bluuebunny/crossref_metadata_2025 huggingface dataset:
A redox-active FKBP-type immunophilin functions in accumulation of the photosystem II supercomplex in
Arabidopsis thaliana
Authors: Lima Amparo , Lima Santiago , Wong Joshua H. , Phillips Robert S. , Buchanan Bob B. , Luan Sheng
Published: August 2006

Photosystem II (PSII) catalyzes the first of two photosynthetic reactions that convert sunlight into chemical energy. Native PSII is a supercomplex consisting of core and light-harvesting chlorophyll proteins. Although the structure of PSII has been resolved by x-ray crystallography, the mechanism underlying its assembly is poorly understood. Here, we report that an immunophilin of the chloroplast thylakoid lumen is required for accumulation of the PSII supercomplex in
Arabidopsis thaliana
. The immunophilin, FKBP20-2, belongs to the FK-506 binding protein (FKBP) subfamily that functions as peptidyl-prolyl isomerases (PPIases) in protein folding. FKBP20-2 has a unique pair of cysteines at the C terminus and was found to be reduced by thioredoxin (Trx) (itself reduced by NADPH by means of NADP-Trx reductase). The FKBP20-2 protein, which contains only two of the five amino acids required for catalysis, showed a low level of PPIase activity that was unaffected on reduction by Trx. Genetic disruption of the
FKBP20-2
gene resulted in reduced plant growth, consistent with the observed lower rate of PSII activity determined by fluorescence (using leaves) and oxygen evolution (using isolated chloroplasts). Analysis of isolated thylakoid membranes with blue native gels and immunoblots showed that accumulation of the PSII supercomplex was compromised in mutant plants, whereas the levels of monomer and dimer building blocks were elevated compared with WT. The results provide evidence that FKBP20-2 participates specifically in the accumulation of the PSII supercomplex in the chloroplast thylakoid lumen by means of a mechanism that has yet to be determined.
Finding neuroelectric activity under magnetic-field oscillations (NAMO) with magnetic resonance imaging
in vivo
Authors: Truong Trong-Kha , Song Allen W.
Published: August 2006

Neuroimaging techniques are among the most important tools for investigating the function of the human nervous system and for improving the clinical diagnosis of neurological disorders. However, most commonly used techniques are limited by their invasiveness or their inability to accurately localize neural activity in space or time. Previous attempts at using MRI to directly image neuroelectric activity
in vivo
through the detection of magnetic field changes induced by neuronal currents have been challenging because of the extremely small signal changes and confounding factors such as hemodynamic modulations. Here we describe an MRI technique that uses oscillating magnetic field gradients to significantly amplify and detect the Lorentz effect induced by neuroelectric activity, and we demonstrate its effectiveness in imaging sensory nerve activation
in vivo
in the human median nerve during electrical stimulation of the wrist. This direct, real-time, and noninvasive neuroimaging technique may potentially find broad applications in neurosciences.
Transforming properties of
YAP
, a candidate oncogene on the chromosome 11q22 amplicon
Authors: Overholtzer Michael , Zhang Jianmin , Smolen Gromoslaw A. , Muir Beth , Li Wenmei , Sgroi Dennis C. , Deng Chu-Xia , Brugge Joan S. , Haber Daniel A.
Published: August 2006

In a screen for gene copy-number changes in mouse mammary tumors, we identified a tumor with a small 350-kb amplicon from a region that is syntenic to a much larger locus amplified in human cancers at chromosome 11q22. The mouse amplicon contains only one known gene,
Yap
, encoding the mammalian ortholog of
Drosophila
Yorkie (Yki), a downstream effector of the Hippo(Hpo)–Salvador(Sav)–Warts(Wts) signaling cascade, recently identified in flies as a critical regulator of cellular proliferation and apoptosis. In nontransformed mammary epithelial cells, overexpression of human
YAP
induces epithelial-to-mesenchymal transition, suppression of apoptosis, growth factor-independent proliferation, and anchorage-independent growth in soft agar. Together, these observations point to a potential oncogenic role for
YAP
in 11q22-amplified human cancers, and they suggest that this highly conserved signaling pathway identified in
Drosophila
regulates both cellular proliferation and apoptosis in mammalian epithelial cells.
The mitochondrial protein Bak is pivotal for gliotoxin-induced apoptosis and a critical host factor of Aspergillus fumigatus virulence in mice
Authors: Pardo Julian , Urban Christin , Galvez Eva M. , Ekert Paul G. , Müller Uwe , Kwon-Chung June , Lobigs Mario , Müllbacher Arno , Wallich Reinhard , Borner Christoph , Simon Markus M.
Published: August 2006

Aspergillus fumigatus infections cause high levels of morbidity and mortality in immunocompromised patients. Gliotoxin (GT), a secondary metabolite, is cytotoxic for mammalian cells, but the molecular basis and biological relevance of this toxicity remain speculative. We show that GT induces apoptotic cell death by activating the proapoptotic Bcl-2 family member Bak, but not Bax, to elicit the generation of reactive oxygen species, the mitochondrial release of apoptogenic factors, and caspase-3 activation. Activation of Bak by GT is direct, as GT triggers in vitro a dose-dependent release of cytochrome c from purified mitochondria isolated from wild-type and Bax- but not Bak-deficient cells. Resistance to A. fumigatus of mice lacking Bak compared to wild-type mice demonstrates the in vivo relevance of this GT-induced apoptotic pathway involving Bak and suggests a correlation between GT production and virulence. The elucidation of the molecular basis opens new strategies for the development of therapeutic regimens to combat A. fumigatus and related fungal infections.
Meiotic cohesins modulate chromosome compaction during meiotic prophase in fission yeast
Authors: Ding Da-Qiao , Sakurai Nobuko , Katou Yuki , Itoh Takehiko , Shirahige Katsuhiko , Haraguchi Tokuko , Hiraoka Yasushi
Published: August 2006

