bluuebunny/crossref_metadata_2025 huggingface dataset:
Innervation of orexin/hypocretin neurons by GABAergic, glutamatergic or cholinergic basal forebrain terminals evidenced by immunostaining for presynaptic vesicular transporter and postsynaptic scaffolding proteins
Authors: Henny Pablo , Jones Barbara E.
Published: October 2006

Orexin/hypocretin (Orx) neurons are critical for the maintenance of waking in association with behavioral arousal and postural muscle tone, since with their loss narcolepsy with cataplexy occurs. Given that basal forebrain (BF) neurons project to the hypothalamus and play important diverse roles in sleep/wake states, we sought to determine whether acetylcholine (ACh), glutamate (Glu), and/or GABA‐releasing BF neurons innervate and could thereby differentially regulate the Orx neurons. From discrete injections of biotinylated dextran amine (BDA, 10,000 MW) into the magnocellular preoptic nucleus (MCPO) and substantia innominata (SI) in the rat, BDA‐labeled fibers projected to the lateral hypothalamus (LH), perifornical area (PF), and dorsomedial hypothalamus (DMH), where ∼41%, ∼11%, and 9% of Orx‐positive (+) neurons were respectively contacted in each region. Employing triple fluorescent staining for Orx, BDA, and presynaptic vesicular (V) transporters (T), we found that only 4% of the innervated Orx+ neurons in the LH were contacted by BDA+[VAChT+] terminals, whereas ∼31% and ∼67% were respectively contacted by BDA+[VGluT2+] and BDA+[VGAT+] terminals. In 3D‐rendered and rotated confocal images, we confirmed the latter contacts and examined staining for postsynaptic proteins PSD‐95, a marker for glutamatergic synapses, and gephyrin, a marker for GABAergic synapses, that were located on Orx+ neurons facing BDA‐labeled terminals in ∼20% and ∼50% of contacts, respectively. With such synaptic input, BF glutamatergic neurons can excite Orx neurons and thus act to maintain behavioral arousal with muscle tone, whereas GABAergic neurons can inhibit Orx neurons and thus promote behavioral quiescence and sleep along with muscle atonia. J. Comp. Neurol. 499:645–661, 2006. © 2006 Wiley‐Liss, Inc.
Modular neuropile organization in the Drosophila larval brain facilitates identification and mapping of central neurons
Authors: Iyengar Balaji G. , Chou C. Jennifer , Sharma Abhinav , Atwood Harold L.
Published: October 2006

Elucidating how neuronal networks process information requires identification of critical individual neurons and their connectivity patterns. For this purpose, we used the third‐instar Drosophila larval brain and applied reverse‐genetic tools, immunolabeling procedures, and 3D digital reconstruction software. Consistent topological definition of neuropile compartments in the larval brain can be obtained through simple fluorescence‐immunolabeling methods. The modular neuropiles can be used as a fiducial framework for mapping the projection patterns of individual neurons labeled with green fluorescent protein (GFP). GFP‐labeled neurons often exhibit dendrite‐like arbors as well as clustered varicose terminals on neurite branches that innervate identifiable neuropile compartments. We identified candidate cholinergic interneurons in genetic mosaic brains that overlap with the larval optic nerve terminus. By using the neuropile framework, we demonstrate that the candidate visual interneurons are not a subset of the previously identified circadian pacemaker neurons that also contact the larval optic nerve terminus; they may represent parallel pathways in the processing of visual inputs. Thus, in the Drosophila larval brain, modular neuropiles can be used as a framework for systematically identifying, mapping, and classifying interneurons; understanding their roles in behavior can then be pursued further. J. Comp. Neurol. 499:583–602, 2006. © 2006 Wiley‐Liss, Inc.
Perceived criticism, marital interaction and relapse in unipolar depression—findings from a Korean sample
Authors: Kwon Jung‐Hye , Lee Yuri , Lee Min‐Soo , Bifulco Antonia
Published: October 2006

Perceived criticism by partner (PC) has been demonstrated to be a powerful predictor of depressive relapse. The purpose of this prospective 11‐month study was to replicate this finding in an outpatient series of married women in Korea, but also to further explore the nature of PC in terms of qualities of the marital relationship and dysfunctional attitudes. The subjects consisted of 27 married female outpatients who had all been treated for major depression, but were in recovery at time of first contact or shortly after. All were interviewed at time 1 and then again after 11 months at time 2 to ascertain major depressive episode using the Korean version of SADS as well as completing the BDI. At first contact, questionnaire and interview assessments were used for marital quality and dysfunctional attitudes denoting dependency. There was a significant relationship between the single‐item PC and depressive relapse at follow‐up as predicted. This relationship was not enhanced by using the expanded item scale. PC and/or PC‐E were significantly correlated with marital quality variables, specifically lack of emotional support from partner, negative interaction and dependence on partner. The study shows that perceived criticism by spouse is a predictor of depressive relapse in Korean outpatients and that this appears to reflect actual negative characteristics of the marital relationship as well as the depressed person's high dependence on the relationship. These results support the importance of improving marital interactions in preventing relapse in depression. Copyright © 2006 John Wiley & Sons, Ltd.
Factors influencing levels of research activity in clinical psychologists: a new model
Authors: Holttum Sue , Goble Laura
Published: October 2006

