bluuebunny/crossref_metadata_2025 huggingface dataset:
The rising tide of fisheries instruments and the struggle to keep afloat
Authors: Cochrane Kevern L. , Doulman David J.
Published: January 2005

Since agreement was reached in 1982 on the UN Convention on the Law of the Sea, and particularly since the conclusion of the 1992 UN Conference on Environment and Development, the rate of development of global instruments impacting on fisheries has escalated considerably and is apparently continuing to do so. A flood of global and regional instruments relevant to fisheries has been generated, including, for example, the 1973 Convention on International Trade in Endangered Species of Wild Fauna and Flora which pre–dates the UN Convention, the 1992 Convention on Biological Diversity, 1992 Agenda 21: Programme of Action for Sustainable Development, the 1993 FAO Agreement to Promote Compliance with International Conservation and Management Measures by Fishing Vessels on the High Seas, the 1995 UN Agreement for the Implementation of the Provisions of the United Nations Convention on the Law of the Sea of 10 December 1982 relating to the Conservation and Management of Straddling Fish Stocks and Highly Migratory Fish Stocks, the 1995 FAO Code of Conduct for Responsible Fisheries and its four international plans of action and strategy, and the 2001 FAO Reykjavík Declaration on Responsible Fisheries in the Marine Ecosystem reflecting the growing international interest in ecosystem approaches to fisheries. Most recent has been the 2002 World Summit on Sustainable Development's Plan of Implementation. These instruments have been motivated by real problems associated with environmental degradation and living resource depletion, in several cases specifically in connection with fisheries. They have attempted to address these problems, and each instrument is recognized as being a positive contribution towards the sustainable use of resources and ecosystems. However, taken collectively they form a large, often confusing and potentially overwhelming set of recommendations and requirements that is putting many fishery management agencies under severe pressure as they seek to implement them. This paper provides a brief overview of the range of recent instruments and their implications for sustainable fisheries management, considers the progress being made in implementing them, identifies general problems being encountered and how they might be ameliorated in the future. A key problem is a lack of political will, or political ability, to address effectively the problems facing fisheries and marine ecosystems. One consequence of this is that the agencies charged with fisheries management are not provided with adequate technical and financial capacity to implement the instruments in most, if not all, countries. The problem is especially acute in developing countries where they are strained by the full effects of ‘instrument implementation fatigue’.
The role of marine reserves in achieving sustainable fisheries
Authors: Roberts Callum M. , Hawkins Julie P. , Gell Fiona R.
Published: January 2005

Many fishery management tools currently in use have conservation value. They are designed to maintain stocks of commercially important species above target levels. However, their limitations are evident from continuing declines in fish stocks throughout the world. We make the case that to reverse fishery declines, safeguard marine life and sustain ecosystem processes, extensive marine reserves that are off limits to fishing must become part of the management strategy. Marine reserves should be incorporated into modern fishery management because they can achieve many things that conventional tools cannot. Only complete and permanent protection from fishing can protect the most sensitive habitats and vulnerable species. Only reserves will allow the development of natural, extended age structures of target species, maintain their genetic variability and prevent deleterious evolutionary change from the effects of fishing. Species with natural age structures will sustain higher rates of reproduction and will be more resilient to environmental variability. Higher stock levels maintained by reserves will provide insurance against management failure, including risk–prone quota setting, provided the broader conservation role of reserves is firmly established and legislatively protected. Fishery management measures outside protected areas are necessary to complement the protection offered by marine reserves, but cannot substitute for it.
Spermatology of the genus Lepidodasys Remane, 1926 (Gastrotricha, Macrodasyida): towards a revision of the family Lepidodasyidae Remane, 1927
Authors: Guidi Loretta , Pierboni Lara , Ferraguti Marco , Todaro M. Antonio , Balsamo Maria
Published: January 2005

