bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patients' explanations for depression: a factor analytic study
Authors: Budd Rick , James Darren , Hughes Ian 
Published: February 2008

AbstractObjectives: Previous questionnaire studies have attempted to explore the factor structure of lay beliefs about the causes of depression. These studies have tended to either fail to sample the full range of possible causal explanations or extract too many factors, thereby producing complex solutions. The main objective of the present study was to obtain a more complete and robust factor structure of lay theories of depression while more adequately sampling from the full range of hypothesized causes of depression. A second objective of the study was to explore the relationship between respondents' explanations for depression and their perceptions of the helpfulness of different treatments received. Method and design: A 77‐item questionnaire comprising possible reasons for ‘why a person might get depressed’ was mailed out to members of a large self‐help organization. Also included was a short questionnaire inviting respondents to note treatments received and their perceptions of the helpfulness of these treatments. Data from the 77‐item questionnaire were subjected to a principal components analysis. Results: The reasons rated as most important causes of depression related to recent bereavement, imbalance in brain chemistry and having suffered sexual assault/abuse. The data were best described by a two‐factor solution, with the first factor clearly representing stress and the second factor depressogenic beliefs, the latter corresponding to a cognitive–behavioural formulation of depression aetiology. The two scales thus derived did not, however, correspond substantially with rated helpfulness for different treatments received. Conclusions: The factor structure obtained was in contrast to more complex models from previous studies, comprising two factors. It is likely to be more robust and meaningful. It accords with previous research on lay theories of depression, which highlight ‘stress’ as a key cause for depression. Possible limitations in the study are discussed, and it is suggested that using the questionnaire with more recently depressed people might yield clearer findings in relation to perceptions of treatment helpfulness. Copyright © 2008 John Wiley & Sons, Ltd.
Developmental impairments of select neurotransmitter systems in brains of Cln3Δex7/8 knock‐in mice, an animal model of juvenile neuronal ceroid lipofuscinosis
Authors: Herrmann Philipp , Druckrey‐Fiskaaen Caroline , Kouznetsova Elena , Heinitz Katrin , Bigl Marina , Cotman Susan L. , Schliebs Reinhard 
Published: February 2008

AbstractThe neuronal ceroidlipofuscinoses (NCL) are a group of neurodegenerative disorders and are the most common lysosomal storage diseases of infancy and childhood. Juvenile NCL is caused by CLN3 mutation, producing retinal degeneration, uncontrollable seizures, cognitive and motor decline, and early death before the age of 30 years. To study the pathogenetic mechanisms of the disease, Cln3 knock‐in mice (Cln3Δex7/8) have been generated, which reproduce the 1.02‐kb deletion in the CLN3 gene observed in more than 85% of juvenile NCL patients. To characterize the impact of the common Cln3 mutation on development of autofluorescent storage material, gliosis, glucose metabolism, oxidative stress, and transmitter receptors during postnatal brain maturation, brain tissue of Cln3Δex7/8 mice at the ages of 3, 4, 5, 6, 9, and 19 months was subjected to immunocytochemistry to label gliotic markers and nitric oxide synthases; photometric assays to assess enzyme activities of glycolysis and antioxidative defense systems; and level of reactive nitrogen species as well as quantitative receptor autoradiography to detect select cholinergic, glutamatergic, and GABAergic receptor subtypes. The developmental increase in cerebral cortical autofluorescent lipofuscin‐like deposition is accompanied by a significant astro‐ and microgliosis, increased activities of lactate dehydrogenase and phosphofructokinase, decreased level of glutathione peroxidase, enhanced amount of reactive nitrogen species, and lowered binding levels of N‐methyl‐D‐aspartate‐ and M1‐muscarinic acetylcholine receptors in select brain regions but hardly in GABAA receptor sites compared with wild‐type mice. Detailed elucidation of the sequence of pathological events during postnatal development highlights new potential strategies for symptomatic treatment of the disease. © 2008 Wiley‐Liss, Inc.
Bioaffinity magnetic reactor for peptide digestion followed by analysis using bottom‐up shotgun proteomics strategy
Authors: Korecká Lucie , Jankovicová Barbora , Krenková Jana , Hernychová Lenka , Slováková Marcela , Le‐Nell Anne , Chmelík Josef , Foret Frantisek , Viovy Jean‐Louis , Bílková Zuzana 
Published: February 2008

