Regulation of chemokine receptor by Toll-like receptor 2 is critical to neutrophil migration and resistance to polymicrobial sepsis

Patients with sepsis have a marked defect in neutrophil migration. Here we identify a key role of Toll-like receptor 2 (TLR2) in the regulation of neutrophil migration and resistance during polymicrobial sepsis. We found that the expression of the chemokine receptor CXCR2 was dramatically down-regulated in circulating neutrophils from WT mice with severe sepsis, which correlates with reduced chemotaxis to CXCL2 in vitro and impaired migration into an infectious focus in vivo. TLR2 deficiency prevented the down-regulation of CXCR2 and failure of neutrophil migration. Moreover, TLR2(-/-) mice exhibited higher bacterial clearance, lower serum inflammatory cytokines, and improved survival rate during severe sepsis compared with WT mice. In vitro, the TLR2 agonist lipoteichoic acid (LTA) down-regulated CXCR2 expression and markedly inhibited the neutrophil chemotaxis and actin polymerization induced by CXCL2. Moreover, neutrophils activated ex vivo by LTA and adoptively transferred into naive WT recipient mice displayed a significantly reduced competence to migrate toward thioglycolate-induced peritonitis. Finally, LTA enhanced the expression of G protein-coupled receptor kinases 2 (GRK2) in neutrophils; increased expression of GRK2 was seen in blood neutrophils from WT mice, but not TLR2(-/-) mice, with severe sepsis. Our findings identify an unexpected detrimental role of TLR2 in polymicrobial sepsis and suggest that inhibition of TLR2 signaling may improve survival from sepsis.

Stage-specific integration of maternal and embryonic peroxisome proliferator-activated receptor delta signaling is critical to pregnancy success.

Successful pregnancy depends on well coordinated developmental events involving both maternal and embryonic components. Although a host of signaling pathways participate in implantation, decidualization, and placentation, whether there is a common molecular link that coordinates these processes remains unknown. By exploiting genetic, molecular, pharmacological, and physiological approaches, we show here that the nuclear transcription factor peroxisome proliferator-activated receptor (PPAR) delta plays a central role at various stages of pregnancy, whereas maternal PPARdelta is critical to implantation and decidualization, and embryonic PPARdelta is vital for placentation. Using trophoblast stem cells, we further elucidate that a reciprocal relationship between PPARdelta-AKT and leukemia inhibitory factor-STAT3 signaling pathways serves as a cell lineage sensor to direct trophoblast cell fates during placentation. This novel finding of stage-specific integration of maternal and embryonic PPARdelta signaling provides evidence that PPARdelta is a molecular link that coordinates implantation, decidualization, and placentation crucial to pregnancy success. This study is clinically relevant because deferral of on time implantation leads to spontaneous pregnancy loss, and defective trophoblast invasion is one cause of preeclampsia in humans.

Considerations on corrosion and weld repair effects on the fatigue strength of a steel structure critical to the flight-safety

The aim of this study is to analyze the effects of corrosion and successive tungsten inert gas (TIC) welding repairs on the reverse bending fatigue strength of AISI 4130 steel used in components critical to the flight-safety. The tests were performed on hot-rolled steel plate specimens, 1.10 mm and 1.60 mm thick, by means of a SCHENK PWS equipment, with load ratio R = -1, constant amplitude, 30 Hz frequency and room temperature. It was observed that the reverse bending fatigue strength of AISI 4130 steel decreases due to the corrosion and the TIC welding and re-welding processes. (C) 2010 Elsevier Ltd. All rights reserved.

Repair Welding Effects on the Bending Fatigue Strength of AISI 4130 Aeronautical Steel used in a Critical to the Flight-Safety Structure

The aim of this study was to analyze the effect of successive TIG (tungsten inert gas) welding repairs on the reverse bending fatigue strength of AISI 4130 steel, which is widely used in components critical to the flight-safety. In order to simulate the abrupt maneuvers, wind bursts, motor vibration and helixes efforts, which generate cyclic bending loadings at the welded joints of a specific aircraft component called motor cradle, experimental reverse bending fatigue tests were carried out on specimens made from hot-rolled steel plate, 1.10 mm (0.043 in) thick, by mean of a SCHENK PWS equipment, with load ratio R = -1, under constant amplitude, at 30 Hz frequency and room temperature. It was observed that the bending fatigue strength decreases after the TIG (Tungsten Inert Gas) welding process application on AISI 4130 steel, with subsequent decrease due to re-welding sequence as well. Microstructural analyses and microhardness measurements on the base material, heat-affected zone (HAZ) and weld metal, as well as the effects of the weld bead geometry on the obtained results, have complemented this study.