The spermatozoa of Lepidodasys unicarenatus and Lepidodasys sp. are filiform and composed of a cork‐screw shaped acrosome, a helical nucleus surrounding a mitochondrial axis, and a 9 × 2 + 2 flagellum as in the basic structural model of the macrodasyidan sperm. The genus Lepidodasys has a debated phylogenetic position and has been linked in turn to the family Lepidodasyidae and the family Thaumastodermatidae. The sperm features of the two Lepidodasys species examined are distinct from those typical of the two families: the absence of the periaxonemal cylinder, a character shared only with Turbanellidae among Macrodasyida, could be considered as a symplesiomorphy, suggesting a basal position of the genus along the Macrodasyida clade. Moreover, a comparison of the spermatogenic process of Lepidodasys sp. with those of Acanthodasys aculeatus (Thaumastodermatidae) and Cephalodasys maximus (Lepidodasyidae) has revealed that the process of acrosome formation and nuclear morphology during spermatogenesis are peculiar in Lepidodasys sp. and differences are evident especially in the late stages of spermatogenesis. Penetrated spermatozoa were observed in the oocytes at all maturation stages in L. unicarenatus.
Morphometry and sexual dimorphism of the coastal spotted dolphin, Stenella attenuata graffmani, from Bahía de Banderas, Mexico
Authors: Sanvicente‐Añorve Laura , López‐Sánchez José Luis , Aguayo‐Lobo Anelio , Medrano‐González Luis
Published: January 2005

External measurements and size differences between the sexes were examined in the coastal spotted dolphin, Stenella attenuata graffmani, in Bahía de Banderas, on the Mexican Pacific coast. The dolphins were collected by local fishermen and 29 external characteristics were measured by members of the Marine Mammals Laboratory, University of Mexico. The length of each characteristic with respect to total length was analysed through adjustment of the data to a power equation. A stepwise discriminant analysis was applied to the absolute values and to those expressed as proportions to analyse the differences between the sexes. Results indicate that growth in these dolphins is generally negatively allometric, and most of the characteristics measured were, in both absolute and proportional terms, greater in male dolphins than in female dolphins. As found in many species of odontocetes, the discriminant analysis showed that the main differences between the sexes for this coastal subspecies include the relative positions of the umbilicus, the genital aperture and the anus. The morphometric data provided by this study, corresponding to 29 specimens of S. a. graffmani collected in a restricted locality of the Mexican Pacific coast, are particularly interesting to studies documenting latitudinal morphological differences in the coastal spotted dolphin.
Why we can’t get along
Authors: Covington Coline
Published: January 2005

Abstract:  The author examines various arguments to explain the internal conflicts and schisms that have afflicted depth psychology since its beginnings. These arguments include the inevitable splits that occur in the course of institutional development, the inheritance of family schisms within the profession, historical, geographical and political influences, Freud's notion of the ‘narcissism of minor differences’ along with Gordon's idea of the need for enemies in establishing identity, and the impact of market forces. The author refutes these arguments and postulates instead that the profession attracts narcissistically disturbed members who have not been or cannot be sufficiently analysed. The profession needs to address this endemic narcissism in order to prevent further splitting and to establish a more ecumenical framework.
1. On note taking
Authors: Plaut Alfred B. J.
Published: January 2005

Abstract:  In this paper the author explores the theoretical and technical issues relating to taking notes of analytic sessions, using an introspective approach. The paper discusses the lack of a consistent approach to note taking amongst analysts and sets out to demonstrate that systematic note taking can be helpful to the analyst. The author describes his discovery that an initial phase where as much data was recorded as possible did not prove to be reliably helpful in clinical work and initially actively interfered with recall in subsequent sessions. The impact of the nature of the analytic session itself and the focus of the analyst's interest on recall is discussed.

