bluuebunny/crossref_metadata_2025 huggingface dataset:
Melittin prevents liver cancer cell metastasis through inhibition of the Rac1-dependent pathway
Authors: Liu Shujing , Yu Mei , He Ying , Xiao Lin , Wang Fang , Song Changcheng , Sun Shuhan , Ling Changquan , Xu Zhiheng
Published: February 2008

Melittin, a water-soluble toxic peptide derived from bee venom of

Apis mellifera

was reported to have inhibitory effects on hepatocellular carcinoma (HCC). However, its role in antimetastasis and the underlying mechanism remains elusive. By utilizing both HCC cell lines and an animal model based assay system, we found that Rac1, which has been shown to be involved in cancer cell metastasis, is highly expressed in aggressive HCC cell lines and its activity correlated with cell motility and cytoskeleton polymerization. In addition, Rac1-dependent activity and metastatic potential of aggressive HCC cells are remarkably high in both cellular and nude mouse models. We provide evidence here that melittin inhibits the viability and motility of HCC cells

in vitro

, which correlates with its suppression of Rac1-dependent activity, cell motility, and microfilament depolymerization. Furthermore, melittin suppresses both HCC metastasis and Rac1-dependent activity in nude mouse models. The specificity of the effect of melittin on Rac1 was confirmed in HCC cells both

in vitro

and

in vivo.

Conclusion:

Melittin inhibits tumor cell metastasis by reducing cell motility and migration via the suppression of Rac1-dependent pathway, suggesting that melittin is a potential therapeutic agent for HCC.
Metron factor-1 prevents liver injury without promoting tumor growth and metastasis
Authors: Takahara Terumi , Xue Feng , Mazzone Massimiliano , Yata Yutaka , Nonome Kazunobu , Kanayama Masami , Kawai Kengo , Pisacane Alberto M. , Takahara Shiro , Li Xiao-Kang , Comoglio Paolo M. , Sugiyama Toshiro , Michieli Paolo
Published: February 2008

Hepatocyte growth factor (HGF) is the most powerful hepatotrophic factor identified so far. However, the ability of HGF to promote tumor cell “scattering” and invasion raises some concern about its therapeutic safety. We compared the therapeutic efficacy of HGF with that of Metron Factor-1 (MF-1), an engineered cytokine derived from HGF and the HGF-like factor macrophage stimulating protein (MSP), in mouse models of acute and chronic liver injury. At the same time, we tested the ability of HGF and MF-1 to promote tumor growth, angiogenesis, and invasion in several mouse models of cancer. We show that (1) MF-1 and HGF stimulate hepatocyte proliferation

in vitro

; (2) MF-1 and HGF protect primary hepatocytes against Fas-induced and drug-induced apoptosis; (3) HGF but not MF-1 induces scattering and matrigel invasion of carcinoma cell lines

in vitro

; (4) HGF but not MF-1 promotes migration and extracellular matrix invasion of endothelial cells

in vitro

; (5) MF-1 and HGF prevent CCl4-induced acute liver injury as measured by alanine aminotransferase (ALT) levels, histology, terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) analysis, and phospho-histone-3 immunostaining; (6) MF-1 and HGF attenuate liver fibrosis caused by chronic CCl4 intoxication and promote regeneration as measured by Sirius red staining, alpha-smooth muscle actin immunostaining, and Ki-67 analysis; (7) HGF but not MF-1 promotes tumor growth, angiogenesis, and metastasis in a variety of xenograft models; (8) HGF but not MF-1 promotes intrahepatic dissemination of hepatocarcinoma cells injected orthotopically.

Conclusion:

These data suggest that MF-1 is as effective as HGF at preventing liver injury and at promoting hepatocyte regeneration, but therapeutically safer than HGF because it lacks proangiogenic and prometastatic activity.
Relationship between daily dose of oral medications and idiosyncratic drug-induced liver injury: Search for signals
Authors: Lammert Craig , Einarsson Stefan , Saha Chandan , Niklasson Anna , Bjornsson Einar , Chalasani Naga
Published: February 2008

Idiosyncratic drug-induced liver injury (DILI) is traditionally thought not to be dose-related. However, it has been pointed out that most medicines that were withdrawn from marketing or received a black-box warning because of hepatotoxicity were prescribed at daily doses greater than 50 mg/day. To examine the relationship between daily dose of medications and idiosyncratic DILI, we conducted a study with two aims. First, using two pharmaceutical databases, we examined the relationship between daily dose of commonly prescribed medicines in the United States and reported frequency of their selected hepatic adverse events. Second, we examined serious DILI cases reported to the Swedish Adverse Drug Reactions Advisory Committee (1970-2004) for any signals supporting the relationship between daily dose and idiosyncratic DILI. Medications were categorized into ≤10 mg/day, 11-49 mg/day, and ≥50 mg/day groups. Among US prescription medicines, a statistically significant relationship was observed between daily dose of oral medicines and reports of liver failure (

P

= 0.009), liver transplantation (

P

< 0.001), and death caused by DILI (

P

= 0.004) but not alanine aminotransferase (ALT) > 3 × upper limit of normal (

P

= 0.10) or jaundice (

P

= 0.16). Of 598 eligible Swedish DILI cases, 9% belonged to the ≤10 mg/day group, 14.2% to the 11-49 mg/day group, and 77% of cases were caused by medications given at dose ≥50 mg/day. A statistically significant relationship was noted between daily dose and poor outcome (death or liver transplantation) of Swedish DILI cases (2%, 9.4%, and 13.2% in ≤10, 11-49, and ≥50 mg/day groups, respectively,

P

= 0.03).