There are concerns in the USA and UK about low levels of research activity amongst clinical psychologists emerging from doctoral level training. The authors explore existing evidence and theory pertaining to this phenomenon. Three relevant theoretical strands are identified, along with related empirical studies and commentaries in practitioner journals. These different sources are integrated to suggest a more complete model of factors influencing clinical psychologists' research intentions, and in turn research activity itself: vocational preferences, research training experienced during qualifying training, practice context, value placed on expected outcomes of doing research, perceived norms for clinical psychologists in relation to doing research, research self‐efficacy, professional identity and, most tentatively, sex role identity. Our new model points to training interventions, either pre‐ or post‐qualification, that may increase the likelihood of clinical psychologists carrying out clinical research that will contribute to their profession's knowledge base, beyond their time in qualifying training. Copyright © 2006 John Wiley & Sons, Ltd.
Therapy with the hsp60 peptide DiaPep277™ in C‐peptide positive type 1 diabetes patients
Authors: Huurman Volkert A. L. , Decochez Katelijn , Mathieu Chantal , Cohen Irun R. , Roep Bart O.
Published: October 2006

Background

Type 1 diabetes results from a T‐cell mediated autoimmune destruction of insulin‐producing pancreatic beta‐cells. The 60‐kDa heat‐shock protein (hsp60) is one of the known target self‐antigens. An immunogenic peptide from hsp60, p277, arrested beta‐cell destruction and maintained insulin production in newly diabetic non‐obese diabetic (NOD) mice. A randomized, double‐blind, phase Ib/II study of peptide treatment was undertaken in recent onset type 1 diabetes patients with remaining insulin production.

Methods

Forty‐eight recent onset type 1 diabetes patients were assigned subcutaneous injections of 0.2, 1.0 or 2.5 mg peptide DiaPep277 (n = 12 per dosage) at entry, and 1, 6 and 12 months, or four placebo injections (n = 12). The primary clinical endpoints were safety and efficacy (glucagon‐stimulated C‐peptide production at 6 and 12 months); secondary endpoints were HbA1c levels and daily insulin dose adjusted for body weight at 2, 6, 12 and 18 months.

Results

C‐peptide levels decreased over time in all groups except the 2.5 mg‐treated. The decrease in C‐peptide production was less in treated patients versus placebo, mostly in the 2.5 mg group. HbA1c increased significantly in the 1.0 mg group and in the 2.5 mg group at 2 and 18 months, respectively. No differences were seen in daily insulin doses. One patient was withdrawn from the study possibly owing to a treatment‐related adverse event.

Conclusions

Multiple DiaPep277 peptide administration seems safe and may have a beneficial effect on C‐peptide levels over time, but this finding is not supported by lower HbA1c levels or daily insulin requirement. Further investigation on a larger scale is warranted. Copyright © 2006 John Wiley & Sons, Ltd.
Macrophages promote collagen fibrillogenesis around terminal end buds of the developing mammary gland
Authors: Ingman Wendy V. , Wyckoff Jeff , Gouon‐Evans Valerie , Condeelis John , Pollard Jeffrey W.
Published: October 2006

Development of the ductal network in the mammary gland is dependent in part on the presence of macrophages. Here we utilize multi‐photon microscopy and second harmonic generation to describe terminal end bud 3‐dimensional structure and the organization of the surrounding collagen matrix. We have applied this approach to analyze the effect of macrophage deficiency on terminal end bud structure and collagen organization, using mice homozygous for a null mutation in the colony stimulating factor‐1 gene (Csf1op/Csf1op). Primary terminal end buds have an oblong shape, with long collagen I fibers close to the neck of the terminal end bud and radiating upwards in the direction of growth. Around the terminal end buds, the amount of total collagen I detected by antibody staining was not affected by macrophage deficiency. However the amount of collagen I organized into long fibers, detected by second harmonic generation signal, was reduced in Csf1op/Csf1op mice. Macrophage deficiency also caused terminal end buds to be rounder and shorter. These studies reveal a role for macrophages in collagen fibrillogenesis and in organization of the structure of terminal end buds. Developmental Dynamics 235:3222–3229, 2006. © 2006 Wiley‐Liss, Inc.
Methyltestosterone efficiently induces male development in the self‐fertilizing hermaphrodite fish, Kryptolebias marmoratus
Authors: Kanamori Akira , Yamamura Aki , Koshiba Satoshi , Lee Jae‐Seong , Orlando Edward F. , Hori Hiroshi
Published: October 2006

A hermaphrodite fish, Kryptolebias marmoratus, is the only known vertebrate that reproduces by self‐fertilization. In nature, males have been rarely observed. Low‐temperature treatment during late embryonic stages is known to induce males but its efficacy is variable. Here we report that 17α‐methyltestosterone (MT) treatment of the embryos converted most of the fish to males. We examined a time course of this male induction with histological and marker gene expression analyses. Oogenesis started in the gonads of the control embryo at hatching; spermatogenesis did not start until two months after hatching. In the MT‐treated fish, oogenesis started initially as in the control but stopped completely within one month after hatching. Instead, spermatogonial proliferation started earlier than in the control fish and progressed to full spermatogenesis. Expression profiles of the sex‐specific marker genes corresponded well with histological observations. From one month after hatching, expression of an oocyte‐specific marker, figα, and a testicular somatic cell marker, dmrt1, started to increase in the control and in the MT‐treated fish, respectively. genesis 44:495–503, 2006. © 2006 Wiley‐Liss, Inc.
Potential of human serum albumin as chiral selector of basic drugs in affinity electrokinetic chromatography‐partial filling technique
Authors: Martínez‐Gómez Maria A. , Villanueva‐Camañas R. M. , Sagrado Salvador , Medina‐Hernández Maria J.
Published: October 2006

