bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative metabolism of benzo(a)pyrene by ovarian microsomes of various species
Authors: Harris Deacqunita L. , Huderson Ashley C. , Niaz Mohammad S. , Ford J. Joe , Archibong Anthony E. , Ramesh Aramandla
Published: December 2008

Knowledge of the ability of the female reproductive system to metabolize polycyclic aromatic hydrocarbons (PAHs) is critical to the diagnosis and management of female infertility and for risk assessment purposes. The PAHs are a family of widespread pollutants that are released into the environment from automobile exhausts, cigarette smoke, burning of refuse, industrial emissions, and hazardous waste sites. In exposed animals, PAHs become activated to reactive metabolites that interfere with target organ function and as a consequence cause toxicity. The extent of susceptibility to PAH exposure may depend on the ability of animals to metabolize these chemicals. The present study has been undertaken to assess whether any differences exist among mammals in the metabolism of benzo(a)pyrene (BaP), a prototypical PAH compound. Microsomes isolated from the liver and ovaries of rats, mice, goats, sheep, pigs, and cows were incubated with 5 μM BaP. Postincubation, samples were extracted with ethyl acetate and analyzed for BaP/metabolites by reverse‐phase HPLC with fluorescence detection. The rate of metabolism (pmol of metabolite/min/mg protein) was found to be more in liver than in ovary in all the species studied (P< 0.05). The differences in metabolite concentrations were statistically significant (P< 0.0001) among the various species in both organs studied. Multiple species comparison also revealed that the differences were statistically significant (P< 0.001) between rodents (rat and mouse) and higher mammals (ewe, sow, and cow). Even among the higher mammals, in a majority of the cases, the differences in metabolite concentrations were significantly different (P< 0.001) both in ovary and liver. The BaP metabolites identified were 4,5‐diol; 7,8‐diol; 9,10‐diol; 3‐hydroxy BaP; and 9‐hydroxy BaP. The rodent microsomes produced considerably higher proportion of BaP 4,5‐diol and 9,10‐diol than did cow, sow, goat, and sheep. However, microsomes from higher mammals converted a greater proportion of BaP to 3‐hydroxy and 9‐hydroxy BaP, the detoxification products of BaP. Overall, our results revealed a great variation among species to metabolize BaP. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2009.
Direct Interband Light Absorption in Strongly Prolated Ellipsoidal Quantum Dots’ Ensemble
Authors: Dvoyan KG , Hayrapetyan DB , Kazaryan EM
Published: December 2008

Within the framework of adiabatic approximation, the energy levels and direct interband light absorption in a strongly prolated ellipsoidal quantum dot are studied. Analytical expressions for the particle energy spectrum and absorption threshold frequencies in three regimes of quantization are obtained. Selection rules for quantum transitions are revealed. Absorption edge and absorption coefficient for three regimes of size quantization (SQ) are also considered. To facilitate the comparison of obtained results with the probable experimental data, size dispersion distribution of growing quantum dots by the small semiaxe in the regimes of strong and weak SQ by two experimentally realizing distribution functions have been taken into account. Distribution functions of Lifshits–Slezov and Gaussian have been considered.
Classification of Four Almond Cultivars Using Oil Degradation Parameters Based on FTIR and GC Data
Authors: Beltrán Sanahuja A. , Prats Moya M. S. , Maestre Pérez S. E. , Grané Teruel N. , Martín Carratalá M. L.
Published: December 2008

Four almond cultivars (Marcona, Guara, Garrigues and Butte) have been classified using attenuated total reflectance Fourier transform infrared spectroscopy (ATR‐FTIR) and gas chromatography (GC) data. The data were obtained by completing the first stages of a thermal oxidative degradation process. The degradation process was monitored by using the variations in the main fatty acid methyl esters (FAME) content determined by GC and to changes in the infrared spectra recorded using the ATR‐FTIR technique. In order to classify the almond cultivars, a stepwise linear discriminant analysis was applied to the data. The results indicated that, although the four almond oils evaluated here have a similar fatty acid composition, differences in linoleic acid content may be linked to oxidative stability. Butte cultivar samples had higher linoleic acid content and were more prone to oxidative deterioration.
Multiplex fluorimetric assays for monitoring algal toxins
Authors: Mak Carmen K.M. , Yeung Patrick K.K. , Kwok Alvin C.M. , Wong Y.H. , Wong Joseph T.Y.
Published: December 2008

Most known algal toxins act on ion channels either directly or indirectly, resulting in a change in intracellular ion concentrations when administered to targeted cells. The present project developed the working conditions for the use of fluorescent dyes in monitoring changes in membrane potential, intracellular calcium, and intracellular sodium levels in mammalian cell lines. Using these conditions, we were able to demonstrate specific changes in fluorescent signals in response to several purified toxins. We were also able to generate algal extracts which, when administered to the developed fluorimetric assays, were able to elicit different pattern of changes in membrane potential, intracellular calcium, and intracellular sodium levels. The differential pattern of responses induced by the different algal toxins in the three fluorimetric assays serve as a proof of concept for the use of multiplex fluorimetric assays in the laboratory monitoring of algal toxins.
Obsessive–compulsive disorder: subclassification based on co-morbidity
Authors: Nestadt G. , Di C. Z. , Riddle M. A. , Grados M. A. , Greenberg B. D. , Fyer A. J. , McCracken J. T. , Rauch S. L. , Murphy D. L. , Rasmussen S. A. , Cullen B. , Pinto A. , Knowles J. A. , Piacentini J. , Pauls D. L. , Bienvenu O. J. , Wang Y. , Liang K. Y. , Samuels J. F. , Roche K. Bandeen
Published: December 2008

Background

Obsessive–compulsive disorder (OCD) is probably an etiologically heterogeneous condition. Many patients manifest other psychiatric syndromes. This study investigated the relationship between OCD and co-morbid conditions to identify subtypes.