The meiotic cohesin Rec8 is required for the stepwise segregation of chromosomes during the two rounds of meiotic division. By directly measuring chromosome compaction in living cells of the fission yeast Schizosaccharomyces pombe, we found an additional role for the meiotic cohesin in the compaction of chromosomes during meiotic prophase. In the absence of Rec8, chromosomes were decompacted relative to those of wild-type cells. Conversely, loss of the cohesin-associated protein Pds5 resulted in hypercompaction. Although this hypercompaction requires Rec8, binding of Rec8 to chromatin was reduced in the absence of Pds5, indicating that Pds5 promotes chromosome association of Rec8. To explain these observations, we propose that meiotic prophase chromosomes are organized as chromatin loops emanating from a Rec8-containing axis: the absence of Rec8 disrupts the axis, resulting in disorganized chromosomes, whereas reduced Rec8 loading results in a longitudinally compacted axis with fewer attachment points and longer chromatin loops.
Low-grade chronic inflammation in regions of the normal mouse arterial intima predisposed to atherosclerosis
Authors: Jongstra-Bilen Jenny , Haidari Mehran , Zhu Su-Ning , Chen Mian , Guha Daipayan , Cybulsky Myron I.
Published: August 2006

Atherosclerotic lesions develop in regions of arterial curvature and branch points, which are exposed to disturbed blood flow and have unique gene expression patterns. The cellular and molecular basis for atherosclerosis susceptibility in these regions is not completely understood. In the intima of atherosclerosis-predisposed regions of the wild-type C57BL/6 mouse aorta, we quantified increased expression of several proinflammatory genes that have been implicated in atherogenesis, including vascular cell adhesion molecule–1 (VCAM-1) and a relative abundance of dendritic cells, but only occasional T cells. In contrast, very few intimal leukocytes were detected in regions resistant to atherosclerosis; however, abundant macrophages, including T cells, were found throughout the adventitia (Adv). Considerably lower numbers of intimal CD68+ leukocytes were found in inbred atherosclerosis-resistant C3H and BALB/c mouse strains relative to C57BL/6 and 129; however, leukocyte distribution throughout the Adv of all strains was similar. The predominant mechanism for the accumulation of intimal CD68+ cells was continued recruitment of bone marrow–derived blood monocytes, suggestive of low-grade chronic inflammation. Local proliferation of intimal leukocytes was low. Intimal CD68+ leukocytes were reduced in VCAM-1–deficient mice, suggesting that mechanisms of leukocyte accumulation in the intima of normal aorta are analogous to those in atherosclerosis.
The in vivo pattern of AID targeting to immunoglobulin switch regions deduced from mutation spectra in msh2−/− ung−/− mice
Authors: Xue Kanmin , Rada Cristina , Neuberger Michael S.
Published: August 2006

Immunoglobulin (Ig) class switching is initiated by deamination of C→U within the immunoglobulin heavy chain locus, catalyzed by activation-induced deaminase (AID). In the absence of uracil-DNA glycosylase (UNG) and the homologue of bacterial MutS (MSH)–2 mismatch recognition protein, the resultant U:G lesions are not processed into switching events but are fixed by replication allowing sites of AID-catalyzed deamination to be identified by the resulting C→T mutations. We find that AID targets cytosines in both donor and acceptor switch regions (S regions) with the deamination domains initiating ∼150 nucleotides 3′ of the I exon start sites and extending over several kilobases (the IgH intronic enhancer is spared). Culturing B cells with interleukin 4 or interferon γ specifically enhanced deamination around Sγ1 and Sγ2a, respectively. Mutation spectra suggest that, in the absence of UNG and MSH2, AID may occasionally act at the μ switch region in an apparently processive manner, but there is no marked preference for targeting of the transcribed versus nontranscribed strand (even in areas capable of R loop formation). The data are consistent with switch recombination being triggered by transcription-associated, strand-symmetric AID-mediated deamination at both donor and acceptor S regions with cytokines directing isotype specificity by potentiating AID recruitment to the relevant acceptor S region.
The legitimacy of addiction treatment in a world of smart people
Authors: Klingemann Harald , Bergmark Anders
Published: August 2006

Aim  This paper discusses what type of legitimacy underpins addiction treatment in contemporary western societies.

Method  Broad review of the relevant literature.

