bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum Antioxidants and Skin Cancer Risk: An 8-Year Community-Based Follow-up Study
Authors: van der Pols Jolieke C. , Heinen Mirjam M. , Hughes Maria Celia , Ibiebele Torukiri I. , Marks Geoffrey C. , Green Adèle C.
Published: April 2009

Background: Antioxidant nutrients can help prevent skin damage caused by ultraviolet radiation from sunlight, but it is not clear whether serum concentrations of such nutrients influence skin cancer risk.

Methods: We carried out a prospective study of the associations between serum concentrations of antioxidant nutrients and incidence (person-based and tumor-based) of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin among a random subsample of 485 adults from an Australian community. Participants were divided into thirds, ranked according to their serum concentrations of carotenoids, α-tocopherol, and selenium measured in 1996 and were monitored for incident, histologically confirmed BCC and SCC tumors until 2004.

Results: Although there were no associations between baseline serum carotenoids or α-tocopherol concentrations and incidence of BCC or SCC, baseline serum selenium concentrations showed strong inverse associations with both BCC and SCC tumor incidence. Compared with participants with lowest selenium concentrations at baseline (0.4-1.0 μmol/L), those with the highest serum selenium concentrations (1.3-2.8 μmol/L) had a decreased incidence of BCC tumors (multivariate relative risk, 0.43; 95% confidence interval, 0.21-0.86; Ptrend = 0.02) and SCC tumors (multivariate relative risk, 0.36; 95% confidence interval, 0.15-0.82; Ptrend = 0.02).

Conclusion: Relatively high serum selenium concentrations are associated with an ∼60% decrease in subsequent tumor incidence of both BCC and SCC, whereas serum concentrations of carotenoids or α-tocopherol are not associated with later skin cancer incidence. A possible U-shaped association between serum selenium concentrations and SCC of the skin needs confirmation. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1167–73)
Sequencing of Type I Insulin-Like Growth Factor Receptor Inhibition Affects Chemotherapy Response In vitro and In vivo
Authors: Zeng Xianke , Sachdev Deepali , Zhang Hua , Gaillard-Kelly Martine , Yee Douglas
Published: April 2009

Purpose: The aim of this study was to determine the optimal sequence of combining anti-type I insulin-like growth factor receptor (IGF1R) antibodies with chemotherapeutic drugs in cancer cells in vitro and in vivo.

Experimental Design: MCF-7 and LCC6 cells were treated with subcytotoxic concentrations of doxorubicin with or without anti-IGF1R antibodies (scFv-Fc or EM164 and its humanized version AVE1642). Treatments were given simultaneously, doxorubicin followed by anti-IGF1R antibody, or anti-IGF1R antibody followed by doxorubicin, with measurement of in vitro proliferation, apoptosis, and anchorage-independent growth. The effects of sequencing on LCC6 xenograft growth and metastasis were studied.

Results: Doxorubicin followed by anti-IGF1R antibody (scFv-Fc or EM164) was the most effective combination strategy to inhibit cell monolayer growth and anchorage-independent growth. This sequential combination triggered increased poly (ADP-ribose) polymerase cleavage compared with other treatment sequences. The reverse sequence, antibody followed by doxorubicin treatment, protected cells from chemotherapy by decreasing apoptosis, arresting cells in S phase, and inhibiting the level and activity of topoisomerase IIα. Finally, our in vivo data show that recovery of IGF1R prior to doxorubicin therapy resulted in the best therapeutic responses. Low doses of AVE1642 that allowed IGF1R expression to recover at one week were more effective in combination with doxorubicin than higher antibody doses.

Conclusion: The timing of IGF1R inhibition affects responses to chemotherapy. The optimal sequence was doxorubicin followed by anti-IGF1R antibody, whereas the opposite sequence inhibited doxorubicin effects. Thus, the dose and sequencing of anti-IGF1R therapies should be considered in the design of future clinical trials.
Valproate, in Combination with Pemetrexed and Cisplatin, Provides Additional Efficacy to the Treatment of Malignant Mesothelioma
Authors: Vandermeers Fabian , Hubert Pascale , Delvenne Philippe , Mascaux Céline , Grigoriu Bogdan , Burny Arsène , Scherpereel Arnaud , Willems Luc
Published: April 2009

Purpose: Present chemotherapeutic regimens are marginally efficient in tumor cells being particularly resistant to radiotherapy and/or chemotherapy. We hypothesized that unresponsiveness of tumors to conventional therapeutic agents might be due to inappropriate gene expression resulting from epigenetic modifications and leading to transcriptional silencing. The goal of this study was to evaluate the anticancer effect of a histone deacetylase inhibitor, valproate, on mesothelioma cells in combination with pemetrexed and cisplatin, the usual first-line regimen of chemotherapy for this tumor.

Experimental Design and Results: We show that valproate augments apoptosis induced by pemetrexed and cisplatin in mesothelioma cell lines and in tumor cells from patient's biopsies. Onset of apoptosis involves both extrinsic and intrinsic pathways requiring enzymatic activities of caspases 8 and 9, respectively. Valproate but not suberoylanilide hydroxamic acid efficiently stimulates the production of reactive oxygen species. The free radical scavenger N-acetylcysteine inhibits apoptosis, indicating that reactive oxygen species are major mediators of valproate activity. As expected, valproate alone or combined with pemetrexed and cisplatin triggers hyperacetylation of histone H3. Bid protein processing in truncated t-Bid and cytochrome c release from mitochondria are significantly increased in the presence of valproate, providing a mechanistic rationale for improvement of the proapoptotic efficacy of cisplatin and pemetrexed. Finally, valproate when combined with pemetrexed and cisplatin prevents tumor growth in mouse models of epithelioid mesothelioma.