AbstractWe report an efficient and streamlined way to improve the analysis and identification of peptides and proteins in complex mixtures of soluble proteins, cell lysates, etc. By using the shotgun proteomics methodology combined with bioaffinity purification we can remove or minimize the interference contamination of a complex tryptic digest and so avoid the time‐consuming separation steps before the final MS analysis. We have proved that by means of enzymatic fragmentation (endoproteinases with Arg‐C or/and Lys‐C specificity) connected with the isolation of specific peptides we can obtain a simplified peptide mixture for easier identification of the entire protein. A new bioaffinity sorbent was developed for this purpose. Anhydrotrypsin (AHT), an inactive form of trypsin with an affinity for peptides with arginine (Arg) or lysine (Lys) at the C‐terminus, was immobilized onto micro/nanoparticles with superparamagnetic properties (silica magnetite particles (SiMAG)–Carboxyl, Chemicell, Germany). This AHT carrier with a determined binding capacity (26.8 nmol/mg of carrier) was tested with a model peptide, human neurotensin, and the resulting MS spectra confirmed the validity of this approach.
Comparison of micelles formed by amphiphilic star block copolymers prepared in the presence of a nonmetallic monomer activator
Authors: Hyun Hoon , Cho Jae Song , Kim Byung Soo , Lee Jung Won , Kim Moon Suk , Khang Gilson , Park Kinam , Lee Hai Bang 
Published: February 2008

AbstractIn this article, we describe the synthesis of PEG‐b‐polyester star block copolymers via ring‐opening polymerization (ROP) of ester monomers initiated at the hydroxyl end group of the core poly(ethylene glycol) (PEG) using HCl Et2O as a monomer activator. The ROP of ε‐caprolactone (CL), trimethylene carbonate (TMC), or 1,4‐dioxan‐2‐one (DO) was performed to synthesize PEG‐b‐polyester star block copolymers with one, two, four, and eight arms. The PEG‐b‐polyester star block copolymers were obtained in quantitative yield, had molecular weights close to the theoretical values calculated from the molar ratio of ester monomers to PEG, and exhibited monomodal GPC curves. The crystallinity of the PEG‐b‐polyester star block copolymers was determined by differential scanning calorimetry and X‐ray diffraction. Copolymers with a higher arm number had a higher tendency toward crystallization. The crystallinity of the PEG‐b‐polyester star block copolymers also depended on the nature of the polyester block. The CMCs of the PEG‐b‐PCL star block copolymers, determined from fluorescence measurements, increased with increasing arm number. The CMCs of the four‐arm star block copolymers with different polyester segments increased in the order 4a‐PEG‐b‐PCL < 4a‐PEG‐b‐PDO < 4a‐PEG‐b‐PLGA < 4a‐PEG‐b‐PTMC, suggesting a relationship between CMC and star block copolymer crystallinity. The partition equilibrium constant, Kv, which is an indicator of the hydrophobicity of the micelles of the PEG‐polyester star block copolymers in aqueous media, increased with decreasing arm number and increasing crystallinity. A key aspect of the present work is that we successfully prepared PEG‐b‐polyester star block copolymers by a metal‐free method. Thus, unlike copolymers synthesized by ROP using a metal as the monomer activator, our copolymers do not contain traces of metals and hence are more suitable for biomedical applications. Moreover, we confirmed that the PEG‐b‐polyester star block copolymers form micelles and hence may be potential hydrophobic drug delivery vehicles. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2084–2096, 2008
On modeling the effects of T‐cell vaccines on HIV acquisition and disease
Authors: Wick W. David 
Published: February 2008

AbstractA ‘T‐cell vaccine’ aims at generating cytotoxic T‐lymphocytes (CTLs; the so‐called ‘killer’ T‐cells) rather than antibodies (as for traditional vaccines). The first (phase IIb) trials of this concept against HIV/AIDS began in 2004. What can mechanistic modeling contribute to understanding the biological action of this class of vaccines, if any? Models are appropriate in any discussion of three potential vaccine effects: on acquisition of infection; on state of disease (‘viral load’, VL) after infection; and on preventing escape from immune control. Concerning the first two, P. Gilbert, S. Self and I introduced new stochastic models of early HIV infection and the CTL response, and, making use of recent estimates (derived in collaboration with O. Yang and L. Corey) of the rate that CTLs can kill HIV‐infected cells, made the (surprising?) discovery that CTLs might prevent some infections—as the trial designers implicitly acknowledged when they chose the dual end points of the study. On sustaining control, we have derived a theoretical formula for the rate of escape by stepwise mutation and a new method of simulating HIV and CTL dynamics in vivo (permitting new mutant strains a stochastic evolution—essential, in our view). These quantitative models and simulation techniques can also prove useful to biostatisticians. For example, in preparation for the STEP trials, Gilbert, Bosch, and Hudgens developed a novel technique for estimating a causal effect of a vaccine on VL while accounting for post‐randomization selection bias. By simulating thousands of trials, we demonstrated that GBH's method can correctly identify efficacy while protecting against falsely concluding that the vaccine exacerbates disease. When trial data becomes available, the models may also be exploited to make complementary analyses which, while not relevant to vaccine licensure, may suggest new biological hypotheses. Copyright © 2008 John Wiley & Sons, Ltd.
The mentor–youth alliance: The role of mentoring relationships in promoting youth competence
Authors: Zand Debra H. , Thomson Nicole , Cervantes Richard , Espiritu Rachele , Klagholz Donna , LaBlanc Laura , Taylor Andrea 
Published: February 2008