Conclusions  The legitimacy of professional interventions and the future of service provision will depend largely on the relationship between the professional and the lay referral system. These in turn are intertwined with macro‐societal changes. The basic categories in this relationship are, on one hand, the idea of evidence‐based practice (i.e. the notion of using the most accurate scientific support for the choice of treatment interventions), and on the other hand the consumer perspective, which conceptualizes addiction treatment as an interactive process between the treatment provider and the consumer. The acceptance of addiction treatment depends in most cases on the client who chooses from a whole range of informal and formal problem solutions. To an extent, experts are thus controlled by their lay counterparts and need their consent to operate and succeed. This process is complicated by the trend towards evidence‐based practice, which demands transparency and rigorous procedures and carries with it the basis for distrust in expert knowledge by displaying openly that every statement of fact is open to revision, and thus, to a certain extent, characterized by uncertainty.
Enhanced recognition of facial expressions of disgust in opiate users receiving maintenance treatment
Authors: Martin Louise , Clair Joanna , Davis Paul , O’Ryan Dominic , Hoshi Rosa , Curran H. Valerie
Published: August 2006

Aims  Accurate recognition of facial expressions of emotion is critical in interpersonal interaction but is impaired in alcoholics, even after a period of abstinence. Little is known of whether other drug‐dependent populations also show these impairments. This study aimed to investigate facial expression recognition by chronic opiate users.

Design  An independent group design was used to compare 20 participants receiving opiate substitution treatment, 20 ex‐opiate users in rehabilitation (average abstinence of 6 months) and 21 unemployed healthy controls.

Measurements  The accuracy and speed of recognizing morphed emotional facial expressions were assessed using an emotional hexagon task.

Findings  Current opiate users were significantly more accurate than ex‐users at recognizing expressions of disgust. They were also generally slower than controls in recognizing all expressions, and slower than ex‐opiate users in recognizing surprise, happy and fearful expressions.

Conclusions  Opiate users in maintenance treatment show a heightened ability to recognize facial expressions of disgust. We suggest that this may reflect increased exposure to other people’s expressions of disgust and/or priming by the physical and social environments encountered by opiate‐dependent individuals. Further, opiate maintained individuals’ global slowness in processing emotional expressions may reflect the sedative effects of methadone.
Are specific dependence criteria necessary for different substances: how can research on cannabis inform this issue?
Authors: Budney Alan J.
Published: August 2006

Aims  Research on cannabis dependence is used to comment on the similarities and differences among the substance dependence disorders, and to address the issue of whether specific versus generic substance dependence diagnostic criteria might offer the most fruitful approach to diagnosis. If cannabis dependence can be diagnosed and characterized adequately using the extant generic Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM‐IV) dependence criteria, then one could argue that these diagnostic guidelines are valid and of high utility for substances with more well‐accepted dependence syndromes.

Method  A brief, selective critical review of research on cannabis withdrawal and on the validity and internal consistency of cannabis dependence as assessed via DSM criteria for cannabis dependence was performed.

Results  Findings from these reports indicate that cannabis dependence is much more similar to than different from other types of substance dependence, even with regard to withdrawal. The generic DSM‐IV dependence criteria can be applied fairly well to cannabis, and yield findings similar to that observed with other substance dependence disorders. However, across substances, the generic criteria may not discriminate cases in a manner consistent with the underlying constructs of abuse and dependence, and cross‐substance differences probably exist in the general dependence severity level and specific symptom profiles.

Conclusions  The use of generic DSM‐IV criteria appears to work as well for cannabis dependence as for other substances, yet the more important question might be as to whether we can do better by developing more sophisticated generic criteria or by using substance specific criteria.
Comorbidity of substance use with depression and other mental disorders: from Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM‐IV) to DSM‐V
Authors: Nunes Edward V. , Rounsaville Bruce J.
Published: August 2006

Aims  To arrive at recommendations for addressing co‐occurring psychiatric and substance use disorders in the development of the Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM‐V) criteria. 

Methods  Synthesis of findings of other papers from a consensus conference and from the literature on diagnosis and treatment of co‐occurring psychiatric and substance use disorders. Most of the relevant studies examine co‐occurring depression.

Results  The diagnosis and treatment of psychiatric syndromes that co‐occur with substance use disorders has been a source of controversy, fueled in part by limitations of pre‐DSM‐IV nosologies. The DSM‐IV scheme of classifying co‐occurring disorders as primary (also referred to as independent) or substance‐induced has promise in terms of good predictive validity, although pertinent longitudinal and treatment studies are limited. The substance‐induced category answers the need of clinicians for a way to categorize patients with clinically significant psychiatric symptoms that occur in the setting of ongoing substance use.

Conclusions  DSM‐V should retain the primary (independent) and substance‐induced categories. In DSM‐IV these categories are broadly defined and leave much to clinical judgement. Existing data sets should be brought to bear to refine the criteria, making them more detailed with clearer anchor points and more specificity around particular substances and psychiatric syndromes. More longitudinal studies and clinical trials are also needed. Looking beyond DSM‐V, co‐occurring psychiatric syndromes are likely to be important in the quest for a nosology founded on pathophysiology.
Adolescents and substance‐related disorders: research agenda to guide decisions on Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM‐V)
Authors: Crowley Thomas J.
Published: August 2006

Aims  Since the publication of the Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM‐IV), many studies have addressed substance use disorders (SUD) in adolescents. Based on that adolescent literature, this paper suggests further research to help guide decisions about revising for DSM‐V the SUD criteria in DSM‐IV.

Method  The author has reviewed the ‘Substance Related Disorders’ section of DSM‐IV‐TR, recalled his experience in helping to draft that section, accessed relevant articles in PubMed and reviewed his own extensive file of literature citations.