Conclusions: These observations support the potential additional efficacy of valproate in combination with pemetrexed and cisplatin for treatment of malignant mesothelioma.
A Phase I Study of a Combination of Yttrium-90–Labeled Anti–Carcinoembryonic Antigen (CEA) Antibody and Gemcitabine in Patients with CEA-Producing Advanced Malignancies
Authors: Shibata Stephen , Raubitschek Andrew , Leong Lucille , Koczywas Marianna , Williams Lawrence , Zhan Jiping , Wong Jeffrey Y.C.
Published: April 2009

Purpose: To determine the maximum tolerated dose of combined therapy using an yttrium-90–labeled anti–carcinoembryonic antigen (CEA) antibody with gemcitabine in patients with advanced CEA-producing solid tumors.

Experimental Design: The chimeric human/murine cT84.66 is an anti-CEA intact IgG1, with high affinity and specificity to CEA. This was given at a fixed yttrium-90–labeled dose of 16.6 mCi/m2 to subjects who had and an elevated CEA in serum or in tumor by immunohistochemistry. Also required was a tumor that imaged with an 111In-labeled cT84.66 antibody. Patients were treated with escalating doses of gemcitabine given i.v. over 30 minutes on day 1 and 3 after the infusion of the yttrium-90–labeled antibody. Patients were treated in cohorts of 3. The maximum tolerated dose was determined as the highest level at which no >1 of 6 patients experienced a dose limiting toxicity.

Results: A total of 36 patients were enrolled, and all but one had prior systemic therapy. The maximum tolerated dose of gemcitabine in this combination was 150 mg/m2. Dose limiting toxicities at a gemcitabine dose of 165 mg/m2 included a grade 3 rash and grade 4 neutropenia. One partial response was seen in a patient with colorectal cancer, and 4 patients had a >50% decrease in baseline CEA levels associated with stable disease. Human antichimeric antibody responses were the primary reason for stopping treatment in 12 patients.

Conclusions: Feasibility of combining gemcitabine with an yttrium-90–labeled anti-CEA antibody is shown with preliminary evidence of clinical response.
Circulating Osteoprotegerin and sRANKL Concentrations in the Perinatal Period at Term
Authors: Briana Despina D. , Boutsikou Maria , Baka Stavroula , Hassiakos Demetrios , Gourgiotis Demetrios , Malamitsi-Puchner Ariadne
Published: April 2009

Background: Intrauterine growth restriction (IUGR) has been associated with low bone mass in infancy and increased risk for osteoporosis development in adult life. Osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) are main determinants of bone resorption. Objectives: To investigate OPG and soluble RANKL (sRANKL) concentrations in maternal, fetal and neonatal serum of IUGR patients and appropriate for gestational age (AGA) pregnancies. Additionally, plasma intact parathormone (PTH) concentrations were evaluated. Methods: Circulating OPG, sRANKL and PTH concentrations were measured in 40 mothers and their singleton full-term fetuses-neonates (AGA: n = 20, and IUGR: n =20) on postnatal days 1 (N1) and 4 (N4). Results: No significant differences in OPG, sRANKL or PTH concentrations were observed between AGA and IUGR groups. In both groups, maternal OPG concentrations were elevated compared with fetal, and N1 and N4 concentrations (p ≤ 0.045 in all cases). N4 sRANKL concentrations were elevated compared with maternal, fetal and N1 ones (p ≤ 0.01 in all cases). Fetal and N1 sRANKL concentrations correlated positively with PTH levels (r = 0.642, p = 0.024 and r = 0.584, p = 0.046, respectively). Conclusions: The lack of a difference in circulating OPG, sRANKL or PTH concentrations between IUGR cases and AGA controls suggests that the low bone mass of IUGR infants may not be related to higher bone resorption rates. The increased maternal, compared with fetal/neonatal, OPG concentrations may suggest their placental origin. The lower OPG and higher sRANKL concentrations in fetuses and neonates could represent high bone resorption rates.
The Effect of Different Fluoride Concentrations and pH of Dentifrices on Plaque and Nail Fluoride Levels in Young Children
Authors: Buzalaf M.A.R. , Vilhena F.V. , Iano F.G. , Grizzo L. , Pessan J.P. , Sampaio F.C. , Oliveira R.C.
Published: April 2009

To evaluate the influence of dentifrice pH and fluoride (F) concentration on F uptake by plaque and nails, two sets of 5- to 6-year-old children were randomly allocated into four groups, according to the type of dentifrice they had been using for 1 year: (1) experimental liquid dentifrice (ELD), 1,100 ppm F, pH 7.0; (2) ELD, 1,100 ppm F, pH 4.5; (3) ELD, 550 ppm F, pH 4.5, and (4) commercial toothpaste, 1,100 ppm F, pH 7.0. In one set of children, nails were clipped. In the second, plaque samples were collected 1 h after the last use of dentifrice. F concentration in plaque and nails was analyzed. Plaque F concentration was significantly lower in group 4 than in groups 1–3. Nail F concentration was significantly higher in group 4, and significantly lower in group 3, than in group 1 or 2. Plaque F uptake was influenced significantly by dentifrice consistency and nonsignificantly by pH and F concentration. Reduction of dentifrice pH did not affect nail F concentration.
National Pathfinder Survey on Children’s Oral Health in Italy: Pattern and Severity of Caries Disease in 4-Year-Olds
Authors: Campus G. , Solinas G. , Strohmenger L. , Cagetti M.G. , Senna A. , Minelli L. , Majori S. , Montagna M.T. , Reali D. , Castiglia P.
Published: April 2009