The enantiomeric resolution of compounds using HSA by means of affinity EKC (AEKC)‐partial filling technique is the result of a delicate balance between different experimental variables such as protein concentration, running pH (background electrophoretic buffer (BGE), protein, and compound solutions), and plug length. In this paper, the possibility of using HSA as chiral selector for enantioseparation of 28 basic drugs using this methodology is studied. The effect of the physicochemical parameters, the structural properties of compounds, and compound–HSA protein binding percentages over their chiral resolution with HSA is outlined. Based on the results obtained, a decision tree is proposed for the “a priori” prediction of the capability of HSA for enantioseparation of basic drugs in AEKC. The results obtained indicated that enantioresolution of basic compounds with HSA depends on the hydrophobicity, polarity, and molar volume of compounds.
Family income, parenting styles and child behavioural–emotional outcomes
Authors: Dooley Martin , Stewart Jennifer
Published: October 2006

A positive relationship between income and child outcomes has been observed in data from numerous countries. A key question concerns the extent to which this association represents a causal relationship as opposed to unobserved heterogeneity. We use data from the National Longitudinal Survey of Children and Youth to implement a series of empirical strategies for estimating the existence and size of the effect of income on behavioural–emotional outcomes. We also examine the role of parenting style. Our results indicate that there is little evidence of an effect of income on behavioural–emotional scores. The exclusion of parenting style from the models was found to not bias the estimated income effect, but parenting style was found to have a consistent impact on child outcomes. Copyright © 2006 John Wiley & Sons, Ltd.
Sectoral labour supply, choice restrictions and functional form
Authors: Dagsvik John K. , StrØm Steinar
Published: October 2006

In this paper we discuss a general framework for analysing labour supply behaviour in the presence of complicated budget and quantity constraints, of which some are unobserved. The individual's labour supply decision is viewed as a choice from a set of discrete alternatives (jobs). These jobs are characterized by attributes such as hours of work, sector‐specific wages and other sector‐specific aspects of the jobs.

The labour supply model for married women is estimated on Norwegian data. Wage elasticities and the outcome of a tax reform experiment show that overall labour supply is moderately elastic, but these modest overall responses shadow for much stronger inter‐sectoral changes. Our model is compared with a discrete choice model in which the utility is assumed to be a polynomial. We show that our estimated model has a more economically sensible interpretation and fits the data as well as the alternative approach. Copyright © 2006 John Wiley & Sons, Ltd.
Semi‐parametric estimation of consumption‐based equivalence scales: the case of Germany
Authors: Wilke Ralf A.
Published: October 2006

Consumption‐based equivalence scales are estimated by applying the extended partially linear model (EPLM) to the 1998 German Income and Consumption Survey (EVS). In this model the equivalence scales are identified from nonlinearities in household demand. The econometric framework should not therefore impose strong restrictions on the functional forms of household expenditure shares. The chosen semi‐parametric specification meets this requirement. It is flexible, it yields$\sqrt{N}$‐consistent parameter estimates and it is consistent with consumer theory. Estimated equivalence scales are below or in the range of the expert equivalence scales of the German social benefits system. Copyright © 2006 John Wiley & Sons, Ltd.
Gender, ethnicity, development, and risk: Mentoring and the consideration of individual differences
Authors: Darling Nancy , Bogat G. Anne , Cavell Timothy A. , Murphy Susan Elaine , Sánchez Bernadette
Published: October 2006

Individual differences shape the needs and characteristics of protégés, the processes through which mentoring may influence protégés' developmental trajectories, and the social networks into which the mentors enter. The literature on the influences of gender, ethnicity, and age on mentoring is reviewed and discussed as examples of how mentoring programs may have different influences on, and outcomes for, specific groups of youth. A focus on individual differences will help facilitate the development of mentoring programs that create a close fit between the needs of protégés and the services offered by the programs, as well as greater insight into what are the key elements of program effectiveness. © 2006 Wiley Periodicals, Inc.
Analysis of changes in optical fibers during arc‐fusion splicing by use of quantitative phase imaging
Authors: Dragomir N.M. , Ampen‐Lassen E. , Baxter G.W. , Pace P. , Huntington S.T. , Farrell P.M. , Stevenson A.J. , Roberts A.
Published: October 2006

A non‐interferometric imaging technique in conjunction with Abel inversion is used to directly and quantitatively examine the changes in optical fibers due to the heating produced during arc‐fusion splicing as a function of fusion arc parameters. Phase images in the vicinity of a fusion splice are obtained using Quantitative Phase Microscopy, allowing the refractive‐index change to be reconstructed with high spatial resolution. This simple, nondestructive method confirms that, for a fixed arc current, while the fusion time increases, the refractive‐index of both fiber cores within the fusion region decreases in magnitude, the core region broadens, and the axial gradient decreases. Microsc. Res. Tech., 2006. © 2006 Wiley‐Liss, Inc.
Phototoxicity and fluorotoxicity combine to alter the behavior of neutrophils in fluorescence microscopy based flow adhesion assays
Authors: Smith Emily , Lally Frank , Stone Michael A. , Shaw John S. , Nash Gerard B. , Buckley Christopher D. , Ed Rainger G.
Published: October 2006