Method

Seven hundred and six individuals with OCD were assessed in the OCD Collaborative Genetics Study (OCGS). Multi-level latent class analysis was conducted based on the presence of eight co-morbid psychiatric conditions [generalized anxiety disorder (GAD), major depression, panic disorder (PD), separation anxiety disorder (SAD), tics, mania, somatization disorders (Som) and grooming disorders (GrD)]. The relationship of the derived classes to specific clinical characteristics was investigated.

Results

Two and three classes of OCD syndromes emerge from the analyses. The two-class solution describes lesser and greater co-morbidity classes and the more descriptive three-class solution is characterized by: (1) an OCD simplex class, in which major depressive disorder (MDD) is the most frequent additional disorder; (2) an OCD co-morbid tic-related class, in which tics are prominent and affective syndromes are considerably rarer; and (3) an OCD co-morbid affective-related class in which PD and affective syndromes are highly represented. The OCD co-morbid tic-related class is predominantly male and characterized by high conscientiousness. The OCD co-morbid affective-related class is predominantly female, has a young age at onset, obsessive–compulsive personality disorder (OCPD) features, high scores on the ‘taboo’ factor of OCD symptoms, and low conscientiousness.

Conclusions

OCD can be classified into three classes based on co-morbidity. Membership within a class is differentially associated with other clinical characteristics. These classes, if replicated, should have important implications for research and clinical endeavors.
Integrating Welfare and Production Typologies: How Refinements of the Varieties of Capitalism Approach call for a Combination of Welfare Typologies
Authors: SCHRÖDER MARTIN
Published: December 2008

This article argues that existing typologies on production and welfare regimes should be combined into a typology unifying the study of production and distribution in advanced capitalist countries. The article utilises a principal component and cluster analysis to show that such a typology indeed reflects the empirical diversity of countries. This is further illustrated by a brief literature review of different typologies. It is then shown how the integration of the two approaches helps to resolve problems addressed in the new literature on the varieties of capitalism approach, notably how welfare arrangements relate to production systems. Thereby, the relevance of an integrated typology for policy-makers in the fields of welfare and production will be illustrated. Lastly, some thoughts follow on how an integrated typology allows for a perspective that explains the development of various welfare and production regimes based on the common historical heritage of families of nations.
What Welfare States Do: A Disaggregated Expenditure Approach
Authors: CASTLES FRANCIS G.
Published: December 2008

This article suggests that an alternative to a social rights of citizenship approach to comparing welfare states is to use disaggregated programme expenditure data to identify the diverse spending priorities of different types of welfare state. An initial descriptive analysis shows that four major categories of social spending (cash spending on older people and those of working age; service spending on health and for other purposes) are almost entirely unrelated to one another and that different welfare state regimes or families of nations exhibit quite different patterns of spending. The article proceeds to demonstrate that both the determinants and the outcomes of these different categories of spending also differ quite radically. In policy terms, most importantly, the article shows that cross-national differences in poverty and inequality among advanced nations are to a very large degree a function of the extent of cash spending on programmes catering to the welfare needs of those of working age.
The Evolution of Choice Policies in UK Housing, Education and Health Policy
Authors: GREENER IAN , POWELL MARTIN
Published: December 2008

Scholarship in social policy in recent years has examined how policy positions users in a range of roles, particularly most recently in terms of their roles as ‘choosers’ through the increased use of markets in welfare. This article considers how choice policies have positioned users since the creation of the modern welfare state, presenting a history of choice policies, but also a comparative examination of how they have differed in the UK between housing, education and healthcare. It concludes by suggesting that although approaches to choice vary considerably between the three public services examined, policy-makers often appear unaware of these differences, leading to mistaken assumptions that policies can be transferred or transplanted unproblematically.
Relationships of Care: Working Lone Mothers, their Children and Employment Sustainability
Authors: MILLAR JANE , RIDGE TESS
Published: December 2008

Lone mothers are a key target group for government policies to increase employment participation rates. Employment sustainability is central to achieving this goal and thus it is important to understand the factors that affect sustainability. When the lone mother starts work, her daily life changes in various ways, and so do the lives of her children, and perhaps also other family members who may become involved in childcare, or in other forms of help. These social relationships – at home, in work, in care settings, at school – may be a key element in employment sustainability, and one that has not yet been systematically explored in research. This article draws on data from an ongoing longitudinal qualitative study of lone mothers and their children, which has been following the families from the point that the mothers left income support and started working for at least 16 hours per week. The analysis starts from the assumption that sustaining work over time is a process that actively involves the family as a whole and not just the individual lone mother. In this article we explore how social relationships, inside and outside the family, are central to the ‘family–work project’ of sustaining employment.
Acute gastroenteritis caused by multiple enteric pathogens in children
Authors: CHEN S.-Y. , TSAI C.-N. , CHAO H.-C. , LAI M.-W. , LIN T.-Y. , KO T.-Y. , CHIU C.-H.
Published: December 2008