This paper describes the dental health status of Italian 4-year-olds in 2004/2005 and analyzes the association between caries in preschool children and some background characteristics in children and parents. Caries was recorded according to WHO criteria. 5,538 subjects were examined. Information on the children’s and their parents’ social, behavioral, ethnic and demographic status was obtained through a series of closed questions. Bivariate analysis was performed to investigate the association between caries and background characteristics. The probability of being an extra zero for the dmfs index was estimated via the zero-inflated negative binomial regression model (ZINB). 78.4% (95% CI = 77.2–79.6) of the children were caries-free. The national mean dmfs index was 1.36 (95% CI = 1.15–1.57), ranging from 1.22 (95% CI = 1.03–1.42) in the Italian North-East to 1.73 (95% CI = 0.83–2.63) in the South section. Significant bivariate associations between caries experience and risk factors were observed for parents’ nationality (not Italian vs. Italian: p < 0.001), parents’ educational levels (low vs. high: p < 0.001), preterm birth (yes vs. no: p = 0.011), prolonged breastfeeding (≤13 months vs. >13 months: p = 0.038) and early tooth eruption (<6 months as reference: p = 0.004). Multivariable analysis (ZINB) showed that children with a low caries risk level had a higher probability of being an extra zero; in particular, children from fathers with a high educational level showed a probability of being an extra zero of 0.22. The results suggest a need to plan preventive programs to reduce oral health disparities among Italian preschool children, based on educational intervention with parents and children concerning oral health and caries prevention.
The Study of the Composites Fabric’s Shaping using an Augmented Lagrangian Approach
Authors: Cherouat A. , Radi B. , El Hami A.
Published: April 2009

In this paper, we are interested in the forming of composite part by deep‐drawing and laying‐up processes. We present a new finite element model for the simulation of these processes. The augmented Lagrangian approach is adopted to treat the frictional contact between the composite fabric and the tools. It is based on a new way of writing the Coulomb’s friction law. The numerical simulation is carried out with Abaqus/Explicit software and some numerical results are given to validate the proposed numerical method.
A Review of the Application of C/SiC Composite in Thermal Protection System
Authors: Zhang Qingmao , Li Guansheng
Published: April 2009

This study reviews the application of the C/SiC composites in the thermal protection systems (TPS). Special attention is put on the structure design and optimization of the C/SiC shell panel. The comparisons of several TPS show that the ceramic matrix composite (CMC) is one of the most potential materials for TPS. The crucial role of multi‐disciplinary design and optimization is pointed out in the future design of C/SiC thermal protection structure. This review provides a guideline on the current and future study of C/SiC thermal protection structure.
Proactive and Reactive Aggression in a Child Psychiatric Inpatient Population
Authors: Fite Paula J. , Stoppelbein Laura , Greening Leilani
Published: April 2009

The study examined relations between caregiver- and child-reported proactive and reactive aggression and psychopathic characteristics (callous/unemotional traits, narcissism, and impulsivity) in a sample of 105 children (69% male) ranging from 6 to 12 years of age ( M = 9.61, SD = 1.83) who were admitted to a child psychiatric inpatient facility. Caregiver reports of aggression suggested that proactive and reactive aggression were similarly related to callous/unemotional traits and narcissism but that only reactive aggression was associated with impulsivity. In contrast, child reports of proactive aggression, but not reactive aggression, were associated with all three psychopathic characteristics. Theoretical and clinical implications are discussed.
Assessment of Community Reintegration Planning for Sex Offenders
Authors: Willis Gwenda M. , Grace Randolph C.
Published: April 2009

Poor planning for reintegrating child molesters from prison to the community is a likely risk factor for sexual recidivism. The quality of reintegration planning was retrospectively measured for groups of recidivist ( n = 30) and nonrecidivist ( n = 30) child molesters who were individually matched on static risk level and time since release. Recidivists had significantly poorer reintegration planning scores than nonrecidivists, consistent with a previous study by the authors. Data from both studies were combined (total N = 141), and survival analyses showed that poor reintegration planning predicted an increased rate of recidivism. Accommodation, employment, and social support planning combined to predict recidivism, with predictive validity comparable to static risk models (area under the curve = .71). Summing these items yielded a scale of reintegration planning quality that differentiated well between recidivists and nonrecidivists and may have practical utility for risk assessment as an adjunct to static models.
Resource utilisation and costs of palliative cancer care in an interdisciplinary health care model
Authors: Johnson AP , Abernathy T , Howell D , Brazil K , Scott S
Published: April 2009

