gpDB: a database of GPCRs, G-proteins, effectors and their interactions

gpDB is a publicly accessible, relational database, containing information about G-proteins, G-protein coupled receptors (GPCRs) and effectors, as well as information concerning known interactions between these molecules. The sequences are classified according to a hierarchy of different classes, families and subfamilies based on literature search. The main innovation besides the classification of G-proteins, GPCRs and effectors is the relational model of the database, describing the known coupling specificity of GPCRs to their respective alpha subunits of G-proteins, and also the specific interaction between G-proteins and their effectors, a unique feature not available in any other database. AVAILABILITY: http://bioinformatics.biol.uoa.gr/gpDB CONTACT: shamodr@biol.uoa.gr SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.     

Pancreatic aplasia in a fetus with asplenia-cardiovascular defect-heterotaxy (Ivemark syndrome)

BACKGROUND: Asplenia or polysplenia and complex cardiovascular defects, in association with disturbed body symmetry and malposition of internal organs, constitute the main corpus of malformations in the heterogeneous group of heterotaxy disorders. In affected pregnancies, prenatal diagnosis is possible by ultrasonography, while prognosis and counseling largely depend upon the severity of the cardiac defect. CASE: We present a 25 week gestation fetus with typical findings of asplenia–cardiovascular defect–heterotaxy (Ivemark syndrome) and aplasia of the pancreas. CONCLUSIONS: Pancreatic aplasia emerges as an additional phenotypic feature in Ivemark syndrome and raises the possibility of total pancreatic insufficiency of the affected neonate as an additional, although rare, clinical consideration. Birth Defects Research (Part A) 2008. © 2008 Wiley‐Liss, Inc.     

Control of bone mass and remodeling by PTH receptor signaling in osteocytes

Osteocytes, former osteoblasts buried within bone, are thought to orchestrate skeletal adaptation to mechanical stimuli. However, it remains unknown whether hormones control skeletal homeostasis through actions on osteocytes. Parathyroid hormone (PTH) stimulates bone remodeling and may cause bone loss or bone gain depending on the balance between bone resorption and formation. Herein, we demonstrate that transgenic mice expressing a constitutively active PTH receptor exclusively in osteocytes exhibit increased bone mass and bone remodeling, as well as reduced expression of the osteocyte-derived Wnt antagonist sclerostin, increased Wnt signaling, increased osteoclast and osteoblast number, and decreased osteoblast apoptosis. Deletion of the Wnt co-receptor LDL related receptor 5 (LRP5) attenuates the high bone mass phenotype but not the increase in bone remodeling induced by the transgene. These findings demonstrate that PTH receptor signaling in osteocytes increases bone mass and the rate of bone remodeling through LRP5-dependent and -independent mechanisms, respectively.     

Inhibition of intestinal ischemia/repurfusion induced apoptosis and necrosis via down-regulation of the NF-kB, c-Jun and caspace-3 expression by epigallocatechin-3-gallate administration

Intestinal ischemia/reperfusion (I/R) produces reactive oxygen species (ROS) activating signal transduction and apoptosis. The aim of this study was to evaluate the effect of (-)-epigallocatechin-3-gallate (EGCG) administration in inhibition of apoptosis by attenuating the expression of NF-kB, c-Jun and caspace-3 in intestinal I/R. Thirty male wistar rats were used. Group A sham operation, B I/R, C I/R-EGCG 50 mg/kg ip. Intestinal ischemia was induced for 60 min by clamping the superior mesenteric artery. Malondialdehyde (MDA), myeloperoxidase (MPO), light histology, Fragment End Labelling of DNA (TUNEL), immunocytochemistry for NF-kB, c-Jun and caspace-3 analysis in intestinal specimens were performed 120 min after reperfusion. Apoptosis as indicated by TUNEL and Caspace-3, NF-kB and c-Jun was widely expressed in I/R group but only slightly expressed in EGCG treated groups. MDA and MPO showed a marked increase in the I/R group and a significant decrease in the EGCG treated group. Light histology showed preservation of architecture in the EGCG treated group. In conclusion, EGCG pre-treatment is likely to inhibit intestinal I/R-induced apoptosis by down-regulating the expression of NF-kB, c-Jun and caspase-3.     

Transduction of cell survival signals by connexin-43 hemichannels.

Bisphosphonates, drugs used widely in the treatment of bone diseases, prevent osteoblast and osteocyte apoptosis by a mechanism involving extracellular signal-regulated kinase (ERK) activation. We report herein that hexameric connexin (Cx)-43 hemichannels, but not gap junctions, are the essential transducers of the ERK-activating/anti-apoptotic effects of bisphosphonates. Transfection of Cx-43, but not other Cxs, into Cx-43 naive cells confers de novo responsiveness to the drugs. The signal-transducing property of Cx-43 requires the pore forming as well as the C-terminal domains of the protein, the activation of both Src and ERK kinases, and the SH2 and SH3 domains of Src. This evidence adds Cx-43 to the list of transmembrane proteins capable of transducing survival signals in response to extracellular cues and raises the possibility that it may serve in this capacity for endogenously produced molecules or even other drugs.     