AbstractMentoring programs hold great promise for fostering competency in disadvantaged youth. Although considerable theoretical work has been conducted to explain the role of mentoring relationships in promoting positive youth outcomes, very little empirical research has directly investigated this alliance. The present study developed and validated a tool to assess mentees’ perceptions of their relationships with their mentors and to investigate the relationship between this alliance and youth competency. Based on pilot data from four cross‐national mentoring programs (N=276), a 10‐item, two‐factor Mentor–Youth Alliance Scale (MYAS) was created. Subsequent confirmatory factor analyses conducted on national evaluation data from a multi‐site study of mentoring programs (N=219), generated a 10‐item, one‐factor solution. The one‐factor MYAS significantly predicted youths’ scores in four competency domains: Family Bonding, Relationships with Adults, School Bonding, and Life Skills, at 8‐months post‐intake. Higher competency youth were more likely to be female, younger on average, and have a higher quality of relationships with their mentors than were lower competency youth. Implications for the development of the mentor–protégé relationship are discussed.
Depressed Mood Over Time after Open Heart Surgery Impacts Patient Well-Being: A Combined Study
Authors: Karlsson Ann-Kristin , Lidell Evy , Johansson Mats 
Published: February 2008

Background: Depression is a common cause of decreased well-being after open heart surgery (OHS) and a risk factor for new cardiac events. Little is known about the long-term prevalence of depressive symptoms after OHS or their effect on well-being. The aim of this study was to explore the presence of depressed mood in patients during the recovery phase after open heart surgery as well as depressed mood and well-being 3 years later. Method: Eighty consecutively included patients completed a questionnaire about depressed mood at 5 weeks, 5 months and 3 years after OHS. A telephone interview took place after receipt of the third questionnaire to explore their well-being. Quantitative and qualitative data were analysed separately and thereafter together. Result: Depressed mood occurred in 52% of the patients during recovery or 3 years after OHS. The qualitative content analysis produced the theme of transition, which was based on three categories. Conclusion: Depressed mood was reported by the majority of patients during recovery after OHS and had a long-term effect on their well-being. OHS constituted a transition for all patients, but those with depressed mood had difficulty finishing the transition process and reorientating life.
Evidence that 3‐hydroxyisobutyric acid inhibits key enzymes of energy metabolism in cerebral cortex of young rats
Authors: Viegas Carolina Maso , da Costa Ferreira Gustavo , Schuck Patrícia Fernanda , Tonin Anelise Miotti , Zanatta Ângela , de Souza Wyse Angela Terezinha , Dutra‐Filho Carlos Severo , Wannmacher Clóvis Milton Duval , Wajner Moacir 
Published: February 2008