This paper presents a detailed description of health care resource utilisation and costs of a pilot interdisciplinary health care model of palliative home care in Ontario, Canada. The descriptive evaluation entailed examining the use of services and costs of the pilot program: patient demographics, length of stay broken down by disposition (discharged, alive, death), access to services/resources, use of family physician and specialist services, and drug use. There were 434 patients included in the pilot program. Total costs were approximately CAN$2.4 million, and the cost per person amounted to approximately CAN$5586.33 with average length of stay equal to over 2 months (64.22 days). One may assume that length of stay would be influenced by the amount of service and support available. Future research might investigate whether in-home palliative home care is the most cost effective and suitable care setting for those patients requiring home care services for expected periods of time.
NK1 receptor antagonism and emotional processing in healthy volunteers
Authors: Chandra P. , Hafizi S. , Massey-Chase RM , Goodwin GM , Cowen PJ , Harmer CJ
Published: April 2009

The neurokinin-1 (NK 1) receptor antagonist, aprepitant, showed activity in several animal models of depression; however, its efficacy in clinical trials was disappointing. There is little knowledge of the role of NK1 receptors in human emotional behaviour to help explain this discrepancy. The aim of the current study was to assess the effects of a single oral dose of aprepitant (125 mg) on models of emotional processing sensitive to conventional antidepressant drug administration in 38 healthy volunteers, randomly allocated to receive aprepitant or placebo in a between groups double blind design. Performance on measures of facial expression recognition, emotional categorisation, memory and attentional visual-probe were assessed following the drug absorption. Relative to placebo, aprepitant improved recognition of happy facial expressions and increased vigilance to emotional information in the unmasked condition of the visual probe task. In contrast, aprepitant impaired emotional memory and slowed responses in the facial expression recognition task suggesting possible deleterious effects on cognition. These results suggest that while antagonism of NK1 receptors does affect emotional processing in humans, its effects are more restricted and less consistent across tasks than those of conventional antidepressants. Human models of emotional processing may provide a useful means of assessing the likely therapeutic potential of new treatments for depression.
Multitrait-Multimethod Analysis of FCAT Reading and Writing
Authors: Shermis Mark D. , Long Susanne K.
Published: April 2009

This study investigated the convergent and discriminant validity of the high-stakes Florida Comprehensive Assessment Test (FCAT) in both reading and writing at grade levels 4, 8, and 10. The data from the 2006 FCAT administration were analyzed via traditional multitrait-multimethod (MTMM) analysis to identify the factor structure and structural equation models (SEMs), to determine the weights of the influential variables underlying the tests. The MTMM analyses suggested that across all grade levels, the correlation between the multiple-choice reading and multiple-choice writing tests of the FCAT approached the reliability coefficients for each test separately. These correlations were higher than the correlations between the multiple choice and performance sections for each trait. The SEM analyses, however, provided support for both the convergent and discriminant validity of the test scores. The fit for the SEMs improved from a CFI of .84 for 4th graders (a poor fit) to .97 for 10th-grade students.
Does Physical Therapy Improve Outcome in Infants with Joint Hypermobility and Benign Hypotonia?
Authors: Mintz-Itkin Rina , Lerman-Sagie Tally , Zuk Luba , Itkin-Webman Taly , Davidovitch Michael
Published: April 2009

This study examined the effect of the frequency of physical therapy on the outcome of infants referred for delayed motor development due to joint hypermobility and benign hypotonia. The study groups comprised 29 infants (8-12 months) who were randomly placed into a monthly and weekly treatment groups. No difference was found between the 2 study group scores on the different tests at all assessment points. However, assessment of walking at the age of 15 months revealed a clear advantage of the infants who were treated weekly. Our study demonstrated a minor benefit of weekly treatment protocol only in the achievement of independent walking in children with joint hypermobility and benign hypotonia. It did not prove an advantage of weekly physical therapy. It seems that monthly physical therapy combined with a home treatment protocol implemented by the primary caregivers is sufficient to achieve motor catch-up.
Effect of Hospital Practices on Breastfeeding: A Survey in the Italian Region of Lazio
Authors: Asole Simona , Spinelli Angela , Antinucci Laura Ellen , Di Lallo Domenico
Published: April 2009

To investigate hospital practices associated with infant feeding during hospital stay and at 1 month of age, all women who were in 17 maternity hospitals on a given day and had delivered a singleton newborn were contacted. Of the 165 eligible women, 153 participated in the survey. Data were collected from the mothers' clinical records and through interview. Odds ratios were calculated to estimate the effect of hospital practices on breastfeeding rates. The main findings are that cesarean section (adjusted odds ratio [ORadj] = 3.69; 95% confidence interval [CI], 1.19-11.47), lack of information about the advantages of breastfeeding (ORadj = 4.78; 95% CI, 1.50-15.26), and absence or partial absence of rooming-in (ORadj = 14.64; 95% CI, 2.24-95.75) increase the risk of complementary breastfeeding during hospital stay. In turn, complementary breastfeeding during hospital stay was the major factor associated with not breastfeeding at 1 month of age (ORadj = 6.35; 95% CI, 2.52-16.01). These findings suggest that some hospital practices might have a negative effect on the initiation and continuation of breastfeeding. J Hum Lact. 25(3):333-340.
Activist trust: the diffusion of green expertise in a Brazilian landscape
Authors: Delgado Ana
Published: April 2009