The use of fluorescent probes that allow visualization of leukocyte‐endothelial cell (EC) interactions has greatly informed our understanding of leukocyte recruitment. However, effects of these agents on the biological functions of leukocytes are poorly described, leading to concerns about the interpretation of such data. Here we used two flow‐based neutrophil adhesion assays to compare the effects of phase contrast illumination (PCI) with high intensity illumination (HII) used for fluorescent microscopy, in the presence or absence of five commonly used fluorochromes. Isolated neutrophils were either (1) perfused across P‐selectin to establish a population of rolling cells, which were subsequently activated with fMLP; or (2) perfused across EC activated with TNF‐α. In the absence of fluorescent dyes, HII did not affect levels of leukocyte adhesion; however, subsequent neutrophil behavior was dramatically altered when compared with cells under PCI, for example, dramatically reducing their migration velocities. In the presence of fluorescent dyes, the effects of HII were exacerbated, although the precise nature of the biological effects of these probes was agent specific. Thus, for the first time, our experiments describe the effects of fluorescent microscopy on the separate stages of the neutrophil recruitment process and reveal a previously unsuspected effect of HII on neutrophil migration. Microsc. Res. Tech., 2006. © 2006 Wiley‐Liss, Inc.
What are the relations between mechanics, gait parameters, and energetics in terrestrial locomotion?
Authors: Hoyt Donald F. , Wickler Steven J. , Dutto Darren J. , Catterfeld Gwenn E. , Johnsen Devin
Published: October 2006

Are the different energy‐conserving mechanics (i.e., pendulum and spring) used in different gaits reflected in differences in energetics and/or stride parameters? The analysis included published data from several species and new data from horses. When changing from pendulum to spring mechanics, there is a change in the slope of metabolic rate (MR) vs. speed in all species, in birds and quadrupeds there is no step increase, and in humans there are conflicting reports. At the trot–gallop transition, where quadrupeds are hypothesized to change from spring mechanics to some combination of spring and pendulum mechanics, there is a change in slope of MR vs. speed in horses but not in other species. Stride frequency (SF) is a logarithmic function of walking speed in all species, a linear function of trotting/running speed, and nearly independent of speed in galloping. In humans and horses there is a discontinuity in SF at the walk–trot (run) transition but not in birds. The slope of time of contact vs. speed does not change with mechanics in most species, but it does in humans. In horses and humans, there is a discontinuity at the walk–trot (run) transition and data for other species do not permit generalization. Duty factor (DF) in humans is greater than 0.5 in walking (pendulum mechanics) and less than 0.5 when running (spring mechanics). However, this is not true in many species that have DF>0.5 at the lowest speeds where they use spring mechanics. When trotting at low speeds, horses use forelimb DF>0.5 and hind limb DF<0.5. Thus, it is confusing to distinguish between walking and running by DF. J. Exp. Zool. 305A, 2006. © 2006 Wiley‐Liss, Inc.
Dynamic coil selection for real‐time imaging in interventional MRI
Authors: Müller Sven , Umathum Reiner , Speier Peter , Zühlsdorff Sven , Ley Sebastian , Semmler Wolfhard , Bock Michael
Published: October 2006

MR‐guided intravascular interventions require image update rates of up to 10 images per second, which can be achieved using parallel imaging. However, parallel imaging requires many coil elements, which increases reconstruction times and thus compromises real‐time image reconstruction. In this study a dynamic coil selection (DCS) algorithm is presented that selects a subset of receive coils to reduce image reconstruction times. The center‐of‐sensitivity coordinates and the relative signal intensities are determined for each coil in a prescan. During the intervention m coils are selected for reconstruction using a coil ranking based on the distance to the current slice or catheter position. In a phantom experiment for m = 6, an optimal signal‐to‐background ratio (SBR) was achieved and foldover artifacts were avoided. In three animal experiments involving catheter manipulation in the aorta and the right heart chamber, the anatomy was successfully visualized at frame rates of about 5 Hz using active catheter tracking. Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.
Proton MRI as a noninvasive tool to assess elastase‐induced lung damage in spontaneously breathing rats
Authors: Quintana Harry Karmouty , Cannet Catherine , Zurbruegg Stefan , Blé François‐Xavier , Fozard John R. , Page Clive P. , Beckmann Nicolau
Published: October 2006

Elastase‐induced changes in lung morphology and function were detected in spontaneously breathing rats using conventional proton MRI at 4.7 T. A single dose of porcine pancreatic elastase (75 U/100 g body weight) or vehicle (saline) was administered intratracheally (i.t.) to male Brown Norway (BN) rats. MRI fluid signals were detected in the lungs 24 hr after administration of elastase and resolved within 2 weeks. These results correlated with perivascular edema and cellular infiltration observed histologically. Reductions in MRI signal intensity of the lung parenchyma, and increases in lung volume were detected as early as 2 weeks following elastase administration and remained uniform throughout the study, which lasted 8 weeks. Observations were consistent with air trapping resulting from emphysema detected histologically. In a separate experiment, animals were treated daily intraperitoneally (i.p.) with all‐trans‐retinoic acid (ATRA; 500 μg/kg body weight) or its vehicle (triglyceride oil) starting on day 21 after elastase administration and continuing for 12 days. Under these conditions, ATRA did not elicit a reversal of elastase‐induced lung damage as measured by MRI and histology. The present approach complements other validated applications of proton MRI in experimental lung research as a method for assessing drugs in rat models of respiratory diseases. Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.
T measurement during first‐pass contrast‐enhanced cardiac perfusion imaging
Authors: Kellman Peter , Aletras Anthony H. , Hsu Li‐yueh , McVeigh Elliot R. , Arai Andrew E.
Published: October 2006