Of 303 children hospitalized with acute non-bloody, non-mucoid diarrhoea, 69 (22·8%) had polymicrobial infection, including 52 (17·2%) multiple viral infection and 17 (5·6%) viral and bacterial co-infection. Rotavirus had the most important role in both categories; thus the control of rotavirus infection is crucial for maintaining children's health in Taiwan.
Short Note: Second Jurassic marine reptile from the Antarctic Peninsula
Authors: Hikuroa Daniel C.H.
Published: December 2008

Except for the rich record from the Neuquen Basin (e.g. Gasparini & Fernández 2006), Jurassic southern Gondwanan marine reptiles are relatively rare. A tooth discovered in the Bean Peaks, Ellsworth Land, Antarctic Peninsula (Fig. 1) represents the southernmost, and only the second record of Jurassic marine reptiles from the Antarctic Peninsula. Comprising a single, incomplete tooth, the specimen is unable to be assigned to a species, but the paucity of Gondwanan Jurassic marine reptile material means this find adds significant palaeobiogeographical information.
Strain variation associated with the development of a major recumbent curvilinear fold in the Dalradian rocks of NW Achill Island, western Ireland
Authors: Harris David H. M. , Harris Anthony L.
Published: December 2008

The regionally metamorphosed, Riphean–Cambrian Argyll Group Dalradian rocks of NW Achill Island, western Ireland are disposed in a large-scale, regionally west-facing, tight, recumbent F2 curvilinear fold, with which two ductile shear zones are associated. Clasts in conglomerates within the Dalradian sequence that are deformed by the shear zones preserve evidence for a constrictional overprint of earlier plane strain as the fold became curvilinear, while stretched clasts maintained a constant orientation as the hinge curvilinearity developed. During the constrictional overprint a crenulation fabric, S2b, overprinted a penetrative foliation, S2a, in the shear zones. The S2b has an orientation that varies systematically with that of the fold hinge. It is inferred that, although the S2b surfaces initiated as a dip-slip fabric, there was an increasing degree of strike slip on these surfaces as the fold hinge approached parallelism with the direction of tectonic transport. It is possible that many curvilinear folds have an early history involving plane strain, but that increasing constrictional strain is intrinsic to the later stages of their development.
Es ist schwieriger, eine vorgefasste Meinung zu zertrümmern als ein Atom
Authors: Krapf Reto
Published: December 2008

Der Hinschied einer 17-jährigen Patientin an einer Hypokaliämie-bedingten Herzrhythmusstörung bringt die tragischen Gefahren des Schönheits- und Schlankheitswahns bei jungen Frauen zum Bewusstsein. Der Fall illustriert auch, dass Lehrbuchwissen nicht immer verlässlich ist. Mit welchem intellektuell-rationalen Vorgehen könnte man trotzdem Fehlbeurteilungen verhindern?
Eine sinn- und bewusstlose Odyssee
Authors: Reinhart Walter H.
Published: December 2008

Ein 76-jähriger ehemaliger Reeder mit einer vorbestehenden unklaren Pneumopathie erlitt im Anschluss an eine Operation wegen Schenkelhalsfraktur in Deutschland eine massive Lungenembolie mit Kreislaufinstabilität und respiratorischer Insuffizienz, die eine Intubation nötig machte. In diesem Zustand trat der Patient eine beispiellose Odyssee an, weil die Ehefrau aus Unzufriedenheit über seinen Zustand und die ärztliche Behandlung immer weitere Verlegungen erzwang. Zuerst musste er ins Spital Oberengadin geflogen werden, wo er wochenlang mit mehreren Rückschlägen vom Respirator entwöhnt und tracheotomiert wurde. Dann folgte die Verlegung ins Spital Unterengadin, wo ein großer Perikarderguss drainiert wurde und der Patient wegen akuter respiratorischer Verschlechterung ins Kantonsspital in Chur geflogen werden musste. Dann wurde er auf Drängen der Gattin gegen jeden ärztlichen Rat nach Hause zurückgeflogen, wo er wenige Stunden nach Ankunft verstarb und sich die Ehefrau anschließend das Leben nahm. Warum konnte niemand diese sinnlose Irrfahrt stoppen?
Häufiges war häufig und Seltenes wird häufiger – Tuberkulose, die alte Bekannte
Authors: Tresselt Christiane , Hösli Irene
Published: December 2008

Während einer Schwangerschaft kann eine neu diagnostizierte Tuberkulose zahlreiche Probleme und Fragen aufwerfen. Im Folgenden wird die Krankengeschichte einer 24-jährigen portugiesischen Patientin mit unklarem Gewichtsverlust und unspezifischen Symptomen wie Müdigkeit und Übelkeit in der Schwangerschaft vorgestellt. Die Patientin wurde engmaschig kontrolliert und auf Grund ihrer sozialen Belastungssituation psychosomatisch betreut. Erst gegen Ende der Schwangerschaft konnte eine Tuberkulose (Tbc) diagnostiziert und die Patientin adäquat therapiert werden. Es wird die Therapie in der Schwangerschaft erläutert und die Frage des Stillens diskutiert.
Kalebassen und andere Geschichten
Authors: Huynh-Do Uyen
Published: December 2008

Bei den Urvölkern symbolisiert die doppelbauchige Kalebasse das Universum, zwei gleichwertige Hälften, die untrennbar miteinander verbunden sind. Sie repräsentieren Himmel und Erde, Yin und Yang – die Ausgewogenheit und Harmonie. Der Beitrag beschreibt persönliche Erinnerungsstücke, die jeweils mit Krankengeschichten, Patientengeschichten und einer Arztgeschichte verwoben sind.
Forschungsprioritäten und Forschungsthemen im Bereich der kardiovaskulären Pflege: Die schweizerische Agenda für die Pflege
Authors: Mahrer-Imhof Romy , Imhof Lorenz
Published: December 2008