The author then describes how he modified his note taking technique to classify information from sessions into four categories which enabled the analyst to select which information to record in notes. The characteristics of memory and its constructive nature are discussed in relation to the problems that arise in making accurate notes of analytic sessions.
Ethical issues in the publication of clinical material1
Authors: Wharton Barbara
Published: January 2005

Abstract:  Some of the ethical issues involved in publishing clinical material are considered. These include the ‘ownership’ of such material, the responsibilities of the analyst towards patients and professional colleagues, the keeping and status of records, the nature of trust and confidentiality and its place in analysis, the question of obtaining consent for publication, the nature of consent, and its consequences for treatment. The issues of disguise, of authenticity, and of accuracy are also touched on, as is the potential role of the author's anonymity in protecting the anonymity of the patient.
Piecemeal degranulation in human tumour pheochromocytes
Authors: Crivellato Enrico , Finato Nicoletta , Ribatti Domenico , Beltrami Carlo Alberto
Published: January 2005

Piecemeal degranulation (PMD) has been recognized in two cases of human pheochromocytoma from the adrenal medulla, which were studied by transmission electron microscopy. Tumour pheochromocytes presented a highly characteristic cytoplasmic admixture of normal resting granules, swollen granules with eroded matrices and enlarged empty containers. Chromaffin granules that appeared to be normal and altered granules maintained their individual structure, and did not fuse with each other or with the plasma membrane. In accordance with the currently accepted model for granule discharge during PMD, electron‐dense or clear vesicles 30–150 nm in diameter were seen either attached to the surface of chromaffin granules and the plasma membrane or free in the cytosol. This is the first description of PMD in human adrenal chromaffin cells and, in addition, is the first report of PMD in tumour secretory cells. These findings add further to the concept that PMD may have a broader spectrum of expression than hitherto recognized.
Microscopic anatomy of the sural nerve in the postnatal developing rat: a longitudinal and lateral symmetry study
Authors: Jeronimo André , Jeronimo Cláudia Alem Domingues , Filho Omar Andrade Rodrigues , Sanada Luciana Sayuri , Fazan Valéria Paula Sassoli
Published: January 2005

Rat sural nerve is widely used in experimental studies investigating injury and regeneration of the peripheral nervous system. However, it has not yet been established whether morphological and morphometric parameters differ within corresponding levels of the rat sural nerve. The aims of the present study were to investigate the normal morphological and morphometric aspects of the sural nerve in postnatal developing female rats, with special attention to longitudinal morphology and lateral symmetry. Rats aged 30, 90 and 180 days were killed, and proximal and distal segments of the right and left sural nerves were prepared for light microscopy and morphometric study. No differences were found between the proximal and distal segments or between the right and left sides at the same levels. In addition, postnatal growth continuously and symmetrically affected the sural nerve fascicles and myelinated fibres. Fibre population distribution was also affected by increasing body weight; distribution was unimodal at 30 days, and by 180 days this distribution was established as bimodal. We concluded that the sural nerve is long and constant in its morphology and presents a continuous and symmetrical growth, more pronounced between 30 and 90 days of age, thus providing a good model for experimental neuropathies.
Human IgE response to the Schistosoma haematobium 22·6 kDa antigen
Authors: Fitzsimmons C. M. , Stewart T. J. , Hoffmann Karl F. , Grogan Jane L. , Yazdanbakhsh Maria , Dunne David W.
Published: January 2005

In Schistosoma mansoni and S. japonicum infection, the 22·6 kDa tegumental antigens Sm22·6 and Sj22·6 are principal targets for the human IgE response, and levels of IgE to Sm22·6 have been correlated with resistance to re‐infection after chemotherapy. S. haematobium is arguably a more important species in terms of human infection, and in this report we describe for the first time the molecular characterization of a cDNA from S. haematobium (Sh22·6) that is closely homologous to Sm22·6 and Sj22·6. As a member of the tegument‐associated antigen family, Sh22·6 possesses EF‐hand domains and regions homologous to the dynein light chain domains. We have expressed recombinant Sh22·6 and studied the IgE responses to the antigen in a group of 99 infected individuals (68 children and 31 adults) from an endemic area of Gabon who donated blood before and 5 weeks after praziquantel treatment. IgE to Sh22·6 was detected by ELISA in 18 subjects (18%), and in the majority of responders levels rose between pre‐ and post‐treatment. Interestingly, the proportion of adults expressing IgE to Sh22·6 was 35·5%, significantly higher than the 10·3% seen in children. IgE from at least 10 of the 18 ELISA responders recognized Sh22·6 on Western blots of adult worm extract and recombinant antigen. These results demonstrate that like related molecules in other species, Sh22·6 is a target for the human IgE response. The data also indicate that changes in the IgE response occur with age or with progressive exposure to key antigens.
Assessing quality of life for adolescents in Taiwan
Authors: FUH JONG‐LING , WANG SHUU‐JIUN , LU SHIANG‐RU , JUANG KAI‐DIH
Published: January 2005