Results  This paper suggests six questions for adolescent research to help guide the framers of DSM‐V’s ‘Substance Related Disorders’ section: (a) DSM‐IV did not provide a diagnosis of cannabis withdrawal; should DSM‐V continue that position? (b) Should SUD be included or referenced among ‘Disorders Usually First Diagnosed in Infancy, Childhood, or Adolescence’? (c) Can inter‐rater reliability of the substance abuse (SA) criteria be improved with altered example situations, text descriptions or phrasing of the current criteria? (d) Between ages 14 and 18 years is earlier onset of SUD a severity marker that could be incorporated into DSM‐V as a predictor of worse course? (e) In DSM‐V could a phenotypic descriptor of pathological multi‐substance involvement document severity and predict course of SUD? (f) Could clinicians and patients benefit from DSM‐V‐related postpublication procedures for classifying emerging new drugs into DSM‐V’s categories?

Conclusion  Without substantive changes in SA or substance dependence diagnostic criteria, research may improve the usefulness of those criteria for adolescents.
Subtypes of substance dependence and abuse: implications for diagnostic classification and empirical research
Authors: Babor Thomas F. , Caetano Raul
Published: August 2006

Aims  To evaluate the relevance of a form of diagnostic classification called clinical subtyping in relation to possible revisions in the diagnostic criteria for substance abuse and dependence in psychiatric classification systems.

Methods  A general rationale for subtyping is presented. To explore the implications for diagnostic classification, recent research on a variety of subtyping schemes is reviewed in terms of the development of new subtypes and the validation of established theories.

Results  Subtypes of alcoholism and other psychiatric disorders have been proposed since the beginning of modern psychiatry. Recent subtyping research suggests that no consensus has emerged about the nature, much less the number, of subtypes that could be used to characterize the clinical heterogeneity assumed to be present in groups of people with substance use disorders. Although several relatively simple binary typologies have been developed (e.g. Cloninger’s type I and type II; Babor et al.’s type A and type B), validation research has produced mixed results in terms of the construct, concurrent and predictive validity of these classifications.

Conclusions  The adoption of a subtyping scheme in the major psychiatric classification systems is not recommended until further international research is conducted.
Taking account of cultural and societal influences on substance use diagnoses and criteria
Authors: Room Robin
Published: August 2006

Aims This article reviews the problems of cross‐cultural applicability, which have been identified at the level of instrument items, at the level of criteria, and at the level of concepts and diagnoses. One near‐universal appears to be that the diagnoses carry a weight of moral judgement and often of social stigma, whatever the clinician’s intentions.

Methods The findings of studies on variations between cultures in the meaningfulness and meaning of the main substance use diagnoses and criteria are described.

Results Suggestions are made for directions of thinking and work to improve the cross‐cultural applicability of five current diagnoses: intoxication, withdrawal, harmful use, abuse and dependence.

Conclusion It is argued that the possibility should be held open of bounded applicability of some diagnoses or criteria, in some societies but not in others.
Cultural issues and psychiatric diagnosis: providing a general background for considering substance use diagnoses
Authors: Escobar Javier I. , Vega William A.
Published: August 2006

Aims  To establish a general context on the topic of cross‐cultural diagnosis and suggest how it can be applied to substance use disorders.

Methods  Critical reviews of the literature on psychiatric diagnosis, cross‐cultural issues and the concept of ethnicity were conducted to provide a framework for making specific recommendations for substance use diagnoses.

Results  Cross‐cultural diagnosis remains in a state of flux. Key questions on ethnicity and psychopathology have not yet been fully answered by existing research. The broad use of the Diagnostic and Statistical Manual for Mental Disorders (DSM) system world‐wide requires a careful look at its cross‐cultural applicability.

Conclusion  For DSM‐V, cultural/ethnic issues have to be clearly defined in clear terms that lend themselves to operational definitions. Recommendations should be research‐based and testable. Meaningful cultural annotations and a glossary of cultural terms that are applicable in daily clinical practice and not limited to less frequently encountered syndromes (culture‐bound) would be highly desirable.
Diagnosis of alcohol dependence in epidemiological surveys: an epidemic of youthful alcohol dependence or a case of measurement error?
Authors: Caetano Raul , Babor Thomas F.
Published: August 2006

Aims  To review the literature on the prevalence of alcohol dependence according to age, presenting data suggesting that the increased prevalence of alcohol dependence among young adults may be inflated because of measurement error.

Design  Household surveys with random selection of respondents.

Setting  General population.

Participants  Survey respondents 12 years of age and older.

Measurements  Alcohol dependence.

Findings  Data for male current drinkers show that 4.6% of adolescents (aged 12–17 years) meet criteria for past year dependence, and the rate increases to 8.5% in the 18–23 age group, decreasing thereafter. Symptom level prevalence estimates indicate that younger age groups report higher rates of tolerance and withdrawal symptoms than older age groups.