Conclusion:

These data suggest a relationship between daily doses of oral prescription medications and idiosyncratic DILI. More studies are needed to validate these observations and to explore their implications.
Enhancement of nanofibrous scaffold of multiwalled carbon nanotubes/polyurethane composite to the fibroblasts growth and biosynthesis
Authors: Meng Jie , Kong Hua , Han Zhaozhao , Wang Chaoying , Zhu Guangjin , Xie Sishen , Xu Haiyan
Published: February 2008

In this work, the effect of nanofibrous structure and multiwalled carbon nanotubes (MWNTs) incorporation in the polyurethane (PU) on the fibroblasts growth behavior was studied. The nanofibrous scaffold of multiwalled carbon nanotubes and polyurethane composite (MWNT/PU) with an average fiber diameter of 300–500 nm was fabricated by electrospinning technique. The nanofibrous scaffold of PU, smooth film of PU, and MWNT/PU were also prepared as controls. Cell viability assay, laser confocal microscopy, and scanning electron microscopy were applied to evaluate cell adhesion, proliferation, and cytoskeletal development on the scaffolds, respectively. Cell‐released protein was analyzed by Bradford protein assay, sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE), mass spectrometry, and transwell assay, respectively. Experimental results demonstrated that the scaffold with nanofibrous structure and MWNTs incorporation exhibited highest enhancement not only to the cell adhesion and proliferation but also to the cell migration and aggregation. Besides, cells cultured on the nanofibrous scaffold of MWNT/PU released the largest amount of proteins including collagen in comparison with those on the other substrates. Hence, the nanofibrous architecture and MWNTs incorporation provided favorite interactions to the cells, which implied the application potentials of the nanofibrous composite for tissue repair and regeneration. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Surface patterning of poly(L‐lactide) upon melt processing: In vitro culturing of fibroblasts and osteoblasts on surfaces ranging from highly crystalline with spherulitic protrusions to amorphous with nanoscale indentations
Authors: Degirmenbasi Nebahat , Ozkan Seher , Kalyon Dilhan M. , Yu Xiaojun
Published: February 2008

Large‐scale and reproducible manufacturing of scaffolds for tissue engineering applications will necessitate the adoption of methods relying on the processing of the biodegradable polymers directly from the melt. Such solventless processing will give rise to bulk and surface properties that will differ significantly from those generated upon processing from solution‐based methods. Thus, detailed understanding of the microstructures that are developed during melt processing and the resulting surface/cell interactions is needed. Here, surfaces of melt‐cast poly(L‐lactide) (PLLA) were patterned to furnish membrane samples with a wide range of crystallinity and significant differences in surface topographies, ranging from highly crystalline (60%) with spherulitic protrusions at the surface to amorphous with nanoscale indentations. The PLLA membranes were used to culture in vitro mouse 3T3‐Swiss albino fibroblast cells and osteoblast‐like MC3T3‐E1 cells. The growth rates of 3T3 fibroblasts were significantly lower on highly crystalline PLLA membranes with spherulitic protrusions in comparison to crystalline PLLA without spherulitic protrusions and amorphous surfaces with 5–10‐nm‐deep indentations. However, the differences in the growth rates of osteoblast‐like cells cultured on the PLLA membranes with different surface patterns were only marginally different. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
A computational strategy for thermo‐poroelastic structures with a time–space interface coupling
Authors: Néron D. , Dureisseix D.
Published: February 2008

This paper deals with a computational strategy suitable for the simulation of multiphysics problems, based on the large time increment (LATIN) method. The simulation of such problems must encounter the possible different time and space scales that usually arise with the different physics. Herein, we focus on using different time and space discretizations for each physics by introducing an interface with its own discretization. The feasibility of both time and space couplings is exemplified on a non‐linear 3‐physics strongly coupled problem: the thermal/fluid/structure interaction in a thermo‐poroelastic structure. Copyright © 2008 John Wiley & Sons, Ltd.
Stage 1 testing and pharmacodynamic evaluation of the HSP90 inhibitor alvespimycin (17‐DMAG, KOS‐1022) by the pediatric preclinical testing program
Authors: Smith Malcolm A. , Morton Christopher L. , Phelps Doris A. , Kolb E. Anders , Lock Richard , Carol Hernan , Reynolds C. Patrick , Maris John M. , Keir Stephen T. , Wu Jianrong , Houghton Peter J.
Published: February 2008

Background

Alvespimycin (17‐DMAG, KOS‐1022), a potent small‐molecule inhibitor of the protein chaperone Hsp90, is being developed as an anticancer agent because of the multiple Hsp90 client proteins involved in cancer cell growth and survival.

Procedures

Alvespimycin was tested against the in vitro panel of the Pediatric Preclinical Testing Program (PPTP) at concentrations from 1 nM to 10 µM and was tested against the PPTP's in vivo tumor panels by intraperitoneal administration using a 50 mg/kg BID twice weekly × 6 weeks dose and schedule. Hsp70 induction in tumor and liver tissue was used as a pharmacodynamic measure of Hsp90 inhibition and stress response induction.

Results

Alvespimycin had a median IC50 of 68 nM against the PPTP's in vitro panel, with a trend for lower IC50 values for the rhabdomyosarcoma panel (median IC50 32 nM) and for higher IC50 values for the neuroblastoma panel (median IC50 380 nM). Using the time to event activity measure, alvespimycin had intermediate or high activity against 4 of 28 evaluable solid tumor xenografts, including 3 of 4 alveolar rhabdomyosarcoma xenografts (one with a partial response). Hsp70 induction was observed in tumor tissue from both responding and non‐responding xenografts.