First‐pass contrast‐enhanced (CE) myocardial perfusion imaging will experience T effects at peak concentrations of contrast agent. A reduction in the signal intensity of left ventricular (LV) blood due to T losses may effect estimates of the arterial input function (AIF) used for quantitative perfusion measurement. Imaging artifacts may also result from T losses as well as off‐resonance due to the bolus susceptibility. We hypothesized that T losses would not be significant for measurement of the AIF in full‐dose studies using a short echo time (TE = 0.6 ms). The purpose of this study was to directly measure T in the LV cavity during first‐pass perfusion. For single‐dose Gd‐DTPA (0.1 mmol/kg at 5 ml/s), the LV blood pool T had a mean value of 9 ms (N = 10) at peak enhancement. Distortion of the AIF due to T signal intensity loss will be less than 10% using TE = 0.6 ms. Magn Reson Med, 2006. Published 2006 Wiley‐Liss, Inc.
Measures of dyspnea in patients with amyotrophic lateral sclerosis
Authors: Lechtzin Noah , Lange Dale J. , Davey Cynthia , Becker Brian , Mitsumoto Hiroshi ,   HFCWO Study Group
Published: October 2006

Respiratory symptoms are not well characterized in amyotrophic lateral sclerosis (ALS). The baseline dyspnea index (BDI) and transition dyspnea index (TDI) are indices designed to measure change in dyspnea over time. They are easy to administer and do not inquire about specific physical tasks. The latter makes these scales particularly well suited for use in ALS. This study evaluated the ability of the BDI and TDI to measure dyspnea in 46 subjects with ALS. The BDI/TDI had excellent reproducibility. The TDI detected worsening dyspnea by 4 weeks and declined significantly more over the subsequent 8 weeks. The TDI was significantly associated with changes in forced vital capacity and appeared more sensitive to changes in dyspnea than the ALS functional rating scale–respiratory subscale (ALS‐FRS R) and a visual analog scale of breathlessness. The BDI and TDI thus appear to be useful measures in ALS and may have both clinical and research applications. Muscle Nerve, 2006
Disrupted galectin‐3 causes non‐alcoholic fatty liver disease in male mice
Authors: Nomoto K , Tsuneyama K , Abdel Aziz HO , Takahashi H , Murai Y , Cui Z‐G , Fujimoto M , Kato I , Hiraga K , Hsu DK , Liu F‐T , Takano Y
Published: October 2006

Galectin‐3, a β‐galactoside‐binding animal lectin, is a multifunctional protein. Previous studies have suggested that galectin‐3 may play an important role in inflammatory responses. Non‐alcoholic fatty liver disease (NAFLD) is increasingly recognized as a liver condition that may progress to end‐stage liver disease and based on the known functions of galectin‐3, it was hypothesized that galectin‐3 might play a role in the development of NAFLD. Thus, this study investigated the role of galectin‐3 in NAFLD by comparing galectin‐3 knockout (gal3−/−) mice and wild‐type (gal3+/+) mice. The livers of gal3−/− male mice at 6 months of age histologically displayed mild to severe fatty change. The liver weight per body weight ratio, serum alanine aminotransferase levels, liver triglyceride levels, and liver lipid peroxide in gal3−/− mice were significantly increased compared with those in gal3+/+ mice. Furthermore, the hepatic protein levels of advanced glycation end‐products (AGE), receptor for AGE (RAGE), and peroxisome proliferator‐activated receptor γ (PPARγ) were increased in gal3−/− mice relative to gal3+/+ mice. In conclusion, this study suggests that the absence of gal3 can cause clinico‐pathological features in male mice similar to those of NAFLD. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The presence of an intronic deletion in p73 and high levels of ZEB1 alter the TAp73/ΔTAp73 ratio in colorectal carcinomas
Authors: Domínguez G , Peña C , Silva J , García JM , García V , Rodríguez R , Cantos B , Citores MJ , España P , Bonilla F
Published: October 2006

TAp73 variants largely mimic p53 suppressor activities, while ΔTAp73 forms act as oncogenes through the inactivation of p53 and TAp73. The present study analysed how TAp73 and ΔTAp73 levels might be affected by the presence of a 73 bp deletion in a regulatory region of p73. The clinical relevance of this deletion was also examined. ZEB1 can bind to the region repressing p73 transcription in vitro. The relationship between ZEB1 and p73 variant expression levels was studied in the context of this deletion and the levels of the ZEB1 cofactors p300 and CtBP. Tumour and normal tissue from 81 colorectal cancer patients was analysed to evaluate firstly the levels of TAp73, ΔTAp73 (ΔEx2p73, ΔEx2/3p73, and ΔNp73), ZEB1, p300, and CtBP by quantitative real‐time RT‐PCR, and secondly the presence of the 73 bp deletion. Tumour characteristics were examined in each patient. Suppressor and oncogenic isoforms of p73 were co‐up‐regulated in tumour tissues. Overexpression of p73 variants was associated with adverse tumour features. The 73 bp deletion was present in 40% of the patients and was associated with adverse pathological parameters of the tumours and also with TAp73 down‐regulation. In those cases harbouring the deletion, the levels of ZEB1 and those of ΔEx2p73, ΔEx2/3p73, and ΔNp73 correlated directly. Variations in the concentration of p300 affected the observed correlations between ZEB1 and the different p73 variants. In conclusion, in colorectal cancer, the 73 bp deletion in the first intron of the p73 gene and different expression levels of ZEB1 and p300 may act in concert to affect the ratio of TAp73/ΔTAp73 forms, favouring p73 oncogenic variants. In addition, up‐regulation of p73 oncogenic isoforms predicts a poor prognosis based on its relationship with advanced tumour stage. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
SPARC and Hevin expression correlate with tumour angiogenesis in hepatocellular carcinoma
Authors: Lau CP‐Y , Poon RT‐P , Cheung S‐T , Yu W‐C , Fan S‐T
Published: October 2006