Conclusion  Young adults may be reporting tolerance and withdrawal symptoms partly because the wording of structured interview schedules leads to confusion of binge drinking and its sequelae with physical symptoms of alcohol dependence. There is a need to examine whether young adults are confusing the sequelae of acute intoxication with alcohol withdrawal, and rapid initial tolerance with the classical tolerance reported by alcoholics. Epidemiologists and clinicians need to be cautious of the tendency of structured psychiatric interviews to classify young adults as being alcohol‐dependent. It may be useful to characterize individuals who meet alcohol dependence criteria at a young age (e.g. prior to age 25 years) as manifesting a form of ‘adolescent alcohol dependence’, which may represent a less severe form of alcohol use disorder than that observed in adults.
The development of a research agenda for substance use disorders diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM‐V)
Authors: Saunders John B. , Schuckit Marc A.
Published: August 2006

Aims  This paper describes the background to the establishment of the Substance Use Disorders Workgroup, which was charged with developing the research agenda for the development of the next edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM). It summarizes 18 articles that were commissioned to inform that process.

Methods  A preliminary list of research topics, developed at the DSM‐V Launch Conference in 2004, led to the identification of subjects that were subject to formal presentations and detailed discussion at the Substance Use Disorders Conference in February 2005.

Results  The 18 articles presented in this supplement examine: (1) categorical versus dimensional diagnoses; (2) the neurobiological basis of substance use disorders; (3) social and cultural perspectives; (4) the crosswalk between DSM‐IV and the International Classification of Diseases Tenth Revision (ICD‐10); (5) comorbidity of substance use disorders and mental health disorders; (6) subtypes of disorders; (7) issues in adolescence; (8) substance‐specific criteria; (9) the place of non‐substance addictive disorders; and (10) the available research resources.

Conclusions  In the final paper a broadly based research agenda for the development of diagnostic concepts and criteria for substance use disorders is presented.
The island rule and a research agenda for studying ecogeographical patterns
Authors: Lomolino Mark V. , Sax Dov F. , Riddle Brett R. , Brown James H.
Published: August 2006

We are currently experiencing a resurgence of interest in ecogeographical rules, which describe general trends in morphology and related traits along geographical gradients. In order to develop a more comprehensive understanding of the generality and underlying causal mechanisms for these patterns, we recommend a new, more integrated research agenda. In particular, we recommend studies that simultaneously consider different clines in morphology, geographical ranges and diversity as intricately related phenomena; all being ecological, evolutionary and biogeographical responses of organisms to selection regimes that vary non‐randomly over space and time, and among species with different ecological and evolutionary histories.
The management of ectodermal dysplasia and severe hypodontia. International conference statements
Authors: HOBKIRK J. A. , NOHL F. , BERGENDAL B. , STORHAUG K. , RICHTER M. K.
Published: August 2006

summary  An international conference on ectodermal dysplasias and hypodontia, held in London in 2004, featured a session devoted to the management of the ectodermal dysplasias and severe hypodontia. This paper presents a set of statements prepared by an international specialist panel, including representatives of patient support groups, who presented and subsequently debated a series of papers on this subject. The following topics were explored: potential roles of patient support groups; core care standards, including the roles and composition of medical and dental multidisciplinary teams for treating these conditions; the format of a baseline data set for patients with an ED; and priorities for research in ectodermal dysplasias, with particular regard to laboratory and clinical studies, and research methodology. The statements are intended to form an international framework for developing patient care pathways, and collaborative research in this field.
The European Sero‐Epidemiology Network 2: standardization of assay results for hepatitis B virus
Authors: Kafatos G. , Anastassopoulou C. , Nardone A. , Andrews N. , Barbara C. , Boot H. J. , Butur D. , Davidkin I. , Gelb D. , Griskevicius A. , Hesketh L. , Icardi G. , Jones L. , Kra‐Oz Z. , Miller E. , Mossong J. , Nemecek V. , De Ory F. , Sobotová Z. , Thierfelder W. , Van Damme P. , Hatzakis A.
Published: August 2006

Summary.  The aim of the European Sero‐Epidemiology Network 2 was to coordinate and standardize the serological surveillance of vaccine‐preventable diseases in Europe. In this study, the standardization of hepatitis B virus (HBV) results is described. The 15 participating national laboratories tested a unique panel of 172 sera established by the Greek reference centre for HBV surface antigen (HBsAg), antibodies to HBsAg (anti‐HBs) and/or to the HBV core antigen (anti‐HBc) by assay methods of their choice. Country‐specific quantitative measurements for anti‐HBs and anti‐HBc were transformed into common units using standardization equations derived by regressing each country's panel results against the reference centre's results, thus adjusting for interassay and interlaboratory variability. For HBsAg, a qualitative analysis (positive/negative) showed at least 99% agreement with the reference laboratory for all countries. By combining these standardized and qualitative results for the markers mentioned earlier, it was possible to achieve comparable estimates of the proportion of the population susceptible to HBV, vaccinated against HBV, with a past HBV infection, and with a current infection or chronic carrier state. Standardization is a very important tool that allows for international serological comparisons to assess the current vaccination policies and the progress of HBV control in Europe.
Difference in T helper responses during hepatitis flares in hepatitis B e antigen (HBeAg)‐positive patients with genotypes B and C: implication for early HBeAg seroconversion
Authors: Yuen M.‐F. , Wong D.K‐.H , Zheng B.‐J. , Chan C.C‐.S. , Yuen J.C‐.H. , Wong B.C‐.Y. , Lai C.‐L.
Published: August 2006