MST (Movimento Sem Terra/Landless People’s Movement) is the largest rural movement of Latin America. Since the late 1990s, it has taken part in the diffusion of expertise about biodiversity conservation. Using an ethnographic approach, this paper investigates sources and roles of trust within this process. How does trust work when experts and laypeople belong to the same movement? The paper uses and critically discusses the works of Brian Wynne and the Actor Network Theory. It describes the particular ways in which the building of trust takes place within the intimate networks of MST. As ecological expertise becomes a central element within MST’s project of liberation, the sources of trust are both affective and effective. Interests, social recognition and identity are intertwined. In the conclusion, I propose the concept of activist trust.
Increased Prevalence of Antiheparin Platelet Factor 4 Antibodies in Patients May Be Due to Contaminated Heparin
Authors: Adiguzel Cafer , Bansal Vinod , Litinas Evangelos , Cunanan Josephine , Iqbal Omer , Nelson Kelly , Kannan Meganathan , Hoppensteadt Debra , Fareed Jawed
Published: April 2009

During the period of November 2007 to January 2008, an increased prevalence of adverse reactions to heparin was noted. These adverse events have been attributed to the presence of purposeful contaminant, oversulfated chondroitin sulfate (OSCS) from April 2007 to May 2008. An analysis of dialysis patients' plasma obtained in 2006 and 2007 consistently had a low (5%) prevalence of AHPF4 antibodies. Blood samples from 78 patients on maintenance hemodialysis, who were potentially exposed to OSCS-contaminated heparin, were analyzed for the presence of all AHPF4 antibodies using a commercially available ELISA kit from GTI. Although there was no change in the platelet count of these patients, 15 of 78 patients (19.2%) studied had an increased prevalence of AHPF4 antibodies. Subtyping of the all platelet factor 4 (PF4) antibodies documented showed a higher prevalence of immunoglobulin G antibodies as compared to their previously determined antibodies. These observations suggest that the OSCS contaminant in the recalled heparin triggers an immunogenic response not seen with OSCS-contaminated free heparin.
A Cybernetic Model of Global Personality Traits
Authors: Van Egeren Lawrence F.
Published: April 2009

Neurobehavioral studies of human and animal temperament have shed light on how individual personality traits influence human actions. This approach, however, leaves open questions about how the entire system of traits and temperaments function together to exercise control. To address this key issue, I describe a cybernetic model of control and then apply it to the Big Five (B5) personality traits. Employing evidence from descriptive trait terms, temperamental behavioral processes associated with traits, and empirical correlates of traits, I relate distinct cybernetic processes of self-regulation to the B5 traits. The B5 traits broadly parallel basic cybernetic self-regulation processes. For example, the core behavior activation property of the B5 Extraversion trait can be mapped onto the device output function of automated cybernetic control systems. Implications and limitations of interpreting personality traits in self-regulation terms are discussed.
Design of Web Questionnaires: The Effects of the Number of Items per Screen
Authors: Toepoel Vera , Das Marcel , Van Soest Arthur
Published: April 2009

This article analyzes the effects of an experimental manipulation of the number of items per screen in a Web survey with forty questions aimed at measuring arousal. The authors consider effects on survey answers, item nonresponse, interview length, and the respondents' evaluation of several aspects of the survey (such as layout). Four different formats are used, with one, four, ten, and forty items and headers on a screen. The authors find no effect of format on the arousal index, but nonresponse increases with the number of items appearing on a single screen. Having multiple items on a screen shortens the duration of the interview but negatively influences the respondent's evaluation of the questionnaire layout. Grouping effects are generally similar for different demographic groups, though there are some differences in magnitude and significance level.
Accessibility and partner number of protein residues, their relationship and a webserver, ContPlot for their display
Authors: Pal Arumay , Bahadur Ranjit Prasad , Ray Partha Sarathi , Chakrabarti Pinak
Published: April 2009

Background

Depending on chemical features residues have preferred locations – interior or exterior – in protein structures, which also determine how many other residues are found around them. The close packing of residues is the hallmark of protein interior and protein-protein interaction sites.

Results

The average values of accessible surface area (ASA) and partner number (PN, the number of other residues within a distance of 4.5 Å from any atom of a given residue) of different residues have been determined and a webserver, ContPlot has been designed to display these values (relative to the average values) along the protein sequence. This would be useful to visually identify residues that are densely packed, or those involved in protein-protein interactions. The skewness observed in the distribution of PNs is indicative of the hydrophobic or hydrophilic nature of the residue. The variation of ASA with PN can be analytically expressed in terms of a cubic equation. These equations (one for each residue) can be used to estimate the ASA of a polypeptide chain using the PNs of the individual residues in the structure.

Conclusion

The atom-based PNs (obtained by counting surrounding atoms) are highly correlated to the residue-based PN, indicating that the latter can adequately capture the atomic details of packing. The average values of ASA and PN associated with each residue should be useful in protein structure prediction or fold-recognition algorithm. ContPlot would provide a handy tool to assess the importance of a residue in the protein structure or interaction site.
ProtSA: a web application for calculating sequence specific protein solvent accessibilities in the unfolded ensemble
Authors: Estrada Jorge , Bernadó Pau , Blackledge Martin , Sancho Javier
Published: April 2009

Background

The stability of proteins is governed by the heat capacity, enthalpy and entropy changes of folding, which are strongly correlated to the change in solvent accessible surface area experienced by the polypeptide. While the surface exposed in the folded state can be easily determined, accessibilities for the unfolded state at the atomic level cannot be obtained experimentally and are typically estimated using simplistic models of the unfolded ensemble. A web application providing realistic accessibilities of the unfolded ensemble of a given protein at the atomic level will prove useful.