Both Secreted Protein Acidic and Rich in Cysteine (SPARC) and Hevin are multifunctional matricellular glycoproteins. Recent experimental studies suggested that Hevin and SPARC together diminish angiogenesis, but their significance in hepatocellular carcinoma (HCC) remains unclear. This study aimed to correlate SPARC and Hevin expression with angiogenesis and clinicopathological features in HCC. SPARC and Hevin protein and mRNA expression in HCC specimens were assessed by immunostaining, immunoblotting, and quantitative reverse transcriptase‐polymerase chain reaction. Tumour microvessel density (MVD) was assessed by CD34 immunostaining. The role of SPARC and Hevin in HCC was further assessed in an in vivo nude mice xenograft model. Both SPARC and Hevin mRNA levels were significantly higher in tumours than in non‐tumourous livers. A significant correlation between tumour SPARC and Hevin mRNA levels was found. Moreover, SPARC protein localized in the tumour sinusoidal area correlated significantly with Hevin protein localized in HCC cells. Truncated forms of SPARC and Hevin proteins were detected in clinical samples. Truncated SPARC protein localized in the tumour sinusoidal area correlated significantly with tumour MVD. On the other hand, overexpression of full‐length SPARC in tumour xenografts in athymic nude mice significantly delayed tumour growth, and this delay was related to a decrease in tumour angiogenesis. Expression of Hevin protein within HCC cells was related to the presence of tumour encapsulation and the absence of hepatitis B surface antigen in clinical samples. Overexpression of Hevin in tumour xenografts also significantly delayed tumour growth. In conclusion, this study has shown that SPARC and Hevin are upregulated in HCC compared with non‐tumourous liver, and that they are inter‐related at both mRNA and protein levels. Moreover, both SPARC and Hevin were related to HCC angiogenesis and tumour progression. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The impact of NSAID or COX‐2 inhibitor use on the initiation of antihypertensive therapy
Authors: Yood Marianne Ulcickas , Watkins Emmeline , Wells Karen , Kucera Gena , Johnson Christine Cole , Eva Lydick
Published: October 2006

Purpose

The objective of this study was to quantify the associations between NSAIDs and COX‐2 inhibitors and risk for initiating antihypertensive therapy.

Methods

We conducted a population‐based case‐control study in a large, integrated health system in the Midwestern United States. Cases (N = 23 562) were new users of antihypertensive therapy from 1, July 1997, through 31, January 2003. Controls (N = 23 562) were randomly selected and matched to cases on age, copay, medical care utilization, sex, and index date. The main outcome measures were exposure to NSAIDs and COX‐2 inhibitors.

Results

Recent prescription NSAID use was associated with an increased risk for initiation of antihypertensive therapy (odds ratio (OR) = 1.6, 95%CI 1.5, 1.7) as were selective COX‐2 inhibitors (OR = 1.8, 95%CI 1.6, 2.1). After adjusting for age, sex, co‐payment, race, and exposure to other NSAIDs/COX‐2, each non‐selective NSAID (diclofenac, ibuprofen, indomethacin, naproxen, oxaprozin) was associated with an increased risk of antihypertensive therapy initiation, with ORs ranging from 1.4 to 1.8. Recent users of COX‐2 inhibitors had an increased risk of initiating antihypertensive therapy, regardless of specific drug (celecoxib adjusted OR = 1.7 (95%CI 1.3, 2.1); rofecoxib adjusted OR = 1.7 (95%CI 1.4, 1.9)).

Conclusions

A consistent increased risk of initiation of antihypertensive therapy was observed among recent users of NSAIDs and COX‐2 inhibitors. Unlike previous studies, the results indicate that the effects of rofecoxib and celecoxib are equivalent. Copyright © 2006 John Wiley & Sons, Ltd.
Parents' optimism is related to their ratings of their children's behaviour
Authors: Heinonen Kati , Räikkönen Katri , Scheier Michael F. , Pesonen Anu‐Katriina , Keskivaara Pertti , Järvenpää Anna‐Liisa , Strandberg Timo
Published: October 2006