Conclusions

Alvespimycin demonstrated little in vivo antitumor activity against most of the PPTP's preclinical models. The greatest drug effect was observed for the alveolar rhabdomyosarcoma xenografts in the rhabdomyosarcoma panel. Hsp70 induction was observed in responding and non‐responding xenografts, suggesting that tumor‐specific events subsequent to HSP90 inhibition are primary determinants of antitumor activity. Pediatr Blood Cancer 2008;51:34–41. © 2008 Wiley‐Liss, Inc.
Dielectric studies of water absorption and desorption in epoxy resins: influence of cure process on behaviour
Authors: McConnell Barry K , Pethrick Richard A
Published: February 2008

Little is known about the way in which the chemical structure of an epoxy resin influences its ability to absorb and desorb moisture. This issue is addressed in a study of dicyandiamide‐ and amine‐cured epoxy resins. The dicyandiamide‐cured material will have a significantly lower preponderance of pendant hydroxyl groups than the amine‐cured material and may exhibit different behaviour when exposed to moisture. The uptake and loss of moisture was monitored gravimetrically, using broad band dielectric, dynamic mechanical thermal analysis and thickness measurements performed as a function of time at various temperatures. A comparison of the uptake and loss profiles for the first and subsequent cycles indicated significant differences in behaviour attributed to the way in which water can plasticise the matrix. Stresses frozen into the matrix during the cure process are allowed to relax as a consequence of the water hydrating the matrix and create voids and also allow matrix densification. These processes occur during the first hydration cycle and are not reversible. Subsequent hydration and dehydration appear to be reversible after the first hydration cycle. Water in the polymer is distributed between free water which is to be found in microvoids and bound water which is attached to the polymer chain. The amine‐cured epoxy resin which contains pendant hydroxyl groups has a greater capacity for water absorption than the ether‐containing backbone of the dicyandiamide‐cured material. Copyright © 2008 Society of Chemical Industry
Primhe: Primary Care Mental Health & Education
Authors: White Tony
Published: February 2008

The role of the primary care liaison nurse

Here, Tony White provides an overview of the key responsibilities of primary care liaison nurses (PCLNs), the impact they can have on the management of mental illness in primary care and the potential difficulties they currently face. Copyright © 2008 Wiley Interface Ltd
Experimental study of plasmonically enhanced GaN nanowire light emitters
Authors: Mastro Michael A. , Freitas Jaime A. , Twigg Mark , Holm R. T. , Eddy Charles R. , Kub Fritz , Kim Hong‐Yeol , Ahn Jaehui , Kim Jihyun
Published: February 2008

Plasmonic‐enhanced emission was achieved from a III‐nitride nano‐wire optoelectronic device. The III‐nitride system has been widely applied to light emitters in the blue, violet and ultra‐violet portions of the electromagnetic spectrum. One limit to its application has been the efficiency reduction associated with the inherently defective nature (particularly threading dislocations) of the material that is typically grown by hetero‐epitaxy. The VLS fabrication technique inherently yields defect‐free material that serves as an excellent emission and gain media. A two‐step approach was developed in a metalorganic chemical vapor deposition system to grow nano‐wires initially vertically by the VLS mechanism and, when necessary, laterally by altering the growth conditions. Furthermore, various silver coatings were employed to enhance the plasmonic‐based transfer of electromagnetic energy generated in the nano‐wire to the external near‐field. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Elastic properties of the fcc crystals of soft spheres with size dispersion at zero temperature
Authors: Narojczyk J. W. , Wojciechowski K. W.
Published: February 2008

Elastic constants of soft sphere systems, interacting through n ‐inverse‐power potential and exhibiting aperiodicity, caused by the size dispersion of the spheres, are determined at zero temperature by computer simulations. It is shown that, at a fixed number density of the spheres, the Poisson's ratio, as well as other elastic constants, increase with increasing disorder in the system. Properties of two types of systems, polydisperse spheres and binary mixture of spheres, are compared to determine the influence of various size distribution types on the system elastic properties. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A mass spectrometric method to simultaneously measure a biomarker and dilution marker in exhaled breath condensate
Authors: Esther Charles R. , Jasin H. Matias , Collins Leonard B. , Swenberg James A. , Boysen Gunnar
Published: February 2008

Exhaled breath condensate (EBC) collection is a simple and non‐invasive method to sample airway secretions, but analysis is limited by extensive and variable dilution of airway secretions within the condensate. To overcome this limitation, we developed a sensitive and specific liquid chromatography/tandem mass spectrometry (LC/MS/MS) method to simultaneously detect adenyl purines as biomarkers of inflammation and urea as a dilution marker in EBC. Separation prior to mass spectrometry was achieved using a C18 column with methanol and formic acid as the mobile phase, and characteristic precursor to product ion transitions of m/z 268 to 136 (for adenosine), m/z 348 to 136 (for AMP), and m/z 61 to 44 (for urea) were monitored for quantification. To correct for matrix effects, isotopically labeled adenosine, AMP, and urea were used as internal standards. Using these methods, we detected urea and the adenyl purines adenosine and AMP in EBC from seven subjects with cystic fibrosis (CF) and seven healthy controls and found that the AMP/urea ratio was elevated in the CF samples. These results demonstrate that mass spectrometry can be used successfully in EBC analysis to simultaneously detect a biomarker for airway inflammation and control for variable dilution. Copyright © 2008 John Wiley & Sons, Ltd.
A genetic screen for Saccharomyces cerevisiae mutants affecting proteasome function, using a ubiquitin‐independent substrate
Authors: Hoyt Martin A. , McDonough Stephen , Pimpl Stephan A. , Scheel Hartmut , Hofmann Kay , Coffino Philip
Published: February 2008