Results

ProtSA, a web application that calculates sequence-specific solvent accessibilities of the unfolded state ensembles of proteins has been developed and made freely available to the scientific community. The input is the amino acid sequence of the protein of interest. ProtSA follows a previously published calculation protocol which uses the Flexible-Meccano algorithm to generate unfolded conformations representative of the unfolded ensemble of the protein, and uses the exact analytical software ALPHASURF to calculate atom solvent accessibilities, which are averaged on the ensemble.

Conclusion

ProtSA is a novel tool for the researcher investigating protein folding energetics. The sequence specific atom accessibilities provided by ProtSA will allow obtaining better estimates of the contribution of the hydrophobic effect to the free energy of folding, will help to refine existing parameterizations of protein folding energetics, and will be useful to understand the influence of point mutations on protein stability.
Norepinephrine transport-mediated gene expression in noradrenergic neurogenesis
Authors: Hu Yao Fei , Caron Marc G , Sieber-Blum Maya
Published: April 2009

Background

We have identified a differential gene expression profile in neural crest stem cells that is due to deletion of the norepinephrine transporter (NET) gene. NET is the target of psychotropic substances, such as tricyclic antidepressants and the drug of abuse, cocaine. NET mutations have been implicated in depression, anxiety, orthostatic intolerance and attention deficit hyperactivity disorder (ADHD). NET function in adult noradrenergic neurons of the peripheral and central nervous systems is to internalize norepinephrine from the synaptic cleft. By contrast, during embryogenesis norepinephrine (NE) transport promotes differentiation of neural crest stem cells and locus ceruleus progenitors into noradrenergic neurons, whereas NET inhibitors block noradrenergic differentiation. While the structure of NET und the regulation of NET function are well described, little is known about downstream target genes of norepinephrine (NE) transport.

Results

We have prepared gene expression profiles of in vitro differentiating wild type and norepinephrine transporter-deficient (NETKO) mouse neural crest cells using long serial analysis of gene expression (LongSAGE). Comparison analyses have identified a number of important differentially expressed genes, including genes relevant to neural crest formation, noradrenergic neuron differentiation and the phenotype of NETKO mice. Examples of differentially expressed genes that affect noradrenergic cell differentiation include genes in the bone morphogenetic protein (BMP) signaling pathway, thePhox2bbinding partnerTlx2, the ubiquitin ligasePraja2, and the inhibitor of Notch signaling,Numbl. Differentially expressed genes that are likely to contribute to the NETKO phenotype include dopamine-β-hydroxylase (Dbh), tyrosine hydroxylase (Th), the peptide transmitter 'cocaine and amphetamine regulated transcript' (Cart), and the serotonin receptor subunitHtr3a. Real-time PCR confirmed differential expression of key genes not only in neural crest cells, but also in the adult superior cervical ganglion and locus ceruleus. In addition to known genes we have identified novel differentially expressed genes and thus provide a valuable database for future studies.

Conclusion

Loss of NET function during embryonic development in the mouse deregulates signaling pathways that are critically involved in neural crest formation and noradrenergic cell differentiation. The data further suggest deregulation of signaling pathways in the development and/or function of the NET-deficient peripheral, central and enteric nervous systems.
Endogenous avidin biotin activity (EABA) in thyroid pathology: immunohistochemical study
Authors: Nikiel Barbara , Chekan Mykola , Jarząb Michal , Lange Dariusz
Published: April 2009

Background

Immunohistochemical methods based on the high affinity of avidin and biotin (e.g. ABC, LSAB) are characterized by high sensitivity and are widely used for detection of immunologic reaction. However, a non-specific reaction, observed in frozen tissues and in paraffin-embedded material, increasing after heat induced epitope retrieval (HIER), and caused either by endogenous biotin or any another chemical compound with high affinity for avidin, may lead to diagnostic mistakes. The aim of our investigation is to study presence of endogenous avidin biotin activity (EABA) in thyrocytes originating from various thyroid pathological lesions (neoplastic and non-neoplastic).

Materials and methods

The immunohistochemical study was performed on paraffin-embedded specimens of surgically resected thyroid tissue from 97 patients with thyroid diseases: 65 patients with papillary carcinoma (PTC), 11 patients with nodular goiter in whom features of benign papillary hyperplasia were found, 9 with lymphocytic thyroiditis (LT), 8 with follicular adenoma, and 4 patients with follicular carcinoma. In PTC immunohistochemical study was performed both in primary tumors and in lymph node metastases. After HIER, incubation with streptavidin from LSAB+ (DakoCytomation) kit was done.

Results

Strong cytoplasmic EABA was observed in 56 of 65 (87.5%) PTC and in oxyphilic cells in 8 of 9 cases of LT. Significant correlation between EABA in primary PTC tumor and EABA in lymph node metastases was stated. Normal surrounding thyroid tissues showed absence or weak EABA. Aberrant intranuclear localization of biotin was noted in morules of cribriform-morular variant of PTC. No statistically significant correlation between patient's age, sex, metastases presence and EABA was observed.