Associations between parents' dispositional optimism‐pessimism (LOT‐R) and their ratings of their children's behaviour were studied prospectively from infancy (M = 6.3, SD = 1.3 months) to middle childhood (M = 5.5, SD = 0.23 years) (n = 212). One parent's higher optimism (overall LOT‐R and component score) and/or lower pessimism (component score) at infancy predicted the same parent's own but not the other parent's ratings of the child's behaviour as less internalising and less externalising, and socially more competent and greater in self‐mastery in middle childhood, even when controlling for child's positive and negative affectivity 5 years earlier. Ratings of lower negative affectivity in their infant predicted the same parent's increasing optimism and decreasing pessimism over 5 years. The associations between parental optimism and the child's social competence and self‐mastery survived after adjustments for parental neuroticism and depressive symptoms. Neither parent nor child gender systematically moderated the associations. The current findings shed light on the developmental paths of children's positive behavioural outcomes. (n = 144). Copyright © 2006 John Wiley & Sons, Ltd.
Midlife concerns and short‐term personality change in middle adulthood
Authors: van Aken Marcel A. G. , Denissen Jaap J. A. , Branje Susan J. T. , Dubas Judith Semon , Goossens Luc
Published: October 2006

In this study, it was expected that personality change would be related to parents' concerns in various domains of midlife functioning. Personality was found to be moderately stable, but small but reliable change was also found. Fathers' change in personality was uniquely related to their life satisfaction, work stress and perceptions of the level of their adolescent children's internalising problems, but not to perceived partner support. By comparison, mothers' change in personality was only uniquely related to their life satisfaction. These results suggest that personality change in midlife is associated with the successful adaptation to midlife concerns. This pattern is consistent with social investment theories of personality development, though cross‐lagged longitudinal research is needed to substantiate this conclusion. Copyright © 2006 John Wiley & Sons, Ltd.
Photo‐ and electrochemical bonding of DNA to single crystalline CVD diamond
Authors: Shin D. , Rezek B. , Tokuda N. , Takeuchi D. , Watanabe H. , Nakamura T. , Yamamoto T. , Nebel C. E.
Published: October 2006

Alkene and nitrophenyl molecules have been covalently bonded to single crystal diamond using photochemical and electrochemical techniques. The surface density of electrochemically grafted nitrophenyl groups is about 5% of a monolayer (8 × 1013 molecules/cm2) on initially H‐terminated diamond. Covalently‐bonded nitrophenyl groups on single‐crystalline diamond are characterized to have two successive reversible one‐electron transfer reactions due to a regularly‐oriented arrangement. On oxidized surface of boron doped electrodes, a slightly (10%) smaller density is detected. Photochemical attachment of alkene molecules results also in a well arranged films as detected by angle resolved X‐ray photoelectron spectroscopy (XPS). The density of 10‐amino‐dec‐1‐ene molecules protected with trifluoroacetic acid (“TFAAD”) is calculated to be in the range 2 × 1014 molecules/cm2. The bonding mechanism of Alkene molecules to high quality hydrogen terminated single crystalline CVD diamond has been characterized using a variety of experiments which show that photo‐excited electrons of 5 eV energy trigger the photochemical attachment. The minimum time required to achieve a monolayer attachment of TFAAD molecules on (100)(2 × 1):H diamond is discussed and compared with experimental data from XPS. The benzene and alkene linker molecules are then reacted with the heterobifunctional cross linker sulphosuccinimidyl‐4‐(N‐maleimidomethyl)cyclohexane‐1‐carboxylate and finally with thiol‐modified ss‐DNA to produce a DNA‐modified diamond surface. The interaction with complementary and partially mismatched DNA is characterized by fluorescence microscopy. Microscopic properties of DNA layers on diamond have been characterized by contact‐ and oscillatory‐mode atomic force microscopy (AFM). A comparison of bonding forces, detected by contact mode AFM, reveals significant bonding strength differences. For both, electro‐ and photochemically bonded DNA, tilted molecule arrangements are detected, with angles in the range 30 ° to 46° with respect to the diamond surface. The DNA films are dense with a surface roughness of about 5 Å. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
High mobility diamonds and particle detectors
Authors: Pernegger H.
Published: October 2006

The basic properties of high‐quality CVD diamond film make them very interesting for a wide range of detectors: they are radiation hard, provide fast signals, show very low leakage current even in high radiation environments, have excellent thermal properties and can be manufactured as free‐standing detectors. This paper will give an overview of recent test results on polycrystalline and single crystal CVD diamond detectors. Large polycrystalline CVD diamonds with a charge collection distance up to 300 μm have been tested and are used to build prototype tracking detectors and beam monitors at the moment. Further irradiation studies have been carried out using a 24 GeV proton beam to test samples up to a total fluence of 1.8 × 1016 protons/cm2. Measurements on several samples of single‐crystal CVD diamonds have shown full charge collection in the detector. Results of transient‐current measurements on single crystal CVD diamonds, which are used to determine the charge carrier mobility and lifetime, show the excellent electrical properties of this material. The paper will present several different applications of CVD diamond detectors, which benefit from the recent improvements of detector‐grade diamonds. They range from tracking in High Energy Physics experiments, to high‐speed Beam Conditions Monitor at the collider experiments up to CVD diamond detectors as beam diagnostic in proton cancer therapy. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Chemical vapor deposition of homoepitaxial diamond films
Authors: Teraji Tokuyuki
Published: October 2006