Summary.  The underlying mechanisms for earlier hepatitis B e antigen (HBeAg) seroconversion in patients with chronic hepatitis B virus (HBV) genotype B when compared with genotype C are unknown. We aimed to determine whether there were any differences in the T helper (Th) responses during hepatitis flares in HBeAg‐positive patients with genotypes B and C. Proliferative response measured by 3H‐thymidine uptake and Th responses measured by Enzyme‐Linked Immunosorbent Spot assays for interleukin (IL)‐2, interferon‐gamma (IFN‐γ), IL‐4, IL‐5 and IL‐10 were performed in 10 patients with genotype B and 10 with genotype C with hepatitis flares. HBV genotypes, core promoter, precore mutations, sequence of HBV core region and HBV DNA levels were determined. There was no difference in the HBV DNA levels during hepatitis flares between patients with genotypes B and C. Patients with genotype B had a significantly higher number of IFN‐γ producing cells [with hepatitis B core antigen (HBcAg) stimulation] and lower number of IL‐10 producing cells (with HBcAg and HBeAg stimulation) compared with patients with genotype C (P = 0.011, =0.043, <0.001 respectively). There was a trend (P = 0.058) that patients with genotype B had a higher cumulative rate of HBeAg seroconversion. Patients with precore mutants also had a significantly higher number of IFN‐γ producing cells (with HBcAg stimulation) and lower number of IL‐10 producing cells (with HBeAg stimulation) compared to patients without precore mutant (P = 0.038, =0.016 respectively). HBV genotype B induces a greater Th1 and lesser Th2 response than genotype C. This provides immunologic evidence for the higher chance of HBeAg seroconversion in patients with genotype B.
MAMPs and MIMPs: proposed classifications for inducers of innate immunity
Authors: Mackey David , McFall Aidan J.
Published: August 2006

Plants encode a sophisticated innate immune system. Resistance against potential pathogens often relies on active responses. Prerequisite to the induction of defences is recognition of the pathogenic threat. Significant advances have been made in our understanding of the non‐self molecules that are recognized by plants and the means by which plants perceive them. Established terms describing these recognition events, including microbe‐associated molecular pattern (MAMP), MAMP‐receptor, effector, and resistance (R) protein, need clarification to represent our current knowledge adequately. In this review we propose criteria to classify inducers of plant defence as either MAMPs or microbe‐induced molecular patterns (MIMPs). We refine the definition of MAMP to mean a molecular sequence or structure in ANY pathogen‐derived molecule that is perceived via direct interaction with a host defence receptor. MIMPs are modifications of host‐derived molecules that are induced by an intrinsic activity of a pathogen‐derived effector and are perceived by a host defence receptor. MAMP‐receptors have previously been classified separately from R‐proteins as a discrete class of surveillance molecules. However, MAMP‐receptors and R‐proteins cannot be distinguished on the basis of their protein structures or their induced responses. We propose that MAMP‐receptors and MIMP‐receptors are each a subset of R‐proteins. Although our review is based on examples from plant pathogens and plants, the principles discussed might prove applicable to other organisms.
Regular cellular distribution of plasmids by oscillating and filament‐forming ParA ATPase of plasmid pB171
Authors: Ebersbach Gitte , Ringgaard Simon , Møller‐Jensen Jakob , Wang Qing , Sherratt David J. , Gerdes Kenn
Published: August 2006

Centromere‐like loci from bacteria segregate plasmids to progeny cells before cell division. The ParA ATPase (a MinD homologue) of the par2 locus from plasmid pB171 forms oscillating helical structures over the nucleoid. Here we show that par2 distributes plasmid foci regularly along the length of the cell even in cells with many plasmids. In vitro, ParA binds ATP and ADP and has a cooperative ATPase activity. Moreover, ParA forms ATP‐dependent filaments and cables, suggesting that ParA can provide the mechanical force for the observed regular distribution of plasmids. ParA and ParB interact with each other in a bacterial two‐hybrid assay but do not interact with FtsZ, eight other essential cell division proteins or MreB actin. Based on these observations, we propose a simple model for how oscillating ParA filaments can mediate regular cellular distribution of plasmids. The model functions without the involvement of partition‐specific host cell receptors and is thus consistent with the striking observation that partition loci can function in heterologous host organisms.
Involvement of Clp protease activity in modulating the Bacillus subtilisσW stress response
Authors: Zellmeier Stephan , Schumann Wolfgang , Wiegert Thomas
Published: August 2006

The induction of Bacillus subtilis genes controlled by the extracytoplasmic function alternative sigma factor σW is strongly impaired in a strain deleted for the ClpP peptidase gene and in a double knockout of the ClpX and ClpE ATPase genes. Truncated soluble forms of the σW anti‐sigma factor RsiW are stabilized in a clpP minus strain as revealed by the green fluorescent reporter protein fused to the N‐terminus of RsiW and by pulse‐chase experiments. Conserved alanine residues are present in the transmembrane region of RsiW, and mutations in these positions abolish induction of σW‐controlled genes. Following alkaline shock, a truncated cytoplasmic form of RsiW is detectable in a strain expressing a triple alanine mutant allele of rsiW. These data point to a mechanism where the trans‐membrane segment of RsiW contains a cryptic proteolytic tag that is uncovered as a result of intramembrane proteolysis of RsiW by RasP (YluC). After RasP‐clipped RsiW is detached from the membrane, this proteolytic tag becomes crucial for the complete degradation of RsiW by cytoplasmic proteases and the release of σW. ClpXP plays a major role in this third proteolytic step of stress‐induced degradation of RsiW. Overexpression of SsrA‐tagged green fluorescent protein as a ClpXP substrate protein reduces alkali induction of a σW‐controlled gene by a factor of about three, indicating that a titration mechanism is able to tune the σW‐mediated stress response to the cellular state.
Differential microglial regulation in the human spinal cord under normal and pathological conditions
Authors: Stoll M. , Capper D. , Dietz K. , Warth A. , Schleich A. , Schlaszus H. , Meyermann R. , Mittelbronn M.
Published: August 2006