Cradle-to-gate assessment of environmental impacts for a broad set of biomass-to-product process chains

Purpose

This study advocates a modular approach combining unit processes as building blocks to formulate biomass process chains. This approach facilitates a transparent environmental life cycle impact assessment for bio-based products. It also enhances the ability to develop and assess more complex biorefinery systems, identifies critical parameters and offers useful material to support environmental impact assessment in early design stages.

Methods

Twenty-three different products were assessed with regard to the environmental burden associated with their production paths. Life cycle inventories (LCIs) for 32 unit processes were compiled (using information from pilot plants, simulation and literature data) and organized in biomass process chains. Then, 58 study systems were formed based on various combinations of the unit processes, each study system referring to the production of a selected product. Three indicators were used for quantification of the impacts: non-renewable fossil cumulative energy demand (CED), global warming potential (GWP) and water depletion as defined in the ReCiPe method.

Results and discussion

Factors influencing the variation of results even for similar products are discussed (e.g. production path and allocation method lead to a range of GWP values for ethylene production from 0.43 to 3.37 kg CO₂ eq/kg ethylene). For the majority of bio-products, CED has lower values than fossil-based equivalents (average difference 39–70 MJ eq/kg product depending on the allocation method), while mixed trends are obtained for the GWP and water depletion indicators. Assessments also highlight attributes that have a significant effect in the environmental profile of a production path such as the synthesis path, the process chemistry (water intensity) and process-related factors (energy intensity, degree of energy integration/heat recovery).

Conclusions

The analysis of impacts per unit process is able to demonstrate the particular production stages featuring high environmental intensities along a path further hinting to suggestions for amendments and improvements from an overall performance perspective. The study makes a useful source for biorefinery design studies especially in adopting a modular approach to represent and to analyse biomass process chains; it also provides a reference point for comparison (benchmarking) between different process technologies for biomass utilization. Finally, the analysis is compatible with the standards of the LCA methodology, and it is based on the use of the most common LCA databases, which facilitates the comparison of the results with other relevant studies.

     

Research experience modifies how participants profit from journal clubs in academia

Because Journal Clubs (JClubs) represent valued educational tools, we often assume optimality of Journal Club practices. We analyze here JClubs records from a research group to identify factors that modify how much attendants benefit from discussing a paper. We demonstrate that attendants benefit most from papers focusing on systems similar to those they work on and that their ability to profit from different contribution types changes with research experience. Common JClubs practices such as the assignment of the paper selection to a single individual could thus compromise participant experience. Our conclusions may also be generalizable to situations outside academia.     

Influence of Intraaortic Balloon Pump Counterpulsation on Transesophageal Echocardiography Derived Determinants of Diastolic Function

Introduction

Intraaortic balloon pump counterpulsation (IABP) is often used in patients with acute coronary syndrome for its favourable effects on left ventricular (LV) systolic function and coronary perfusion. However, the effects of IABP on LV diastolic function have not been comprehensively investigated. Acute diastolic dysfunction has been linked to increased morbidity and mortality. The aim of this study was to examine the influence of IABP on LV diastolic dysfunction using standard TEE derived parameters.

Methods

Intraoperative TEE was performed in 10 patients (mean age 65 ± 11 yrs) undergoing urgent coronary artery bypass graft surgery (CABG), who had received an IABP preoperatively. TEE derived measures of diastolic dysfunction included early to late transmitral Doppler inflow velocity ratio (E/A), deceleration time (Dt), pulmonary venous systolic to diastolic Doppler velocity ratio (S/D), transmitral propagation velocity (Vp), and the ratio of early to late mitral annular tissue Doppler velocities (e’/a’). Statistical analyses included the Wilcoxon Sign-Rank test, and a p<0.05 was considered significant.

Results

Transmitral inflow E/A ratios increased significantly from 0.86 to 1.07 (p < 0.05), while Dt decreased significantly from 218 to 180 ms (p < 0.05) with the use of IABP. Significant increases in Vp (34 cm/s to 43 cm/s; p < 0.05), and e’/a’ (0.58 to 0.71; p < 0.05) suggested a favourable influence of intraaortic counterpulsation on diastolic function.

Conclusion

The use of perioperative IABP significantly improves TEE derived parameters of diastolic function consistent with a favourable impact on LV relaxation in cardiac surgery patients undergoing CABG.