Conclusion

Among thyroid lesions, false positive reactions are highly probable in papillary thyroid carcinoma and in lymphocytic thyroiditis if immunohistochemical detection is used on systems containing (strept)avidin. The most probable reason is the high endogenous biotin content.
Novel Relationships of Age, Visceral Adiposity, Insulin-Like Growth Factor (IGF)-I and IGF Binding Protein Concentrations to Growth Hormone (GH) Releasing-Hormone and GH Releasing-Peptide Efficacies in Men during Experimental Hypogonadal Clamp
Authors: Veldhuis Johannes D. , Keenan Daniel M. , Bailey Joy N. , Adeniji Adebordurin M. , Miles John M. , Bowers Cyril Y.
Published: April 2009

Background: Sex steroids influence GH secretion in complex ways.

Hypothesis: Analyses in a low sex-steroid milieu will help unveil the effects of age and other nonsteroidal regulators on GH secretion.

Context: The study was conducted in a tertiary medical center.

Subjects: The study group included 13 healthy young men and 12 healthy older men.

Methods: We used GnRH agonist-induced down-regulation of testosterone and estradiol secretion, followed by consecutive infusion of l-arginine and GHRH or GHRP-2, to test secretagogue efficacies.

Outcomes: We measured basal and pulsatile GH secretion.

Results: During experimental testosterone/estradiol deprivation, older (57 ± 1.7 yr) men maintained: 1) 6.8-fold less pulsatile GH secretion (P < 0.001); and 2) 2-fold lower maximal GH responses to GHRH (P = 0.0065) and GHRP-2 (P = 0.022) than young (23 ± 1.1 yr old) individuals. Stepwise forward-selection regression analyses identified: 1) abdominal visceral fat as a dominant negative predictor of both GHRH (R2 = 0.49; P = 0.001) and GHRP-2 (R2 = 0.38; P = 0.005) efficacies; and 2) fasting IGF-I concentration as a major positive correlate of GHRH (R2 = 0.52; P < 0.001) and GHRP-2 (R2 = 0.31; P = 0.018) efficacies. Unstimulated pulsatile GH secretion was jointly correlated with IGF-I and IGFBP-3 (P = 0.039).

Conclusion: Measures of body composition (abdominal visceral fat) and pulsatile GH action (IGF-I) explain up to one half of interindividual variability in the efficacies of GHRH and GHRP-2 in sex steroid-depleted men. Accordingly, normative ranges for maximal single peptide-stimulated GH secretion in short-term hypogonadal states should incorporate the influence of these determinants as well as age.
Copper transport into the secretory pathway is regulated by oxygen in macrophages
Authors: White Carine , Kambe Taiho , Fulcher Yan G. , Sachdev Sherri W. , Bush Ashley I. , Fritsche Kevin , Lee Jaekwon , Quinn Thomas P. , Petris Michael J.
Published: April 2009

Copper is an essential nutrient for a variety of biochemical processes; however, the redox properties of copper also make it potentially toxic in the free form. Consequently, the uptake and intracellular distribution of this metal is strictly regulated. This raises the issue of whether specific pathophysiological conditions can promote adaptive changes in intracellular copper distribution. In this study, we demonstrate that oxygen limitation promotes a series of striking alterations in copper homeostasis in RAW264.7 macrophage cells. Hypoxia was found to stimulate copper uptake and to increase the expression of the copper importer, CTR1. This resulted in increased copper delivery to the ATP7A copper transporter and copper-dependent trafficking of ATP7A to cytoplasmic vesicles. Significantly, the ATP7A protein was required to deliver copper into the secretory pathway to ceruloplasmin, a secreted copperdependent enzyme, the expression and activity of which were stimulated by hypoxia. However, the activities of the alternative targets of intracellular copper delivery, superoxide dismutase and cytochrome c oxidase, were markedly reduced in response to hypoxia. Collectively, these findings demonstrate that copper delivery into the biosynthetic secretory pathway is regulated by oxygen availability in macrophages by a selective increase in copper transport involving ATP7A.
Homophilic and heterophilic polycystin 1 interactions regulate E-cadherin recruitment and junction assembly in MDCK cells
Authors: Streets Andrew J. , Wagner Bart E. , Harris Peter C. , Ward Christopher J. , Ong Albert C. M.
Published: April 2009

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited human renal disease and is caused by mutations in two genes, PKD1 (85%) and PKD2 (15%). Cyst epithelial cells are characterised by a complex cellular phenotype including changes in proliferation, apoptosis, basement membrane composition and apicobasal polarity. Since polycystin 1 (PC1), the PKD1 protein, has been located in the basolateral membrane of kidney epithelial cells, we hypothesised that it might have a key role in mediating or stabilising cell-cell interactions. In non-ciliated L929 cells, stable or transient surface expression of the PC1 extracellular domain was sufficient to confer an adhesive phenotype and stimulate junction formation. In MDCK cells, we found that PC1 was recruited to the lateral membranes coincident with E-cadherin within 30 minutes after a `calcium switch'. Recruitment of both proteins was significantly delayed when cells were treated with a PC1 blocking antibody raised to the PKD domains. Finally, PC1 and E-cadherin could be coimmunoprecipitated together from MDCK cells. We conclude that PC1 has a key role in initiating junction formation via initial homophilic interactions and facilitates junction assembly and the establishment of apicobasal polarity by E-cadherin recruitment.
The Assesment for CO2 Sequestration Potential by Magnesium silicate Minerals in Turkey: Cases of Orhaneli-Bursa and Divrigi-Sivas Regions
Authors: Baris K. , Ozarslan A. , Sahin N.
Published: April 2009