Considerations about the welding repair effects on the structural integrity of an airframe critical to the flight-safety

Structures critical to the flight-safety are commonly submitted to several maintenance repairs at the welded joints in order to prolong the in-service life of aircrafts. The aim of this study is to analyze the effects of Tungsten Inert Gas (TIG) welding repair on the structural integrity of the AISI 4130 aeronautical steel by means of experimental fatigue crack growth tests in base-material, heat-affected zone (HAZ) and weld metal. The tests were performed on hot-rolled steel plate specimens, 0.89 mm thick, with load ratio R = 0.1, constant amplitude, at 10 Hz frequency and room temperature. Increase of the fracture resistance was observed in the weld metal but decreasing in the HAZ after repair. The results were associated to microhardness and microstructural changes with the welding sequence. (C) 2010 Published by Elsevier Ltd.

Commentary: Dedication of Additional Resources to Evaluation and Low-Income Schools is Critical to Increasing Levels of Safe Walking and Bicycling to School

A commentary on Mendoza et al.'s article entitled, "Ethnic Minority Children’s Active Commuting to School and Association with Physical Activity and Pedestrian Safety Behaviors."

Emotions, Not Just Decision-Making Processes, Are Critical to an Evolutionary Model of Human Behavior

An evolutionary model of human behavior should privilege emotions: essential, phylogenetically ancient behaviors that learning and decision making only subserve. Infants and non-mammals lack advanced cognitive powers but still survive. Decision making is only a means to emotional ends, which organize and prioritize behavior. The emotion of pride/shame, or dominance striving, bridges the social and biological sciences via internalization of cultural norms.

Are team personality and climate related to satisfaction and software quality? Aggregating results from a twice replicated experiment

Research into software engineering teams focuses on human and social team factors. Social psychology deals with the study of team formation and has found that personality factors and group processes such as team climate are related to team effectiveness. However, there are only a handful of empirical studies dealing with personality and team climate and their relationship to software development team effectiveness. Objective We present aggregate results of a twice replicated quasi-experiment that evaluates the relationships between personality, team climate, product quality and satisfaction in software development teams. Method Our experimental study measures the personalities of team members based on the Big Five personality traits (openness, conscientiousness, extraversion, agreeableness, neuroticism) and team climate factors (participative safety, support for innovation, team vision and task orientation) preferences and perceptions. We aggregate the results of the three studies through a meta-analysis of correlations. The study was conducted with students. Results The aggregation of results from the baseline experiment and two replications corroborates the following findings. There is a positive relationship between all four climate factors and satisfaction in software development teams. Teams whose members score highest for the agreeableness personality factor have the highest satisfaction levels. The results unveil a significant positive correlation between the extraversion personality factor and software product quality. High participative safety and task orientation climate perceptions are significantly related to quality. Conclusions First, more efficient software development teams can be formed heeding personality factors like agreeableness and extraversion. Second, the team climate generated in software development teams should be monitored for team member satisfaction. Finally, aspects like people feeling safe giving their opinions or encouraging team members to work hard at their job can have an impact on software quality. Software project managers can take advantage of these factors to promote developer satisfaction and improve the resulting product.

Mutational analysis of NM23-H2/NDP kinase identifies the structural domains critical to recognition of a c-myc regulatory element.

NM23-H2, a presumed regulator of tumor metastasis in humans, is a hexameric protein with both enzymatic (NDP kinase) and regulatory (transcriptional activation) activity. While the structure and catalytic mechanisms have been well characterized, the mode of DNA binding is not known. We examined this latter function in a site-directed mutational study and identified residues and domains essential for the recognition of a c-myc regulatory sequence. Three amino acids, Arg-34, Asn-69, and Lys-135, were found among 30 possibilities to be critical for DNA binding. Two of these, Asn-69 and Lys-135, are not conserved between NM23 variants differing in DNA-binding potential, suggesting that DNA recognition resides partly in nonconserved amino acids. All three DNA-binding defective mutant proteins are active enzymatically and appear to be stable hexamers, suggesting that they perform at the level of DNA recognition and that separate functional domains exist for enzyme catalysis and DNA binding. In the context of the known crystal structure of NM23-H2, the DNA-binding residues are located within distinct structural motifs in the monomer, which are exposed to the surface near the 2-fold axis of adjacent subunits in the hexamer. These findings are explained by a model in which NM23-H2 binds DNA with a combinatorial surface consisting of the "outer" face of the dimer. Chemical crosslinking data support a dimeric DNA-binding mode by NM23-H2.

Prefaces biographical and critical, to the works of the english poets /

Mode of access: Internet.

Prefaces biographical and critical, to the works of the english poets /

Mode of access: Internet.

Prefaces biographical and critical, to the works of the english poets /

Mode of access: Internet.

Prefaces biographical and critical, to the works of the english poets /

Mode of access: Internet.

Prefaces biographical and critical, to the works of the english poets /

Mode of access: Internet.