The great majority of proteasome substrates are marked for degradation by the attachment of polyubiquitin chains. Ornithine decarboxylase is degraded by the proteasome in the absence of this modification. We previously showed that this mechanism of degradation was conserved in eukaryotic cells. Here we use a reporter destabilized by mouse ornithine decarboxylase to screen non‐essential Saccharomyces cerevisiae deletion mutants. We identified novel mutants that affect both ubiquitin‐dependent and ‐independent proteasome degradation pathways. YLR021W (IRC25/POC3) and YPL144W (POC4) encode interacting proteins that function in proteasome assembly, with putative homologues widespread among eukaryotes. Several additional mutants suffered from defects in proteasome‐mediated proteolysis. These included mutants in the urmylation pathway of protein modification (but not the Urm1 modifier itself) and the Reg1 regulatory subunit of protein phosphatase 1. Finally, we noted increased rates of ornithine decarboxylase turnover in an rpn10Δ mutant in which the degradation of certain ubiquitinated substrates is impaired. Together, these results highlight the utility of a ubiquitin‐independent degron in uncovering novel factors affecting general and substrate‐specific proteasome function. Copyright © 2008 John Wiley & Sons, Ltd.
Vortex instability of mixed convection boundary layer flow adjacent to a non‐isothermal inclined surface in a porous medium with variable permeability
Authors: Elaiw A.M.
Published: February 2008

A linear stability theory is used to analyze the vortex instability of mixed convection boundary layer flow over an inclined heated surface in a porous medium with variable permeability. The variation of permeability in the vicinity of the solid boundary is approximated by an exponential function. The variation rate itself depends slowly on the streamwise coordinate, such as to allow the problem to possess a set of solutions, invariant under a group of transformations. The surface temperature is assumed to vary as a power function of the distance from the origin. In the main flow analysis, both the streamwise and normal component of the buoyancy force are retained in the momentum equations. The present formulation permits the angles of inclination ranging from 0 to close to 90 degrees from the horizontal. Local Nusselt number is presented for the uniform permeability (UP) and variable permeability (VP) cases. The critical Peclet numbers and the associated wave numbers are obtained for both the UP and VP cases. It is found that the VP effect tends to increase the heat transfer rate and destabilize the flow to the vortex mode of disturbance.
Effects of material inhomogeneity on the dynamic behavior of cracked piezoelectric solids: a BIEM approach
Authors: Rangelov T. , Dineva P. , Gross D.
Published: February 2008

Treated is an arbitrarily shaped anti‐plane shear crack in a finite inhomogeneous piezoelectric domain under time‐harmonic loading. Within a unified scheme different types of inhomogeneity are considered for which the material parameters may vary in two directions. The problem is solved by using a numerically efficient non‐hypersingular traction based boundary equation method (BIEM). The fundamental solutions for the different inhomogeneity types are derived in closed form. This is done by an appropriate functional transformation of the displacement vector in order to obtain a wave equation with constant coefficients and subsequently by application of the Radon transform. Numerical results for the stress intensity factors (SIF) are discussed for several examples. They show the effect of the material inhomogeneity and the efficiency of the method.
Can landscape properties predict occurrence of grey‐sided voles?
Authors: Christensen Pernilla , Ecke Frauke , Sandström Per , Nilsson Mats , Hörnfeldt Birger
Published: February 2008

There has been a long‐term decline in spring and fall numbers ofClethrionomys rufocanusin boreal Sweden in 1971–2005. Previous studies on permanent sampling plots in the centre of 2.5 × 2.5 km landscapes suggested that habitat fragmentation (sensu destruction) could have contributed to the decline. Therefore, we tested these findings in a field study and compared trapping results on the central sampling plots of landscapes with a low degree of fragmentation (LDF) and of “hot spot” type with trapping results in managed forest landscapes with a high degree of fragmentation (HDF). We predicted thatC. rufocanuswould be more common on the LDF plots. We used our permanent plots supplemented with a new sample of plots, mainly of the rare LDF type, inside or just outside the long‐term study area. Very few voles were trapped on both plot types, and no difference was found. However, a subsequent pilot study with trapping in a national park with large areas of pristine, unfragmented forest yielded more voles than in the managed, more fragmented, areas. Consequently, the initial field study data and some other recent data were also re‐analysed from a “local patch quality” perspective. This alternative approach revealed the positive importance of large focal patches of forest >60 years old and their content of old‐growth (pine) forest (>100 years). Interestingly, at the landscape level, the frequency distribution of patches of forest >60 years old, old‐growth (>100 years), and especially of old‐growth pine forest (>100 years), relative to the properties of plots withC. rufocanus, suggested that there are few forest patches left that are suitable forC. rufocanus. Our current results suggest that habitat fragmentation cannot be excluded as a contributing cause to the long‐term decline ofC. rufocanusin boreal Sweden.
Psychological Factors Associated with Emotional Responses to Receiving Genetic Risk Information
Authors: Bennett Paul , Wilkinson Clare , Turner Jim , Brain Kate , Edwards Rhiannon Tudor , Griffith Gethin , France Barbara , Gray Jonathon
Published: February 2008