Kardiovaskuläre Erkrankungen sind eine große Herausforderung für das Gesundheitswesen weltweit. Auch in der Schweiz sind diese Erkrankungen Grund Nummer eins für Mortalität und verlorene Lebensjahre. Viele Anstrengungen zur Bekämpfung der Risikofaktoren, zur Verbesserung der Behandlungen in akuten und chronischen Phasen und Rehabilitation von Betroffenen sind von der medizinischen Forschung ausgegangen. Auch pflegewissenschaftliche Forschung hat einen wesentlichen Beitrag geleistet um die Veränderung von Risikoverhalten und die Anpassung an Krankheit und Therapie von Patienten zu verstehen und zu unterstützen. Im Bereich der kardiovaskulären Pflege besteht in den USA eine lange Tradition. Auch in Europa entwickelte sich die kardiovaskuläre Pflegeforschung in der letzten Dekade, an der sich auch zunehmend Pflegeforschende aus der Schweiz beteiligen. Ziel ist es, Grundlagen für evidenzbasierte Pflegeinterventionen zu entwickeln, welche die Gesundheit der Bevölkerung und das Wohlergehen der Menschen mit Herz-Kreislauferkrankungen bei akuten und chronischen Verläufen fördern. Da eine literaturbasierte und expertengestützte Agenda für die Pflegeforschung im deutsch- und französischsprachigen Schweizer Raum fehlte, war es Ziel des Swiss Research Agenda for Nursing (SRAN) Projekts, eine Agenda zur Orientierung der Forschenden, der Geldgeber und der politischen Gremien zu entwickeln. Die vorliegende Arbeit nimmt die sieben Schwerpunkte des SRAN-Projekts auf und setzt sie mit den Schwerpunkten Veränderung von Risikofaktoren, Rehabilitationsprogramme, Selbstpflegeverhalten und Schulung und Beratung in der kardiovaskulären Pflege in Verbindung. Mit der vorliegenden Arbeit wird erstmals eine Schweizerische Agenda für die kardiovaskuläre Pflegeforschung für die Jahre 2007 bis 2017 präsentiert, die als Grundlage zur Entwicklung von Forschungsprogrammen und einzelnen Forschungsprojekten dienen kann.
Forschungsprioritäten für die Pflege in der Psychiatrie
Authors: Abderhalden Christoph , Hahn Sabine , Hantikainen Virpi , Rabenschlag Franziska , Sprenger Rosmarie
Published: December 2008

Verschiedene nationale und internationale Organisationen betonen in neueren gesundheitspolitischen Positionspapieren, dass psychischer Gesundheit und psychischer Krankheit größere Beachtung geschenkt werden muss. Gründe dafür sind einerseits der große Einfluss psychischer Faktoren auf die allgemeine Gesundheit der Bevölkerung, anderseits das enorme Ausmaß von Krankheitslast (burden of disease), die durch psychiatrische Erkrankungen verursacht wird. Die zunehmende Beachtung psychischer Gesundheit und Krankheit ist auch für die Pflege und die Pflegeforschung von großer Relevanz. Im vorliegenden Artikel wird beschrieben, wie als Beitrag der «Swiss Research Agenda for Nursing (SRAN)» Forschungsprioritäten für den Bereich der psychiatrischen Pflege identifiziert und priorisiert wurden. Mittels einer Literaturanalyse zu psychiatrischen und psychiatriepflegerischen Forschungsprioritäten sowie durch Diskussionen an Fachtagungen wurden insgesamt 54 Forschungsthemen identifiziert und anschließend durch ExpertInnen in eine Prioritätenordnung gebracht. Die höchsten Prioritäten wurden der vermehrten Berücksichtigung des ambulanten und außerklinischen Bereichs, der Prävention und Gesundheitsförderung sowie der Fokussierung einer an Public-Health-Aspekten orientierten Interventions- und Versorgungsforschung beigemessen. Die identifizierten Forschungsthemen und -prioritäten werden in Beziehung gesetzt zu den übergeordneten Prioritäten der «Agenda für die klinische Pflegeforschung in der Schweiz». Sie werden die Basis sein für die Formulierung eines Umsetzungsplans dieser Agenda im Bereich der psychiatrischen Pflege.
Kognition und Gedächtnis bei Patienten mit schlafbezogenen Atmungsstörungen
Authors: Reinhold Nadine , Clarenbach Peter , Markowitsch Hans J.
Published: December 2008

Neben Tagesschläfrigkeit sollen Patienten mit schlafbezogenen Atmungsstörungen (SBAS) ohne nCPAP-Therapie (nasal Continuous Positive Airway Pressure) auch kognitive und mnestische Einbussen zeigen, vorrangig in exekutiven Funktionen. Wir vergleichen neuropsychologische Leistungen von 20 Patienten mit leichten und schweren SBAS und betrachten deren Verlauf nach drei Monaten der laufenden nCPAP-Therapie. Hierzu wurden polysomnographische und neuropsychologische Daten von männlichen Patienten mit SBAS vor Beginn und nach dreimonatiger Gerätetherapie erhoben. Auch wenn die erfassten Leistungen vor Therapiebeginn im noch durchschnittlichen Bereich lagen, konnte durch die Ventilationsbehandlung eine Verbesserung der Leistungen insbesondere in exekutiven und mnestischen Funktionen erreicht werden. Es zeigen sich Unterschiede in den verbesserten Bereichen zwischen den leicht und schwer schlafgestörten Patienten. Abschliessend wird dieser Unterschied hinsichtlich störungsspezifischer Parameter diskutiert.
Gibt es eine (Neuro)-Psychologie des Massenmörders?
Authors: Jäncke Lutz
Published: December 2008