As the primary intrinsic immune effector cells of the central nervous system, microglia are involved in virtually all pathological processes of the brain and spinal cord including inflammatory, neurodegenerative, traumatic, neoplastic and vascular diseases. Despite this important role, there is a lack of data concerning microglial distribution and protein expression in the human spinal cord. In this study, we immunohistochemically investigated 10 normal human spinal cords to establish reference data and compared these results with 15 pathological human spinal cords deriving from distinct pathologies. Each spinal cord was evaluated at eight different levels for three white and two grey matter areas for both constitutive (MHC‐II, CD68, IL‐16, AIF‐1, LCA, CD4) and reactive (MRP‐8, MRP‐14) microglial antigens. Whereas previous studies revealed significant regional differences in microglial distribution and protein expression in human brain, normal spinal cord displayed a uniform expression pattern, reaching levels of up to 17% MHC‐II positive cells of the total cell population. This datum formed the basis for the further evaluation of microglia expression levels in pathological spinal cords, where levels of up to 45% positive cells were observed. Our results represent important reference values for future neuropathological diagnostic and therapeutical approaches in spinal cord pathologies.
Comparison of the egg‐laying behaviour and electrophysiological responses of Delia radicum and Delia floralis to cabbage leaf compounds
Authors: GOUINGUENÉ SANDRINE P. D. , STÄDLER E.
Published: August 2006

Abstract The behaviour and the sensitivity of adult cabbage root fly, Delia radicum and turnip root fly, Delia floralis are compared with host‐plant extracts and isolated crucifer compounds previously identified as oviposition stimulants for D. radicum. The oviposition behaviour of both species is similar; 7–10‐day‐old females are stimulated to lay eggs by the methanol extract of cauliflower leaves that contains thia‐triaza‐fluorenes (CIF) as well as glucosinolates. The glucosinolate fraction is mainly composed of glucobrassicin, which alone stimulate both fly species to lay eggs. The C5 and D3,4 sensilla on the prothoracic tarsae of newly‐emerged D. radicum contain neurones sensitive to the glucosinolate fractions tested and to glucobrassicin, whereas the CIF specifically stimulate a neurone in the C5 sensillum. By contrast, newly‐emerged D. floralis respond less to glucosinolates, especially to glucobrassicin, and have sensitive neurones to CIF in other sensilla than D. radicum. Recordings are also made from the longest sensilla present on the labellum because they are apparently sensitive to glucosinolates. By contrast to earlier investigations, no remarkable phasic‐tonic responses of these neurones are seen. The two species are difficult to discriminate visually, have the same host plants, show identical host‐selection behaviour, apparently respond to the same physical and chemical properties of their host‐plants, but have a clearly different distribution of receptor neurones in the tarsal sensilla.
Energetics of newly‐mated queens and colony founding in the fungus‐gardening ants Cyphomyrmex rimosus and Trachymyrmex septentrionalis (Hymenoptera: Formicidae)
Authors: SEAL JON N. , TSCHINKEL WALTER R.
Published: August 2006

Abstract The energetics of colony founding is investigated in the fungus gardening ants (Attini) Trachymyrmex septentrionalis and Cyphomyrmex rimosus. Similar to most ants, inseminated queens of these two species found nests independently unaccompanied by workers (haplometrosis). Whereas most ant founding queens seal themselves in a chamber and do not feed when producing a brood entirely from metabolic stores (claustral founding), the majority of fungus gardening ants must forage during the founding phase (semiclaustral founding). Laboratory‐reared T. septentrionalis individuals comprise 84 dealate females collected after mating flights in June 2004. Twenty are immediately killed to obtain values for queen traits and another 20 after worker emergence for queen, fungus garden and worker traits. Cyphomyrmex rimosus comprise 22 dealate females collected in June 2005; ten of which are immediately killed and similarly prepared. Newly‐mated T. septentrionalis queens have 25% of their dry weight as fat; whereas newly‐mated C. rimosus queens contain 11% fat. These amounts are 50–75% less than most independently founding ant species. Trachymyrmex septentrionalis queens lose merely 5% of their energetic content during colony founding, whereas the total energetic content of their brood is more than three‐fold the amount lost by the queen. Incipient T. septentrionalis colonies produce approximately half as much ant biomass per gram of fungus garden as do mature colonies. Similar to most ants, T. septentrionalis produces minim workers that are approximately 40% lighter than workers from mature colonies. Regardless of their size, T. septentrionalis workers contain much lower fat than do workers of claustral species. These data indicate that fungus gardening is adaptive because colonies can produce much cheaper offspring, making colony investment much lower.
Combined effect of an antifeedant α‐amylase inhibitor and a predator Cheyletus malaccensis in controlling the stored‐product mite Acarus siro
Authors: HUBERT J. , HÝBLOVÁ J. , MÜNZBERGOVÁ Z. , PEKÁR S. , KŘÍŽKOVA‐KUDLÍKOVÁ I. , DOLEČKOVÁ‐MAREŠOVÁ L. , STEJSKAL V. , MAREŠ M.
Published: August 2006