This study identified levels of distress, and predictors of levels of distress, in women undergoing assessment for genetic risk of breast/ovarian cancer based on their family history. It comprised a cohort study following 154 women who completed questionnaires at entry into a cancer genetic assessment programme and following risk provision. Independent significant associates of anxiety following risk provision were age, neuroticism, feeling hopeless about developing cancer, a perceived lack of control over developing cancer, lack of a social confidant, and a coping response involving acceptance/resignation. Depression was associated with age, neuroticism, feeling hopeless about developing cancer, lack of social confidant, and a coping response involving acceptance/resignation. To avoid high levels of psychological morbidity in future cohorts undergoing cancer genetic risk assessment, information should be given that emphasises that some degree of control over health outcomes through behaviour change or increased surveillance is possible.
Aggregated seed dispersal by wreathed hornbills at a roost site in a moist evergreen forest of Thailand
Authors: Kitamura Shumpei , Yumoto Takakazu , Noma Naohiko , Chuailua Phitaya , Maruhashi Tamaki , Wohandee Prawat , Poonswad Pilai
Published: February 2008

Hornbills (Bucerotidae) are widely regarded as important seed dispersers in tropical forests in Africa and Asia. We investigated how the roosting behavior of wreathed hornbills (Aceros undulatus) influences seed deposition and seedling survival at a roost site in a moist evergreen forest of Khao Yai National Park, Thailand. Fallen fruits and seeds were collected in traps that were placed around a roosting site for 14 months, and seedlings were monitored in adjacent quadrats for 3 years. Seedfall and seedlings of species represented in the hornbill diet occurred at significantly higher densities in the traps and quadrats located beneath the crown of the roosting tree than in those located beyond the crown. With the exception of Cinnamomum subavenium, the seeds and seedlings of most diet species rarely survived beyond the first year. The quality of hornbill dispersal to this roosting site may be poor due to the highly concentrated seedfall, which results in high seed and seedling mortality. However, the number of seeds deposited by each hornbill each day at roosting sites is relatively low. Wreathed hornbills are primarily scatter dispersers during the day and probably serve as agents of seed dispersal in the moist evergreen forest of Khao Yai.
Prognostic value and diagnostic potential of cardiopulmonary exercise testing in patients with chronic heart failure
Authors: Ingle Lee
Published: February 2008

Cardiopulmonary exercise testing (CPET) is a well established technique for stratifying cardiovascular risk in patients with chronic heart failure (CHF). Important prognostic variables include a reduced peak oxygen uptake which has a central use in cardiac transplant selection, and the abnormal relation between minute ventilation (VE) and carbon dioxide production (VCO2), often referred to as the elevated VE/VCO2 slope. We will discuss the pathophysiology of these abnormal responses to exercise in CHF, and how these are interpreted during CPET. The potential of CPET for diagnosing circulatory, respiratory, metabolic, musculoskeletal or mixed limitations is an emerging field of research. We will speculate on how CHF manifests during CPET, and clarify the pathophysiological basis of these exercise responses. To improve our understanding of the diagnostic value of CPET, further investigation is required by clinicians to develop reference ranges for CHF patients from a co‐ordinated multicentre approach. The use of CPET technology is becoming increasingly prevalent in cardiology services, and it is likely that, in the future, CPET will take a more prominent role in guiding patient management provision.
Angiotensin II and III suppress food intake via angiotensin AT2 receptor and prostaglandin EP4 receptor in mice
Authors: Ohinata Kousaku , Fujiwara Yoko , Fukumoto Shingo , Iwai Masaru , Horiuchi Masatsugu , Yoshikawa Masaaki
Published: February 2008

Intracerebroventricularly administered angiotensin (Ang) II and III dose‐dependently suppressed food intake in mice and their anorexigenic activities were inhibited by AT2 receptor‐selective antagonist. Ang II did not suppress food intake in AT2 receptor‐knockout mice, while it did significantly in wild‐type and AT1 receptor‐knockout mice. The suppression of food intake in AT1 receptor‐knockout mice was smaller than that in wild‐type. The anorexigenic activities of Ang II and III were also blocked by a selective antagonist for prostaglandin EP4 receptor. Taken together, centrally administered Ang II and III may decrease food intake through AT2 receptor with partial involvement of AT1 receptor, followed by EP4 receptor activation, which is a novel pathway regulating food intake.
Introduction: Acquisition of food-related behaviours in children: critical windows for later health. An international pre-FENS congress symposium, Paris July 9th, 2007
Authors: Bellisle France
Published: February 2008

The children of Europe, like those of most other parts of the world, are experiencing rapid changes in their lifestyle conditions. Numerous varieties of palatable foods are now available at all times in all places, or nearly so.
Cognitive schemas: how can we use them to improve children's acceptance of diverse and unfamiliar foods?
Authors: Pliner Patricia
Published: February 2008

Foods represent important stimuli for humans, especially for human children. After weaning, it is important that children quickly acquire knowledge about their food environment to avoid ingesting potentially dangerous substances. This paper discusses this process and its implications in terms of schemas. The effects of providing positive taste information to novel foods and of adding familiar flavors to novel foods are interpreted by means of the schema construct. A means of changing schemas through exposure to schema-inconsistent information is presented and evidence for its efficacy is described. Finally, the effect of early variety on subsequent willingness to eat unfamiliar foods is described and once again interpreted by means of the schema construct.
Genetic and environmental determinants of children's food preferences
Authors: Wardle Jane , Cooke Lucy
Published: February 2008