Im Rahmen dieses Essays wird diskutiert, ob das Morden oder gar der Massenmord anhand der Kenntnis neuropsychologischer Konzepte erklärt werden kann. Hierbei wird deutlich, dass es quasi jedem Erklärungsversuch für Mord und Massenmord schwer fallen wird, Mord oder Massenmord ohne Zuhilfenahme von konventionellen Regeln zu definieren. Demzufolge bleibt es auch schwierig, wenn nicht gar unmöglich, menschliches Verhalten, dass in Morde oder Massenmorde mündet, mit einfachen und eingängigen neuropsychologischen Modellen zu erklären. Es wird allerdings deutlich, dass das menschliche Gehirn mit einem höchst flexiblen und „lernfähigen“ sozialen Kontrollsystem ausgestattet ist, dass sich an verschiedene soziale Szenarien anpassen kann. Die hohe Anpassungsfähigkeit eröffnet allerdings auch Möglichkeiten für therapeutische und erzieherische Ansätze zur Verhaltensänderung.
Phosphene und Photopsien – Okzipitallappeninfarkt oder Reizdeprivation?
Authors: Engmann Birk
Published: December 2008

Bei einer 85-jährigen Frau stellte sich apoplektiform eine Sehverschlechterung einhergehend mit Phosphenen, Photopsien und pedunkulären Halluzinationen ohne Quadranten- oder Hemianopsie ein. Neben einer ischämischen Genese bei im MRT nachgewiesener subkortikaler vaskulärer Enzephalopathie und kortikalen Läsionen im Bereich der Okzipitallappenpole wird eine ophthalmopathische Halluzinose im Sinne eines Charles- Bonnet- Syndroms bei Reizdeprivation infolge Optikusatrophie und Makuladegeneration diskutiert. Mit der Falldarstellung soll die Bedeutung der Differentialdiagnose halluzinatorischer Phänomene bei älteren Menschen zu psychiatrischen Erkrankungen und dementiellen Syndromen verdeutlicht werden, da sich daraus unterschiedliche medikamentöse Konsequenzen ergeben könnten.
Speeded Paper-Pencil Sustained Attention and Mental Speed Tests
Authors: Krumm Stefan , Schmidt-Atzert Lothar , Michalczyk Kurt , Danthiir Vanessa
Published: December 2008

Mental speed (MS) and sustained attention (SA) are theoretically distinct constructs. However, tests of MS are very similar to SA tests that use time pressure as an impeding condition. The performance in such tasks largely relies on the participants’ speed of task processing (i.e., how quickly and correctly one can perform the simple cognitive tasks). The present study examined whether SA and MS are empirically the same or different constructs. To this end, 24 paper-pencil and computerized tests were administered to 199 students. SA turned out to be highly related to MS task classes: substitution and perceptual speed. Furthermore, SA showed a very close relationship with the paper-pencil MS factor. The correlation between SA and computerized speed was considerably lower but still high. In a higher-order general speed factor model, SA had the highest loading on the higher-order factor; the higher-order factor explained 88% of SA variance. It is argued that SA (as operationalized with tests using time pressure as an impeding condition) and MS cannot be differentiated, at the level of broad constructs. Implications for neuropsychological assessment and future research are discussed.
The Relative Efficacy of Psychotherapy: Reassessing the Methods-Based Paradigm
Authors: Staines Graham L.
Published: December 2008

Because the efficacy of behavioral interventions is central to applied psychology, the relative merits of competing approaches to an intervention are important. Many comparative studies examine the differential outcomes of alternative methods of psychotherapy. This paper addresses the issue of impact differences among rival intervention methods by focusing on treatment outcome research that emphasizes the relative (or comparative) efficacy of different psychotherapies. The paper has 4 components. First, it explores the concept of relative efficacy. Second, it reviews the extensive evidence on relative efficacy, which is generally consistent with the null hypothesis. Third, it offers a 3-part explanation of the negative evidence on relative efficacy: (a) a statistical argument about how relative efficacy is bound by a modest upper limit; (b) a research design argument about how relative efficacy studies are confounded by multiple factors, which make it difficult to demonstrate differences in treatment effects; and (c) a theoretical argument about how therapists’ contributions to treatment outcomes depend more on their clinical abilities than the therapy methods they implement. The final section of the paper outlines questions for future research.
Physarum nitric oxide synthases: genomic structures and enzymology of recombinant proteins
Authors: Messner Simon , Leitner Stephan , Bommassar Christian , Golderer Georg , Gröbner Peter , Werner Ernst R. , Werner-Felmayer Gabriele
Published: December 2008