Abstract3‐Hydroxyisobutyric aciduria is an inherited metabolic disease caused by 3‐hydroxyisobutyryl‐CoA dehydrogenase deficiency. Tissue accumulation and high urinary excretion of 3‐hydroxyisobutyric acid is the biochemical hallmark of this disorder. Clinical phenotype is heterogeneous and generally includes dysmorphic features, delayed motor development, profound mental impairment, and acute encephalopathy. Lactic acidemia is also found in the affected patients, indicating that mitochondrial dysfunction may be involved in the pathophysiology of this disorder. Therefore, the aim of the present work was to investigate the in vitro effect of 3‐hydroxyisobutyric acid (0.1, 0.5 and 1 mM) on essential enzymes of energy metabolism, namely the activities of the respiratory chain complexes I–V, total, cytosolic and mitochondrial creatine kinase and Na+, K+‐ATPase in cerebral cortex homogenates of 30‐day‐old rats. We also measured the rate of oxygen consumption in brain mitochondrial preparations in the presence of 3‐hydroxyisobutyric acid. 3‐Hydroxyisobutyric acid significantly reduced complex I–III (20%), without affecting the other activities of the electron transport chain. Furthermore, 3‐hydroxyisobutyric acid did not change state III, state IV and the respiratory control ratio in the presence of glutamate/malate or succinate, suggesting that its effect on cellular respiration was weak. On the other hand, the activities of total and mitochondrial creatine kinase, but not cytosolic creatine kinase, were inhibited (30%) by 3‐hydroxyisobutyric acid. We also observed that 3‐hydroxyisobutyric acid‐induced inhibition of mitochondrial creatine kinase activity was fully prevented by pre‐incubation of the homogenates with reduced glutathione, α‐tocopherol or the combination of superoxide dismutase plus catalase, suggesting that this inhibition was mediated by oxidation of essential thiol groups of the enzyme probably by superoxide, hydrogen peroxide and/or peroxyl radicals. It was also demonstrated that Na+, K+‐ATPase activity from synaptic plasma membranes was markedly suppressed (37%) by 3‐hydroxyisobutyric acid and that this effect was prevented by α‐tocopherol co‐incubation implying that peroxyl radicals were probably involved in this action. Considering the importance of the affected enzyme activities for brain metabolism homeostasis and neurotransmision, it is suggested that increased tissue levels of 3‐hydroxyisobutyric acid may contribute to the neurodegeneration of patients affected by 3‐hydroxyisobutyric aciduria and possibly explain previous reports describing elevated production and excretion of lactate.
Melatonin inhibitory effect on cAMP accumulation in the chick retina development
Authors: Sampaio Lucia de Fatima Sobral 
Published: February 2008

AbstractDuring vertebrate neurodevelopment, neuritogenesis and synaptogenesis are modulated by intracellular cAMP rises. Melatonin, which is implicated in neuronal differentiation, mainly inhibits this pathway. Here, an investigation about the profile of this effect during the vertebrate neurodevelopment is reported. In the embryonic chick retinas at days 8, 12, 14, 16 and at 2 days post‐hatched (E8, E12, E14, E16 and PH), those control embryonic retinas incubated only with the phosphodiesterase inhibitor at days corresponding to commencement of neuronal differentiation (E8, E12) and PH, presented cAMP levels inhibited by melatonin. While the cAMP accumulation stimulated by forskolin was inhibited in the embryonic retinas at all testing days. Neither the unselective antagonist N‐acetyl‐2‐benziltryptamine (luzindole) nor the selective Mel1b antagonist 4‐phenyl‐2‐propionamidotetralin (4‐P‐PDOT) blocked the melatonin concentration‐dependent inhibitory effect on cAMP accumulation in the retinas initiating differentiation (E7 − E9), suggesting a tight binding between melatonin and their receptors. However, 4‐P‐PDOT competitively reverted the melatonin effect on cAMP stimulated by forskolin during synaptogenesis stages. Together, the melatonin effect on cAMP levels in chick retina, which is mainly through melatonin receptors, is depending on the developmental period observed, probably taking part in the mechanisms surrounding the melatonin action on neuronal differentiation.
Stereotypes, stereotype threat and ageing: implications for the understanding and treatment of people with Alzheimer's disease
Authors: SCHOLL JANE M. , SABAT STEVEN R. 
Published: February 2008

ABSTRACTOver the past 15 years, a growing body of research has shown that people with Alzheimer's disease (AD) are affected not only by brain neuropathology but also by their reactions to its effects, by the environments in which they live, and by how they are treated by others. Nevertheless, three relatively neglected social influences on people with AD remain to be examined: negative stereotyping, negative self-stereotyping and stereotype threat. Numerous studies reviewed in this paper indicate that: (1) negative self-stereotypes at conscious and unconscious levels can have adverse effects on the performance of healthy elderly people on tasks demanding explicit memory (recall in particular), and (2) the mere threat of being stereotyped negatively can have adverse effects on the performance of healthy elderly people on tasks including those involving memory. In this paper, we discuss the relevance of these phenomena for our understanding and treatment of people with AD who are exposed to negative stereotypes about old age and about AD before and after they are diagnosed. There is evidence to suggest that these influences may have significant effects on people with AD. The paper concludes with recommendations for best practice in the treatment of people with AD in the light of the most apparent effects of negative self-stereotyping and stereotype threat. These include advocacy for an approach that involves aspects of counselling.
The new water‐soluble artemisinin derivative SM905 ameliorates collagen‐induced arthritis by suppression of inflammatory and Th17 responses
Authors: Wang J‐X , Tang W , Zhou R , Wan J , Shi L‐P , Zhang Y , Yang Y‐F , Li Y , Zuo J‐P 
Published: February 2008