Omnivores have the advantage of a variety of food options but face a challenge in identifying foods that are safe to eat. Not surprisingly, therefore, children show a relative aversion to new foods (neophobia) and a relative preference for familiar, bland, sweet foods. While this may in the past have promoted survival, in the modern food environment it could have an adverse effect on dietary quality. This review examines the evidence for genetic and environmental factors underlying individual differences in children's food preferences and neophobia. Twin studies indicate that neophobia is a strongly heritable characteristic, while specific food preferences show some genetic influence and are also influenced by the family environment. The advantage of the malleability of human food preferences is that dislike of a food can be reduced or even reversed by a combination of modelling and taste exposure. The need for effective guidance for parents who may be seeking to improve the range or nutritional value of foods accepted by their children is highlighted.
Child nutrition and growth: butterfly effects?
Authors: Bellisle France
Published: February 2008

The international symposium organised by the Danone Institute as a pre-congress satellite of the European Nutrition Societies Congress, in Paris, in July 2007, brought together experts of child nutrition and behaviour. These experts coming from several countries of Europe and North America shared their views on the impact of numerous factors affecting child eating and health in present-day developed societies. Topics included nutritional influences during foetal life, early life development of food likes and dislikes, neophobia, ability for energy regulation, impact of media and advertisement, etc. Most contributions addressed the obesity epidemics and the problems associated with body weight control. Other aspects of child health were also considered, for example the nutritional challenge of adequately feeding children with type 1 diabetes. The nine speakers were asked to underline practical strategies to improve nutrition in early life, so as to maximise health, growth and quality of life in today's environment. The present paper is a summary of the ideas expressed by the experts, highlighting agreements, convergences, and occasional disagreements between expert opinions.
DSM-IV pathological gambling in the National Comorbidity Survey Replication
Authors: Kessler R. C. , Hwang I. , LaBrie R. , Petukhova M. , Sampson N. A. , Winters K. C. , Shaffer H. J.
Published: February 2008

Background

Little is known about the prevalence or correlates of DSM-IV pathological gambling (PG).

Method

Data from the US National Comorbidity Survey Replication (NCS-R), a nationally representative US household survey, were used to assess lifetime gambling symptoms and PG along with other DSM-IV disorders. Age of onset (AOO) of each lifetime disorder was assessed retrospectively. AOO reports were used to study associations between temporally primary disorders and the subsequent risk of secondary disorders.

Results

Most respondents (78.4%) reported lifetime gambling. Lifetime problem gambling (at least one Criterion A symptom of PG) (2.3%) and PG (0.6%) were much less common. PG was significantly associated with being young, male, and Non-Hispanic Black. People with PG reported first gambling significantly earlier than non-problem gamblers (mean age 16.7 v. 23.9 years, z=12.7, p<0.001), with gambling problems typically beginning during the mid-20s and persisting for an average of 9.4 years. During this time the largest annual gambling losses averaged US$4800. Onset and persistence of PG were predicted by a variety of prior DSM-IV anxiety, mood, impulse-control and substance use disorders. PG also predicted the subsequent onset of generalized anxiety disorder, post-traumatic stress disorder (PTSD) and substance dependence. Although none of the NCS-R respondents with PG ever received treatment for gambling problems, 49.0% were treated at some time for other mental disorders.

Conclusions

DSM-IV PG is a comparatively rare, seriously impairing, and undertreated disorder whose symptoms typically start during early adulthood and is frequently secondary to other mental or substance disorders that are associated with both PG onset and persistence.
Variable export fluxes and efficiencies for calcite, opal, and organic carbon in the Atlantic Ocean: A ballast effect in action?
Authors: Thomalla Sandy J. , Poulton Alex J. , Sanders Richard , Turnewitsch Robert , Holligan Patrick M. , Lucas Mike I.
Published: February 2008

Latitudinal variability in export fluxes and efficiencies (ThE) of calcite, opal, and particulate organic carbon (POC) were examined during a basin‐scale Atlantic Ocean cruise. A clear relationship between integrated euphotic zone POC and calcite export combined with similarities in average ThE for calcite (0.26), opal (0.31), and POC (0.29) implies a potential association between biomineral and POC export. However, such similarity conceals substantial uncorrelated variability when ThE values are compared on regional scales, with ThE of POC often being much higher than that of calcite or opal. High‐euphotic zone ThE for POC (0.3–0.4) relative to that found in deep sea sediment traps (<0.05) suggests that considerable remineralization occurs below the euphotic zone. We suggest (1) that regional variability in the mechanisms by which biominerals and POC become associated are more important in determining the efficient export of organic carbon than that of ballast materials; and (2) that, because of the preferential remineralization of POC relative to calcite/opal dissolution during subeuphotic processes, the potential for effective ballasting increases with depth in the water column.
Sulfate‐methane transition as a proxy for average methane hydrate saturation in marine sediments
Authors: Bhatnagar Gaurav , Chapman Walter G. , Dickens Gerald R. , Dugan Brandon , Hirasaki George J.
Published: February 2008

We develop a relationship between the sulfate‐methane transition (SMT) and average gas hydrate saturation (AGHS) for systems dominated by methane migration from deeper sources. The relationship is explained by a one‐dimensional numerical model that simulates gas hydrate accumulation in marine sediments. Higher methane fluxes result in shallow SMT depths and high AGHS, while lower methane fluxes result in deep SMTs and low AGHS. We also generalize the variation between AGHS and scaled SMT depth, a procedure that aids prediction of AGHS at different sites from observations of the SMT, such as along Cascadia Margin.
Climatology of mesopause region temperature, zonal wind, and meridional wind over Fort Collins, Colorado (41°N, 105°W), and comparison with model simulations
Authors: Yuan Tao , She Chiao‐Yao , Krueger David A. , Sassi Fabrizio , Garcia Rolando , Roble Raymond G. , Liu Han‐Li , Schmidt Hauke
Published: February 2008