Physarum polycephalum expresses two closely related, calcium-independent NOSs (nitric oxide synthases). In our previous work, we showed that both NOSs are induced during starvation and apparently play a functional role in sporulation. In the present study, we characterized the genomic structures of both Physarum NOSs, expressed both enzymes recombinantly in bacteria and characterized their biochemical properties. Whereas the overall genomic organization of Physarum NOS genes is comparable with various animal NOSs, none of the exon–intron boundaries are conserved. Recombinant expression of clones with various N-termini identified N-terminal amino acids essential for enzyme activity, but not required for haem binding or dimerization, and suggests the usage of non-AUG start codons for Physarum NOSs. Biochemical characterization of the two Physarum isoenzymes revealed different affinities for L-arginine, FMN and 6R-5,6,7,8-tetrahydro-L-biopterin.
Introduction: Andrew Thomson and the Centre for Metalloprotein Spectroscopy and Biology at the University of East Anglia
Authors: Wilson Michael T.
Published: December 2008

The present article briefly relates the early history and growth of the Centre for Metalloprotein Spectroscopy and Biology at UEA (University of East Anglia) under the joint directorship of A.J. Thomson and C. Greenwood, and charts the exceptional success that this centre has had in fostering bioinorganic chemistry in the U.K. and the impact that it has had internationally.
Iron–sulfur cluster biosynthesis
Authors: Bandyopadhyay Sibali , Chandramouli Kala , Johnson Michael K.
Published: December 2008

Iron–sulfur (Fe–S) clusters are present in more than 200 different types of enzymes or proteins and constitute one of the most ancient, ubiquitous and structurally diverse classes of biological prosthetic groups. Hence the process of Fe–S cluster biosynthesis is essential to almost all forms of life and is remarkably conserved in prokaryotic and eukaryotic organisms. Three distinct types of Fe–S cluster assembly machinery have been established in bacteria, termed the NIF, ISC and SUF systems, and, in each case, the overall mechanism involves cysteine desulfurase-mediated assembly of transient clusters on scaffold proteins and subsequent transfer of pre-formed clusters to apo proteins. A molecular level understanding of the complex processes of Fe–S cluster assembly and transfer is now beginning to emerge from the combination of in vivo and in vitro approaches. The present review highlights recent developments in understanding the mechanism of Fe–S cluster assembly and transfer involving the ubiquitous U-type scaffold proteins and the potential roles of accessory proteins such as Nfu proteins and monothiol glutaredoxins in the assembly, storage or transfer of Fe–S clusters.
The metal centres of particulate methane mono-oxygenase
Authors: Rosenzweig Amy C.
Published: December 2008

pMMO (particulate methane mono-oxygenase) is an integral membrane metalloenzyme that catalyses the oxidation of methane to methanol. The pMMO metal active site has not been identified, precluding detailed investigation of the reaction mechanism. Models for the metal centres proposed by various research groups have evolved as crystallographic and spectroscopic data have become available. The present review traces the evolution of these active-site models before and after the 2005 Methylococcus capsulatus (Bath) pMMO crystal structure determination.
Structural and functional comparison of 2-His- 1-carboxylate and 3-His metallocentres in non-haem iron(II)-dependent enzymes
Authors: Leitgeb Stefan , Nidetzky Bernd
Published: December 2008

The canonical structural motif for co-ordination of non-haem ferrous iron in metal-dependent oxygenases is a facial triad of two histidine residues and one aspartate or glutamate residue. This so-called 2-His-1-carboxylate metallocentre is often accommodated in a double-stranded β-helix fold with the iron-co-ordinating residues located in the rigid core structure of the protein. At the sequence level, the metal ligands are arranged in a HXD/E…H motif (where the distance between the conserved histidine residues is variable). Interestingly, cysteine dioxygenase, among a growing number of other iron(II) oxygenases, has the carboxylate residue replaced by another histidine. In the present review, we compare the properties of 3-His and 2-His-1-carboxylate sites based on current evidence from high-resolution crystal structures, spectroscopic characterization of the metal centres and results from mutagenesis studies. Although the overall conformation of the two metal sites is quite similar, the carboxylate residue seems to accommodate a slightly closer co-ordination distance than the counterpart histidine. The ability of the 2-His-1-carboxylate site to fit a site-directed substitution by an alternatively co-ordinating or non-co-ordinating residue with retention of metal-binding capacity and catalytic function varies among different enzymes. However, replacement by histidine disrupted the activity in the three iron(II) oxygenases examined so far.
Regulation of B-cell differentiation by microRNAs and RNA-binding proteins
Authors: Ademokun Alexander , Turner Martin
Published: December 2008

Post-transcriptional control of gene expression is an important mechanism for maintaining cellular homoeostasis and regulating the immune response to infection. It allows control of mRNA abundance, translation and localization. Mechanisms for post-transcriptional control involve RNA-binding proteins and miRNAs (microRNAs). The TTP(tristetraprolin) family of proteins recognize and bind AU-rich elements. Deletion of TTP led to a systemic autoimmune syndrome with excess circulating TNFα (tumour necrosis factor α) and GM-CSF (granulocyte/macrophage colony-stimulating factor) due to aberrantly stabilized mRNA. The family may also have a role in control of lymphocyte development and function. miRNAs regulate gene expression by promoting decay or inhibiting translation of transcripts with base pair complementarity. The importance of miRNAs in lymphocytes is highlighted by the T-cell-specific deletion of Dicer, an enzyme required for miRNA-mediated processing and from the phenotype of bic (B-cell integration cluster)/miR-155 (miRNA 155)-deficient mice.
Target site effects in the RNA interference and microRNA pathways
Authors: Obernosterer Gregor , Tafer Hakim , Martinez Javier
Published: December 2008