Background and purpose:Our previous study showed that SM905, a novel artemisinin derivative, exhibited potent immunosuppressive activity. In this study, we evaluate preventive and therapeutic effect of SM905 on collagen‐induced arthritis (CIA) in DBA/1 mice, and investigate its mechanisms both in inflammatory and autoimmune aspects of the disease.Experimental approach:CIA was induced by type II bovine collagen (CII) in DBA/1 mice. SM905 was given orally either before (continuously 1 day before booster immunization) or after disease onset (continuously 14 days after booster immunization). Disease incidence and severity were monitored, mRNA expression of proinflammatory mediators was determined by real‐time PCR, purified T cell proliferation was assessed using [3H]‐thymidine incorporated assay, and T helper (Th) 17/Th1/Th2 type cytokine production was examined by ELISA.Key results:Oral treatment with SM905 delayed disease onset, reduced arthritis incidence and severity, and suppressed the enhanced expression of pro‐inflammatory cytokines, chemokines and chemokine receptors in draining lymph nodes. The CII‐induced T cell proliferation and production of interleukin (IL)‐17A by T cells were strikingly inhibited. Correspondingly, the mRNA expression of IL‐17A and RORγt (a specific transcription factor for Th17) was also reduced. This effect was coupled with a striking reduction of IL‐6 production, which has a critical role in Th17 development. In established arthritis, SM905 profoundly inhibited disease progression, reduced IL‐17A and RORγt mRNA expression, and suppressed pro‐inflammatory mediator expression in arthritic joints.Conclusions and implications:SM905 had beneficial effects on CIA by suppressing inflammatory and pathogenic Th17 responses.British Journal of Pharmacology (2008) 153, 1303–1310; doi:10.1038/bjp.2008.11; published online 11 February 2008
Secretory PLA2 inhibitor indoxam suppresses LDL modification and associated inflammatory responses in TNFα‐stimulated human endothelial cells
Authors: Sonoki K , Iwase M , Sasaki N , Ohdo S , Higuchi S , Takata Y , Iida M 
Published: February 2008

Background and purpose:Secretory phospholipase A2 (sPLA2) is implicated in atherosclerosis, although the effects of specific sPLA2 inhibitors have not been studied. We investigated the effects of the indole analogue indoxam on low‐density lipoprotein (LDL) modification by sPLA2 enzymes of different types and on the associated inflammatory responses in human umbilical vein endothelial cells (HUVEC).Experimental approach:LDL modification was assessed by measuring the contents of two major molecular species of lysophosphatidylcholine (LPC) using electrospray ionization‐liquid chromatography/mass spectrometry. The proinflammatory activity of the modified LDL was evaluated by determining monocyte chemoattractant protein‐1 (MCP‐1) mRNA expression and transcriptional factor nuclear factor‐kappaB (NF‐κB) activity in HUVEC.Key results:Indoxam dose‐dependently inhibited palmitoyl‐ and stearoyl‐LPC production in LDL incubated with snake venom sPLA2 (IC50 1.2 μM for palmitoyl‐LPC, 0.8 μM for stearoyl‐LPC). MCP‐1 mRNA expression and NF‐κB activity were enhanced by venom sPLA2‐treated LDL, which was completely suppressed by indoxam but not by thioetheramide‐PC, a competitive sPLA2 inhibitor. Indoxam also suppressed LPC production in LDL treated with human synovial type IIA sPLA2. Tumour necrosis factor α (TNFα) increased type V sPLA2 expression in HUVEC. Indoxam dose‐dependently suppressed LPC production in native and glycoxidized LDL treated with TNFα‐stimulated HUVEC. Indoxam suppressed MCP‐1 mRNA expression and NF‐κB activity in TNFα‐stimulated HUVEC incubated with native or glycoxidized LDL.Conclusions and implications:Indoxam prevented sPLA2‐induced LPC production in native and glycoxidized LDL as well as LDL‐induced inflammatory activity in HUVEC. Our results suggest that indoxam may be a potentially useful anti‐atherogenic agent.British Journal of Pharmacology (2008) 153, 1399–1408; doi:10.1038/bjp.2008.12; published online 11 February 2008