This paper examines the CO2 sequestration potential of magnesium silicate minerals in Turkey for two example cases, the Orhaneli-Bursa and Divrigi-Sivas regions. The distribution and properties of the silicate mineral deposits are provided and the quantities of CO2 that can be sequestered in these deposits is estimated. The silicate minerals in the Orhaneli and Divrigi deposits provide significant CO2 sequestration capacity. Assuming 100% mineral carbonation efficiency, approximately 2.4 million tons/year of olivine and 6.5 million tons/year of serpentine would be required to sequester the CO2 released by the power plants investigated in this study. Although more detailed studies are needed, it is concluded that this approach has potential given Turkey's large dunite (olivine) and serpentine reserves. Furthermore, the proximity of these deposits and active open-pit mines to thermal power plants emitting CO2 facilitate the utilization of mineral carbonation.
Molecular organization and recognition properties of amphiphilic cyclodextrins
Authors: de Rossi Rita H. , Silva O. Fernando , Vico Raquel V. , Gonzalez Carlos J.
Published: April 2009

The continuing challenge of using cyclodextrins (CDs) for solubilization and drug targeting has led to the preparation of a wide variety of chemically modified derivatives in order to improve the properties of these host molecules. A possible approach for pharmaceutical applications would be to combine the recognition specificity of CDs with the transport properties of organized structures such as vesicles, liposomes, or micelles. Amphiphilic CDs can be admixed to phospholipid monolayers and to liposomes, and they can be dispersed into nanospheres showing promising properties for drug encapsulation. Monoacylated derivatives of β-CD, Mod-CD (Cn), were synthesized in our laboratory from the reaction of alkenyl succinic anhydride with β-CD. We found that the compound with 10 carbon atoms in the alkenyl chain, Mod-CD (C10), can be incorporated into inverted micelles. We studied their properties in solution and at the air-water interface. In solution they have very low critical micellar concentration, and in the aggregates there are two recognition sites: one is the cavity of the CD and the other is formed by the hydrophobic tails. The alkenyl chain interacts with the cavity, but this is not an obstacle for the association with external guests such as 1-amino adamantane, phenolphthalein, or Prodan. Mod-CD (Cn) with n equal to 10, 14, and 16 (n indicates the number of carbons in the alkenyl chain), form stable monolayers at the air-water interface and they adopt an organization very different from those found for persubstituted CDs. The differences are attributed to the higher conformational flexibility of these compounds, which allows the organization of the CD units with the cavity perpendicular to the interface.
Photochemical routes to silver and gold nanoparticles
Authors: Scaiano Juan C. , Billone Paul , Gonzalez Carlos M. , Marett Luca , Marin M. Luisa , McGilvray Katherine L. , Yuan Nathan
Published: April 2009

The photochemistry of aromatic ketones through the Norrish type I cleavage of benzoins and via photoreduction generates ketyl radicals that readily reduce many metal ions, including silver and gold. Reduction to Au(0) and Ag(0) leads to the spontaneous formation of nanoparticles (NPs) in aqueous or micellar solutions. Careful consideration of kinetic factors to minimize triplet quenching by metal ions can lead to rapid NP generation. These materials are quite stable and have interesting reactivities due to the essentially unprotected characteristics of the surface.
Understanding solvation
Authors: El Seoud Omar A.
Published: April 2009

The effects of solvents on different chemical phenomena, including reactivity, spectroscopic data, and swelling of biopolymers can be rationalized by use of solvatochromic probes, substances whose UV-vis spectra, absorption, or emission are sensitive to the properties of the medium. Thermo-solvatochromism refers to the effect of temperature on solvatochromism. The study of both phenomena sheds light on the relative importance of the factors that contribute to solvation, namely, properties of the probe, those of the solvent (acidity, basicity, dipolarity/polarizability, and lipophilicity), and the temperature. Solvation in binary solvent mixtures is complex because of "preferential solvation" of the probe by one component of the mixture. A recently introduced solvent exchange model is based on the presence in the binary solvent mixture of the organic component (molecular solvent or ionic liquid), S, water, W, and a 1:1 hydrogen-bonded species (S-W). Solvation by the latter is more efficient than by its precursor solvents, due to probe-solvent hydrogen-bonding and hydrophobic interactions; dimethyl sulfoxide (DMSO)-W is an exception. Solvatochromic data are employed in order to explain apparently disconnected phenomena, namely, medium effect on the pH-independent hydrolysis of esters,1H NMR data of water-ionic liquid (IL) mixtures, and the swelling of cellulose.
An Oligovascular Niche: Cerebral Endothelial Cells Promote the Survival and Proliferation of Oligodendrocyte Precursor Cells
Authors: Arai Ken , Lo Eng H.
Published: April 2009

We show that cerebral endothelial cells secrete trophic factors that support the survival and proliferation of rat oligodendrocyte precursor cells (OPCs). This OPC-supportive phenomenon was mediated by Akt and Src signaling pathways. Noncytotoxic levels of oxidative stress downregulate trophic factor production and disrupt the ability of cerebral endothelial cells to support OPCs. These data suggest that a novel oligovascular niche may be important for sustaining oligodendrocyte renewal and homeostasis in mammalian brain.