In RNAi (RNA interference), siRNAs (small interfering RNAs) are loaded into the RISC (RNA-induced silencing complex), which then mediates endonucleolytic cleavage of complementary target RNAs. Although RNAi has become one of the most powerful tools in molecular biology to assess gene function, there remains a great number of ineffective siRNAs. It is already known that the assembly and activation of RISC is a crucial determinant of RNAi activity, but downstream effects such as target accessibility have not been analysed extensively. Therefore we assessed the effect of target site accessibility and found that it significantly improves the potency of siRNAs. Similarly, miRNAs (microRNAs) act by repressing protein synthesis through imperfect base-pairing to the 3′-UTR (untranslated region) of target mRNAs. We found that predicted target sites reside in regions of high accessibility and tested whether this criterion could be used in the search of functional miRNA targets. In addition, we performed reporter gene assays to test whether accessibility correlates with measured mRNA suppression levels. The results of our initial study suggest that secondary structures might add a so far underrepresented layer of complexity in the recognition of RNA targets by miRNAs.
The role of Dcytb in iron metabolism: an update
Authors: McKie Andrew T.
Published: December 2008

Dcytb (duodenal cytochrome b) is an iron-regulated ferric reductase highly expressed in duodenal enterocytes. Its location and strong regulation by iron has indicated it plays an important role in iron absorption. Expression of Dcytb in cells (Caco-2 and MDCK) was found to increase both ferric reductase activity and stimulate uptake of 59Fe. An additional increase in cupric reductase activity was found in MDCK (Madin–Darby canine kidney) cells expressing Dcytb. Expression and purification of Dcytb in insect cells reveals that Dcytb is a di-haem protein and that the haems are reducible by ascorbate, indicating that ascorbate is the likely intracelluar electron donor. Studies underway in Dcytb-knockout mice reveal that Dcytb is the only iron-regulated ferric reductase in the duodenal mucosa and that loss of Dcytb affects iron absorption.
Zinc-controlled gene expression by metal-regulatory transcription factor 1 (MTF1) in a model vertebrate, the zebrafish
Authors: Hogstrand Christer , Zheng Dongling , Feeney Graham , Cunningham Phil , Kille Peter
Published: December 2008

There is a growing appreciation for the diverse roles of zinc as a signalling substance in biological systems. Zinc signalling is brought about by changes in intracellular concentrations of labile Zn2+, resulting in both genomic and non-genomic effects. The genomic responses are largely mediated by MTF1 (metal-regulatory transcription factor 1), which binds to MREs (metal-response elements) in the 5′ regulatory region of genes in response to zinc. Treatment of cultured zebrafish ZF4 cells with siRNA (small interfering RNA) to MTF1 changed the transcriptional response to zinc for over 1000 genes, as assessed using an oligonucleotide microarray. From this primary list of MTF1-dependent genes, we identified a relatively small cohort that showed a configuration of MREs in their 5′ regulatory regions similar to known MTF1 targets. This group showed a remarkable dominance of nucleic acid-binding proteins and other proteins involved in embryological development, implicating MTF1 as a master regulator of gene expression during development.
Metal-dependent generation of reactive oxygen species from amyloid proteins implicated in neurodegenerative disease
Authors: Allsop David , Mayes Jennifer , Moore Susan , Masad Atef , Tabner Brian J.
Published: December 2008

Using a method based on ESR spectroscopy and spin-trapping, we have shown that Aβ (amyloid β-peptide) (implicated in Alzheimer's disease), α-synuclein (implicated in Parkinson's disease), ABri (British dementia peptide) (responsible for familial British dementia), certain toxic fragments of the prion protein (implicated in the transmissible spongiform encephalopathies) and the amylin peptide (found in the pancreas in Type 2 diabetes mellitus) all have the common ability to generate H2O2in vitro. Numerous controls (reverse, scrambled and non-toxic peptides) lacked this property. We have also noted a positive correlation between the ability of the various proteins tested to generate H2O2 and their toxic effects on cultured cells. In the case of Aβ and ABri, we have shown that H2O2 is generated as a short burst during the early stages of aggregation and is associated with the presence of protofibrils or oligomers, rather than mature fibrils. H2O2 is readily converted into the aggressive hydroxyl radical by Fenton chemistry, and this extremely reactive radical could be responsible for much of the oxidative damage seen in all of the above disorders. We suggest that the formation of a redox-active complex involving the relevant amyloidogenic protein and certain transition-metal ions could play an important role in the pathogenesis of several different protein misfolding disorders.
Iron and calcium in the central nervous system: a close relationship in health and sickness
Authors: Pelizzoni Ilaria , Macco Romina , Zacchetti Daniele , Grohovaz Fabio , Codazzi Franca
Published: December 2008

Iron and calcium are required for general cellular functions, as well as for specific neuronal-related activities. However, a pathological increase in their levels favours oxidative stress and mitochondrial damage, leading to neuronal death. Neurodegeneration can thus be determined by alterations in ionic homoeostasis and/or pro-oxidative–antioxidative equilibrium, two conditions that vary significantly in different kinds of brain cell and also with aging. In the present review, we re-evaluate recent data on NTBI (non-transferrin bound iron) uptake that suggest a strict interplay with the mechanisms of calcium control. In particular, we focus on the use of common entry pathways and on the way cytosolic calcium can modulate iron entry and determine its intracellular accumulation.
Role of transition metals in the pathogenesis of amyotrophic lateral sclerosis
Authors: Vonk Willianne I.M. , Klomp Leo W.J.
Published: December 2008

