds great therapeutic promise. Despite significant progress, the conversion of hES cells to stable, fully differentiated endocrine cells that exhibit physiologically regulated hormone secretion has not yet been achieved. Here we describe an efficient differentiation protocol for the in vitro conversion of hES cells to functional glucagon-producing α- cells.

RESEARCH DESIGN AND METHODS
Using a combination of small molecule screening and empirical testing, we developed a six-stage differentiation protocol for creating functional α-cells. An extensive in vitro and in vivo characterization of the differentiated cells was performed.

RESULTS
A high rate of synaptophysin expression (&gt;75%) and robust expression of glucagon and the α-cell transcription factor ARX was achieved. After a transient polyhormonal state in which cells coexpress glucagon and insulin, maturation in vitro or in vivo resulted in depletion of insulin and other β-cell markers with concomitant enrichment of α-cell markers. After transplantation, these cells secreted fully processed, biologically active glucagon in response to physiologic stimuli including prolonged fasting and amino acid challenge. Moreover, glucagon release from transplanted cells was sufficient to reduce demand for pancreatic glucagon, resulting in a significant decrease in pancreatic α-cell mass.

CONCLUSIONS
These results indicate that fully differentiated pancreatic endocrine cells can be created via stepwise differentiation of hES cells. These cells may serve as a useful screening tool for the identification of compounds that modulate glucagon secretion as well as those that promote the transdifferentiation of α-cells to β-cells.
The effect of soil surfactants on soil hydrological behavior, the plant growth environment, irrigation efficiency and water conservation
Authors: Moore Demie , Kostka Stanley , Boerth Thomas , Franklin Mica , Ritsema Coen , Dekker Louis , Oostindie Klaas , Stoof Cathelijne , Wesseling Jan 
Published: October 2010

The effect of soil surfactants on soil hydrological behavior, the plant growth environment, irrigation efficiency and water conservationSoil water repellency causes at least temporal changes in the hydrological properties of a soil which result in, among other things, suboptimal growing conditions and increased irrigation requirements. Water repellency in soil is more widespread than previously thought and has been identified in many soil types under a wide array of climatic conditions worldwide. Consequences of soil water repellency include loss of wettability, increased runoff and preferential flow, reduced access to water for plants, reduced irrigation efficiency, increased requirement for water and other inputs, and increased potential for non-point source pollution. Research indicates that certain soil surfactants can be used to manage soil water repellency by modifying the flow dynamics of water and restoring soil wettability. This results in improved hydrological behavior of those soils. Consequently, the plant growth environment is also improved and significant water conservation is possible through more efficient functioning of the soil.
Improvement performance of Al-Wathba settling tank by a computational fluid dynamics model
Authors: Kriš Jozef , Hadi Ghawi 
Published: October 2010

Improvement performance of Al-Wathba settling tank by a computational fluid dynamics modelAn investigation has been carried out using the FLUENT Computational Fluid Dynamics (CFD) software, which uses the finite-volume method to determine whether it is feasible to improve the capacity and quality of the clarifier at the Al-Wathba Water Treatment Works (Iraq) by some relatively inexpensive means. Simulations were carried out with two dimensional, radially symmetric models, representing the existing configuration as well as a number of proposed modifications involving baffles and additional clarified water off-takes. A convection-diffusion equation, which is extended to incorporate the sedimentation of sludge flocs in the field of gravity, governs the mass transfer in the clarifier. The standardk-ε turbulence model is used to compute the turbulent motion, and our CFD model accounts for buoyancy flow. The sludge settling velocity was measured as a function of the concentration, and we have used the double-exponential settling velocity function to describe its dependence on the concentration. The CFD model is validated using measured concentration profiles. The results were evaluated on the basis of the simulated profiles of vertical up-flow velocity in the body of the clarifier.
Editorial
Authors: Mach Mojmír 
Published: October 2010

Editorial
Communication - Dialogue - Co-operation - Solving problems. These are the words of nowadays Europe. Such approaches should be used in broad spectrum of life as well as in toxicology. It is therefore admirable that EUROTOX commissars, mainly past-president Prof. Liesivuori, invited all heads of European toxicological societies to discuss current issues of toxicology in Europe during IUTOX meeting held in Barcelona in July 2010. Renowned scientists and regulatory officers from Government, Industry and Academia made appearance and talked about contribution of toxicological research to society, importance of communication and education. The strategic meeting was successful. Prof. Liesivuori expressed gratitude to all delegates for the great suggestions and key findings resulting from the brainstorming sessions conducted during the meeting. Majority of delegates agreed that education in toxicology and related fields is the top priority for future. Communication towards society, in the sense of explaining possible risks, should be an important concern as well. Taking a good example from EUROTOX, on the verge of summer the Slovak Toxicology Society SETOX organizes meeting of the toxicological societies from the Central Europe, i.e. Slovak, Czech, Polish, Austrian and Hungarian societies of toxicology. First positive step was done by Visegrad Fund and Federation of European Toxicologists & European Societies of Toxicology, which supported this meeting. It is essential for successful co-operation to establish strong connections, which can be further crucial for meaningful and highly profitable information to society.
Importance of molecular cell biology investigations in human medicine in the story of the Hutchinson-Gilford progeria syndrome
Authors: Raška Ivan 
Published: October 2010

Importance of molecular cell biology investigations in human medicine in the story of the Hutchinson-Gilford progeria syndromeRanged among laminopathies, Hutchinson-Gilford progeria syndrome is a syndrome that involves premature aging, leading usually to death at the age between 10 to 14 years predominatly due to a myocardial infarction or a stroke. In the lecture I shall overview the importance of molecular cell biology investigations that led to the discovery of the basic mechanism standing behind this rare syndrome. The genetic basis in most cases is a mutation at the nucleotide position 1824 of the lamin A gene. At this position, cytosine is substituted for thymine so that a cryptic splice site within the precursor mRNA for lamin A is generated. This results in a production of abnormal lamin A, termed progerin, its presence in cells having a deleterious dominant effect. Depending on the cell type and tissue, progerin induces a pleiotropy of defects that vary in different tissues. The present endeavour how to challenge this terrible disease will be also mentioned.