This paper presents a review of state‐of‐the‐art reports of homoepitaxial diamond growth. Crystal growth and characterization methods that are commonly used for homoepitaxial diamond studies are first described briefly. Then, effects of each process parameter on the growth mode of homoepitaxial diamond are discussed. Methane concentration and substrate temperature were two dominant parameters that determine the growth rate and crystalline quality of diamond films, while conditions of diamond substrates including crystal orientation and pretreatments should be optimized for high‐quality diamond deposition. Attempts to increase growth rate of homoepitaxial diamond films while keeping their crystalline quality are discussed in the later section. Increase of microwave power density for plasma‐assisted chemical vapor deposition was found to be effective for the high‐rate growth of diamond. Free‐exciton recombination emission was intensively observed from homoepitaxial films grown at higher growth rate of 3.5 μm/h under the high power density condition. In addition, boron‐doped samples grown under the high‐power conditions showed high Hall mobility of 1620 cm2 V s−1 at room temperature. The plasma power density is thus one of the important parameters of diamond deposition from the viewpoint of electronic device application. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Ultrafast degenerate four‐wave mixing in CuCl ultrathin films
Authors: Ichimiya M. , Ashida M. , Yasuda H. , Ishihara H. , Itoh T.
Published: October 2006

Degenerate four‐wave mixing (DFWM) spectra of CuCl thin films with high crystalline quality and with thicknesses in the order of hundreds of nanometers have been investigated. We found that the several components appear with the enormous radiative shift below the transverse exciton energy in the DFWM spectrum and succeeded in demonstrating that the energy of each component is in good agreement with the eigenenergy for the mode structure of a size‐dependent exciton–radiation coupled system. The ultrafast response time of DFWM around 100 fs is observed in a thin film with a thickness of 187 nm, which reflects the theoretically predicted and extremely large radiative width. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Optical manipulation of CuCl nanoparticles under an excitonic resonance condition in superfluid helium
Authors: Inaba K. , Imaizumi K. , Katayama K. , Ichimiya M. , Ashida M. , Iida T. , Ishihara H. , Itoh T.
Published: October 2006

In order to prepare the optimal condition for the resonant optical manipulation, a lot of CuCl particles with a broad size‐distribution ranging from 10 nm to 10 μm have been directly fabricated from a bulk sample by laser ablation in superfluid helium. We irradiated these particles with the laser light covering the excitonic resonance levels of particles smaller than 100 nm in order to transport them onto a target silicon substrate by using resonant radiation force. As a result, we have observed that many particles of from 10 to 50 nm diameters adhere to the substrate. This means that these nanoparticles are transported by the resonant radiation force much stronger than the gravitational force. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Developing a Partnership Model for Cancer Screening with Community‐Based Organizations: The ACCESS Breast Cancer Education and Outreach Project
Authors: Rapkin Bruce D. , Massie Mary Jane , Jansky Elizabeth J. , Lounsbury David W. , Murphy Paulette D. , Powell Shemeeakah
Published: October 2006

There is growing enthusiasm for community‐academic partnerships to promote health in underserved communities. Drawing upon resources available at a comprehensive cancer center, we developed the ACCESS program to guide community based organizations through a flexible program planning process. Over a three‐year period, ACCESS partnered with 67 agencies serving various medically underserved populations. Organizations included hospitals, parishes, senior centers, harm reduction programs, and recreational facilities. Program outcomes at the organizational level were quantified in terms of introduction of new cancer information, referral or screening programs, as well as organizational capacity building. ACCESS represents a viable model for promoting partnership to transfer behavioral health programs and adapt interventions for new audiences. Plans to further evaluate and enhance this model to promote cancer screening efforts are discussed. We argue that, ultimately, formation and development of community partnerships need to be understood as a fundamental area of practice that must be systematically integrated into the mission of major academic medical institutions in every area of public health.
Stopped-Flow Kinetic Studies of the Interaction of Bovine Folate Binding Protein (FBP) and Folate
Authors: Christensen Ulla , Holm Jan , Hansen Steen Ingemann
Published: October 2006

The kinetics of the interaction of bovine folate binding protein and folate at pH 7.4 and 5.0 were followed by measuring the changes of the intrinsic protein fluorescence intensity using the stopped-flow technique, which enables the study of reactions from the millisecond time-range. Our results immediately reject a simple one-step binding model, which requires a linear dependence of the observed rate constant on the concentration of the ligand. Thus, we are able to conclude that at pH 5.0 the interaction occurs in two steps and at pH 7.4 in three steps. Changes of fluorescence spectra at equilibrium were used to estimate the overall binding constants. Comparative studies on the binding of folate to human albumin are also reported.
Spectrin Organization and Dynamics: New Insights
Authors: Chakrabarti Abhijit , Kelkar Devaki A. , Chattopadhyay Amitabha
Published: October 2006

Spectrin is the major constituent protein of the erythrocyte cytoskeleton which forms a filamentous network on the cytoplasmic face of the membrane by providing a scaffold for a variety of proteins. In this review, several aspects of spectrin organization are highlighted, particularly with respect to its ability to bind hydrophobic ligands and its interaction with membrane surfaces. The characteristic binding of the fluorescent hydrophobic probes Prodan and pyrene to spectrin, which allows an estimation of the polarity of the hydrophobic probe binding site, is illustrated. In addition, the contribution of uniquely localized and conserved tryptophan residues in the ‘spectrin repeats’ in these processes is discussed. A functional implication of the presence of hydrophobic binding sites in spectrin is its recently discovered chaperone-like activity. Interestingly, spectrin exhibits residual structural integrity even after denaturation which could be considered as a hallmark of cytoskeletal proteins. Future research could provide useful information about the possible role played by spectrin in cellular physiology in healthy and diseased states.