ALS (amyotrophic lateral sclerosis) is a devastating progressive neurodegenerative disorder resulting in selective degeneration of motor neurons in brain and spinal cord and muscle atrophy. In approx. 2% of all cases, the disease is caused by a mutation in the Cu,Zn-superoxide dismutase (SOD1) gene. The transition metals zinc and copper regulate SOD1 protein stability and activity, and disbalance of the homoeostasis of these metals has therefore been implicated in the pathogenesis of ALS. Recent data strengthen the hypothesis that these transition metals are excellent potential targets to develop an effective therapy for ALS.
Functions of the nuclear envelope and lamina in development and disease
Authors: Cohen Tatiana V. , Hernandez Lidia , Stewart Colin L.
Published: December 2008

Recent findings that some 24 inherited diseases and anomalies are caused by defects in proteins of the NE (nuclear envelope) and lamina have resulted in a fundamental reassessment of the functions of the NE and underlying lamina. Instead of just regarding the NE and lamina as a molecular filtering device, regulating the transfer of macromolecules between the cytoplasm and nucleus, we now envisage the NE/lamina functioning as a key cellular ‘hub’ in integrating critical functions that include chromatin organization, transcriptional regulation, mechanical integrity of the cell and signalling pathways, as well as acting as a key component in the organization and function of the cytoskeleton.
A new model for nuclear lamina organization
Authors: Goldberg Martin W. , Fiserova Jindriska , Huttenlauch Irm , Stick Reimer
Published: December 2008

Lamins are intermediate filament proteins that form a network lining the inner nuclear membrane. They provide mechanical strength to the nuclear envelope, but also appear to have many other functions as reflected in the array of diseases caused by lamin mutations. Unlike other intermediate filament proteins, they do not self-assemble into 10 nm filaments in vitro and their in vivo organization is uncertain. We have recently re-examined the organization of a simple B-type lamina in Xenopus oocytes [Goldberg, Huttenlauch, Hutchison and Stick (2008) J. Cell Sci. 121, 215–225] and shown that it consists of tightly packed 8–10 nm filaments with regular cross-connections, tightly opposed to the membrane. When lamin A is expressed in oocytes, it forms organized bundles on top of the B lamina. This has led to a new model for lamina organization which is discussed in the present paper.
Lamin A: a putative colonic epithelial stem cell biomarker which identifies colorectal tumours with a more aggressive phenotype
Authors: Willis Naomi D. , Wilson Robert G. , Hutchison Christopher J.
Published: December 2008

Abnormalities in the expression, distribution and structural organization of A-type lamins are most commonly associated with a spectrum of inherited disorders which predominantly affect mesenchymal lineages, collectively known as laminopathies. However, a new role for lamin A has been discovered in the progression of a common epithelial cancer. CRC (colorectal cancer) patients expressing lamin A/C in their tumour tissue were found to have a 2-fold greater risk of CRC-related mortality compared with patients with lamin A/C-negative tumours. Consequently, lamin A/C is a prognostic biomarker in CRC. In vitro studies suggest that lamin A is an upstream regulator of a pathway linking actin dynamics to loss of cell adhesion, leading to enhanced cell motility and consequently increased invasive potential within a tumour. The finding that lamin A is a putative colonic epithelial stem cell biomarker suggests that the poor outcome associated with lamin A/C-positive tumours may be reflective of a more stem-cell-like phenotype. The present review discusses the link between lamin A expression and tumour progression in one of the commonest causes of cancer-related death in the Western world.
Nuclear motors and nuclear structures containing A-type lamins and emerin: is there a functional link?
Authors: Mehta Ishita S. , Elcock Lauren S. , Amira Manelle , Kill Ian R. , Bridger Joanna M.
Published: December 2008

Rapid interphase chromosome territory repositioning appears to function through the action of nuclear myosin and actin, in a nuclear motor complex. We have found that chromosome repositioning when cells leave the cell cycle is not apparent in cells that have mutant lamin A or that are lacking emerin. We discuss the possibility that there is a functional intranuclear complex comprising four proteins: nuclear actin, lamin A, emerin and nuclear myosin. If any of the components are lacking or aberrant, then the nuclear motor complex involved in moving chromosomes or genes will be dysfunctional, leading to an inability to move chromosomes in response to signalling events.
Crystallography and protein–protein interactions: biological interfaces and crystal contacts
Authors: Kobe Bostjan , Guncar Gregor , Buchholz Rebecca , Huber Thomas , Maco Bohumil , Cowieson Nathan , Martin Jennifer L. , Marfori Mary , Forwood Jade K.
Published: December 2008

Crystallography is commonly used for studying the structures of protein–protein complexes. However, a crystal structure does not define a unique protein–protein interface, and distinguishing a ‘biological interface’ from ‘crystal contacts’ is often not straightforward. A number of computational approaches exist for distinguishing them, but their error rate is high, emphasizing the need to obtain further data on the biological interface using complementary structural and functional approaches. In addition to reviewing the computational and experimental approaches for addressing this problem, we highlight two relevant examples. The first example from our laboratory involves the structure of acyl-CoA thioesterase 7, where each domain of this two-domain protein was crystallized separately, but both yielded a non-functional assembly. The structure of the full-length protein was uncovered using a combination of complementary approaches including chemical cross-linking, analytical ultracentrifugation and mutagenesis. The second example involves the platelet glycoprotein Ibα–thrombin complex. Two groups reported the crystal structures of this complex, but all the interacting interfaces differed between the two structures. Our computational analysis did not fully resolve the reasons for the discrepancies, but provided interesting insights into the system. This review highlights the need to complement crystallographic studies with complementary experimental and computational approaches.