Abstract Acarus siro is the most abundant and frequent mite to infest stored‐food products, causing allergies and transmitting mycotoxin producing fungi. The predatory mite Cheyletus malaccensis is a candidate species in the biocontrol programme for this pest. In vitro, the α‐amylase inhibitor acarbose is effective against the α‐amylase of A. siro but not against that of C. malaccensis. In vivo, the impact of acarbose on a population of A. siro is investigated along with the interaction with the predator. Various densities of adult parthenogenetic females of C. malaccensis are reared on A. siro feeding on either a control diet or a diet containing different acarbose concentrations. The combined action of both factors significantly improved the final biocontrol efficiency with C. malaccensis, compensating for the lower energetic content of the prey on acarbose by increasing the number of prey caught. Acarbose had no negative effects on the longevity and the length of oviposition period of C. malaccensis but partially reduced its fecundity. The results are discussed in the context of the integrated control of stored‐product mite pests.
Phagocytosis, Production of Nitric Oxide and Pro‐inflammatory Cytokines by Macrophages in the Presence of Dematiaceus Fungi that Causes Chromoblastomycosis
Authors: Hayakawa M. , Ghosn E. E. B. , Da Gloria Teixeria de Sousa M. , Ferreira K. S. , Almeida S. R.
Published: August 2006

Chromoblastomycosis is characterized by the slow development of polymorphic skin lesions (nodules, verrucas, tumores, plaques and scar tissue). Inside the host, infectious propagules adhere to epithelial cells and differentiate into sclerotic forms, which effectively resist destruction by host effector cells and allow onset of chronic disease. A cellular immune response against fungi is essential to control infection. Amongst the cells of the immune system, macrophages play the most important role in controlling fungal growth. In this study, we show that the fungicidal characteristic of macrophages is dependent on the fungal species that causes chromoblastomycosis. We began by observing that the phagocytic index was higher for Fonsecaea pedrosoi and Rhinocladiella aquaspersa compared with that of other fungi. Complement‐mediated phagocytosis was more important for Phialophora verrucosa and R. aquaspersa and was inhibited by mannan when F. pedrosoi and R. aquaspersa conidia were phagocytosed by macrophages. We showed that macrophages killed significantly only R. aquaspersa. We also found that the phagocytosis of fungi has functional consequences for macrophages as phagocytosis resulted in down‐modulation of MHC‐II and CD80 expression as well as in the inhibition of the basal liberation of NO. However, the inhibition of the basal liberation of NO nor the down‐modulation of MHC and co‐stimulatory molecules were observed in the presence of R. aquaspersa.
Early infection of scutellum tissue with Agrobacterium allows high‐speed transformation of rice
Authors: Toki Seiichi , Hara Naho , Ono Kazuko , Onodera Haruko , Tagiri Akemi , Oka Seibi , Tanaka Hiroshi
Published: August 2006

Several approaches have recently been adopted to improve Agrobacterium‐mediated transformation of rice, both to generate the large number of T‐DNA insertion plants needed for functional analysis of the rice genome, and for production of rice with additional agronomical value. However, about 3 months of in vitro culture is still required for isolation of transgenic rice plants. Here, we report the competency of scutellum tissue from 1‐day pre‐cultured seeds for Agrobacterium‐mediated transformation. Furthermore, early infection of rice seeds with Agrobacterium enhanced efficient selection of transformed calli. Using our system, we successfully regenerated transgenic rice plantlets within a month of the start of the aseptic culture of mature seeds. Our new system should reduce the somaclonal variation accompanying prolonged culture of rice cells in the dedifferentiated state and facilitate the molecular breeding of rice.
Socially marketed insecticide‐treated nets effectively reduce Plasmodium infection and anaemia among children in urban Malawi
Authors: Mathanga Don P. , Campbell Carl H. , Taylor Terrie E. , Barlow Robin , Wilson Mark L.
Published: August 2006

Background  Use of insecticide‐treated nets (ITNs) has become a central focus for the Roll Back Malaria campaign, and many countries in Africa have now embarked on large‐scale public health programmes aimed at making ITNs available to those at greatest risk. However, the effectiveness of these programmes has rarely been evaluated.

Method  We conducted a cross‐sectional survey to assess the impact of an ITN social marketing programme on Plasmodium falciparum infection and anaemia among children in urban Malawi.

Results  Knowledge of ITNs was high; however, only 42% of the children surveyed reported to have used an ITN the previous night. Nevertheless, 17% (295/1721) of children had a positive P. falciparum smear at enrolment. Use of ITNs was associated with 52% protective efficacy against Plasmodium parasitemia. More than two‐thirds of children were anaemic, yet the mean haemoglobin concentration was significantly higher in children using ITNs than in those not using nets. ITN use was associated with wealth, as poorer households were 60% less likely to use treated nets.

Conclusion  Although ITN social marketing programmes have the potential of improving malaria control and prevention, additional efforts are required to reach those for whom even subsidized nets are still too expensive.