Between May 2002 and April 2006, many continuous observations of mesopause region temperature and horizontal wind, each lasting longer than 24 h (termed full‐diurnal‐cycle observations), were completed at the Colorado State University Na Lidar Facility in Fort Collins, Colorado (41°N, 105°W). The combined data set consists of 120 full‐diurnal‐cycle observations binned on a monthly basis, with a minimum of 7 cycles in April and a maximum of 18 cycles in August. Each monthly data set was analyzed to deduce mean values and tidal period perturbations. After removal of tidal signals, monthly mean values are used for the study of seasonal variations in mesopause region temperature, zonal and meridional winds. The results are in qualitative agreement with our current understanding of mean temperature and wind structures in the midlatitude mesopause region with an observed summer mesopause of 167 K at 84 km, summer peak eastward zonal wind of 48 m/s at 94 km, winter zonal wind reversal at ∼95 km, and peak summer (pole) to winter (pole) meridional flow of 17 m/s at 86 km. The observed mean state in temperature, zonal and meridional winds are compared with the predictions of three current general circulation models, i.e., the Whole Atmosphere Community Climate Model version 3 (WACCM3) with two different simulations of gravity wavefields, the Hamburg Model of the Neutral and Ionized Atmosphere (HAMMONIA), and the 2003 simulation of the Thermosphere‐Ionosphere‐Mesosphere‐Electrodynamics General Circulation Model (TIME‐GCM). While general agreement is found between observation and model predictions, there exist discrepancies between model prediction and observation, as well as among predictions from different models. Specifically, the predicted summer mesopause altitude is lower by 3 km, 8 km, 3 km, and 1 km for WACCM3 the two WACCM runs, HAMMONIA, and TIME‐GCM, respectively, and the corresponding temperatures are 169 K, 170 K, 158 K, and 161 K. The model predicted summer eastward zonal wind peaks to 71 m/s at 102 km, to 48 m/s at 84 km, to 75 m/s at 93 km, and to 29 m/s at 94 km, in the same order. The altitude of the winter zonal wind reversal and seasonal asymmetry of the pole‐to‐pole meridional flow are also compared, and the importance of full‐diurnal‐cycle observations for the determination of mean states is discussed.
Identification of the bacterial symbiont Entotheonella sp. in the mesohyl of the marine sponge Discodermia sp.
Authors: Brück Wolfram M , Sennett Susan H , Pomponi Shirley A , Willenz Philippe , McCarthy Peter J
Published: February 2008

The lithistid sponge Discodermia dissoluta (family Theonellidae), is found in deep-waters throughout the Caribbean sea and is the source of discodermolide, a natural product with potential anticancer properties, and other secondary metabolites. As with other sponges, large numbers of microbes are harbored in the sponge mesohyl. The microbial population of the sponge mesohyl shows an abundance of large filamentous microbes. Fractionation of the dissociated sponge allowed enrichment of this microbe, which was then identified by analysis of the 16S rRNA genes. Its identity was confirmed through the use of fluorescent in situ hybridization. These studies have allowed the identification of this eubacterial microbe as belonging to the genus Entotheonella.
Protein kinase and protein phosphatase expression in amyotrophic lateral sclerosis spinal cord
Authors: Hu J.‐H. , Zhang H. , Wagey R. , Krieger C. , Pelech S. L.
Published: February 2008

The Kinetworks™ multi‐immunoblotting technique was used to evaluate the expressions of 78 protein kinases, 24 protein phosphatases and phosphorylation states of 31 phosphoproteins in thoracic spinal cord tissue from control subjects and patients having the sporadic form of amyotrophic lateral sclerosis (ALS). In both the cytosolic (C) and particulate (P) fractions of spinal cord from ALS patients as compared with controls, there were increased levels of calcium/calmodulin‐dependent protein kinase kinase (CaMKK; C = 120% increase/P = 580% increase;% change, compared with control), extracellular regulated kinase 2 (ERK2; C = 120% increase/P = 170% increase), G protein‐coupled receptor kinase 2 (GRK2; C = 140% increase/P = 140% increase), phospho‐Y279/216 glycogen synthase kinase 3 α/β (GSK3α/β; C = 90% increase/P = 220% increase), protein kinase B α (PKBα; C = 360% increase/P = 200% increase), phospho‐T638 PKCα/β (C = 630% increase/P = 170% increase), cGMP‐dependent protein kinase (PKG; C = 100% increase/P = 75% increase), phospho‐T451 dsRNA‐dependent protein kinase (PKR; C = 2600% increase/P = 3330% increase), ribosomal S6 kinase 1 (RSK1; C = 750% increase/P = 630% increase), phospho‐T389 p70 S6 kinase (S6K; C = 1000% increase/P = 460% increase), and protein‐tyrosine phosphatase 1 δ (PTP1δ; C = 43% increase/P = 70% increase). Cytosolic increases in phospho‐α‐S724/γ‐S662 adducin (C = 15650% increase), PKCα (C = 100% increase) and PKCζ (C = 190% increase) were found in ALS patients as compared with controls, while particulate increases in cAMP‐dependent protein kinase (PKA; 43% increase), protein kinase C β (PKCβ; 330% increase), and stress‐activated protein kinase β (SAPKβ; 34% increase) were also observed. Cyclin‐dependent kinase‐associated phosphatase (KAP) was apparently translocated, as it was reduced (31% decrease) in cytosolic fractions but elevated (100% increase) in particulate fractions of ALS spinal cord tissue. Our observations indicate that ALS is associated with the elevated expression and/or activation of many protein kinases, including PKCα, PKCβ, PKCζ and GSK3α/β, which may augment neural death in ALS, and CaMKK, PKBα, Rsk1, S6K, and SAPK, which may be a response to neuronal injury that potentially can mitigate cell death.
Poly(ADP‐ribose) polymerase‐1 activity promotes NF‐κB‐driven transcription and microglial activation: implication for neurodegenerative disorders
Authors: Chiarugi Alberto , Moskowitz Michael A.
Published: February 2008

Excessive release of proinflammatory products by activated glia causes neurotoxicity and participates in the pathogenesis of neurodegenerative disorders. Recently, poly(ADP‐ribose) polymerase‐1 (PARP‐1) has been shown to play a key role in nuclear factor kappa B (NF‐κB)‐driven expression of inflammatory mediators by glia during the neuroimmune response. Here we report the novel finding that the enzymatic activity of PARP‐1 promotes, in an β‐nicotinamide adenine dinucleotide‐dependent fashion, the DNA binding of NF‐κB in microglia exposed to lipopolysaccharides, interferon‐γ or β‐amyloid 1–40. Consistently, we found that targeting NF‐κB‐dependent glial activation with pharmacological inhibitors of PARP‐1 enzymatic activity reduces expression of inflammatory mediators such as inducible nitric oxide synthase, interleukin 1β, tumor necrosis factor α and amyloid precursor protein, and reduces the neurotoxic potential of activated glia in vitro. Importantly, pharmacological inhibition of lipopolysaccharide‐induced poly(ADP‐ribose) formation in vivo suppresses neuroinflammation and related neural cell death. Our findings build on prior published reports in PARP‐1 null mice and highlight the importance of PARP‐1 enzymatic activity in transcriptional control during glial activation, identifying PARP‐1 activity‐dependent regulation of NF‐κB as a novel pharmacological target for therapeutic intervention in the treatment of acute and chronic neurodegenerative disorders.
Regional brain serotonin synthesis is increased in the olfactory bulbectomy rat model of depression: an autoradiographic study
Authors: Watanabe Arata , Tohyama Yoshihiro , Nguyen Khanh Q. , Hasegawa Shu , Debonnel Guy , Diksic Mirko
Published: February 2008

Serotonin synthesis rates were evaluated using α‐[14C]methyl‐l‐tryptophan (α‐MTrp) autoradiographic methods in olfactory bulbectomized (OBX) rats. They were significantly (p < 0.05) increased in the frontal (50%) and parietal (40%) cortices, superior olive (over 30%), and the substantia nigra (30%) in the OBX rats as compared to the sham operated animals. There were also increases in 5‐hydroxytryptamine (5‐HT) synthesis in some limbic areas: the cingulate (32%), the medial forebrain bundle (58%), the hippocampus (13–25%) and the thalamus (22–40%). The largest increase in 5‐HT synthesis after OBX was observed in the sensory‐motor cortex (67%). 5‐HT synthesis rates were significantly decreased in the dorsal and medial raphe nuclei, but there was no significant change the ventral tegmental area and the locus coeruleus following OBX. These results indicate that olfactory bulbectomy causes an imbalance in 5‐HT synthesis in some projection areas by disproportionally increasing 5‐HT synthesis rates in specific brain regions and making more 5‐HT available for neurotransmission. This imbalance in 5‐HT synthesis and the subsequent elevation of tissue 5‐HT may be responsible for the creation of non‐physiological circuitry which may, in part, be reflected in the symptoms resembling human depression.
Iron toxicity in organotypic cultures of hippocampal slices: role of reactive oxygen species
Authors: Liu Ruolan , Liu Wei , Doctrow Susan R. , Baudry Michel
Published: February 2008

Free iron has been assumed to potentiate oxygen toxicity by generating reactive oxygen species (ROS) via the iron‐catalyzed Haber‐Weiss reaction, leading to oxidative stress. ROS‐mediated iron cytotoxicity may trigger apoptotic cell death. In the present study, we used iron treatment of organotypic cultures of hippocampal slices to study potential mechanisms involved in iron‐induced neuronal damage. Exposure of mature hippocampal slices to ferrous sulfate resulted in concentration‐ and time‐dependent cell death. After iron treatment, markers of ROS formation and lipid peroxidation, i.e. intensity of dichlorofluorescein (DCF) fluorescence and levels of thiobarbiturate reactive substances (TBARS), were significantly increased. Levels of cytochromecwere increased while levels of pro‐caspase‐9 and pro‐caspase‐3 were decreased in cytosolic fractions of iron‐treated hippocampal slice cultures. Treatment of cultured slices with a synthetic catalytic ROS scavenger, EUK‐134, provided between 50 and 70% protection against various parameters of cell damage and markers of oxidative stress. In addition, inhibition of caspase‐3 activity by Ac‐DEVDcho partially protected cells from iron toxicity. The combination of EUK‐134 and Ac‐DEVDcho resulted in an almost complete blockade of iron‐induced damage. These results indicate that iron elicits cellular damage predominantly by oxidative stress, and that ROS‐mediated iron toxicity may involve cytochrome c‐ and caspase‐3‐dependent apoptotic pathways.