Abstract  This study was to evaluate the psychometric properties of the Taiwanese quality of life questionnaire for adolescents and the factors affecting the quality of life of Taiwanese adolescents. The survey involved 5538 junior high school students, aged 13–15 years. An initial 90‐item questionnaire was shortened to 38 items by means of principal component analyses. Quality of life assessment involved seven factors: family, residential environment, personal competence, social relationships, physical appearance, psychological well‐being, and pain. The rate of missing data was low. The Cronbach α coefficient remained above the 0.75 threshold criterion for the global scale and seven subdomain scales. A lower quality of life score was evident for female adolescents in higher grades in school, those living with a single parent or other relatives, and those living in rural areas. This 38‐item questionnaire should serve as a reliable tool for future studies.
Increased risk of relapse after stopping nicotine replacement therapies: a mathematical modelling approach
Authors: Medioni Jacques , Berlin Ivan , Mallet Alain
Published: January 2005

Aims  To describe the effect of nicotine replacement therapy (NRT) on the risk of relapse as a function of time since the quit date.

Data sources  Meta‐analysis of 21 published, randomized, controlled clinical trials, comparing NRT to placebo.

Data extraction  A total of 6644 smokers were treated with NRT and 2766 smokers treated with placebo.

Data synthesis  During treatment with the medication, NRT reduced the hazard ratio (HR) significantly compared with placebo [early HR = 0.62 (95% CI: 0.58–0.67)]. At the end of the average treatment duration (145 days), the HR was 0.81 (95% CI: 0.71–0.94), showing that the benefit was still present at this time. After stopping treatment, the HR increased progressively up to a value of 1.44 (95% CI, 1.18–1.76) showing that the risk of relapse was higher after stopping NRT than after stopping placebo. If NRT and placebo had not been stopped, the HR of smoking relapse would have been established at 0.95 (95% CI: 0.76–1.18, P = 0.64), indicating a similar risk of relapse with NRT and placebo. Moreover, the observed HR of smoking relapse was significantly higher than the expected HR of smoking relapse if NRT had been continued: the difference in HR is 1.51 (95% CI: 1.16–1.98, P < 0.003). This suggests that if NRT had been been continued, around 50% of relapses could have been prevented.

Conclusion  The protective effect of NRT against relapse slowly decreases as a function of time. After stopping NRT, the risk of relapse increases. It may be more beneficial not to stop NRT after the usual 3–6‐month treatment period but to use NRT for longer periods of time.
Do patient characteristics and initial progress in treatment moderate the effectiveness of telephone‐based continuing care for substance use disorders?
Authors: McKay James R. , Lynch Kevin G. , Shepard Donald S. , Morgenstern Jon , Forman Robert F. , Pettinati Helen M.
Published: January 2005

Aims  To determine whether substance use severity, psychiatric severity, social support, self‐help attendance or motivation moderated substance use outcomes in a telephone‐based continuing care intervention.

Design  A randomized study comparing three 12‐week continuing care interventions: weekly telephone monitoring and counseling combined with a support group in the first 4 weeks (TEL), twice‐weekly individualized relapse prevention (RP) and twice‐weekly standard group counseling (STND).

Methods  Following completion of 4‐week intensive out‐patient programs (IOP), 359 patients with alcohol and/or cocaine dependence were assigned randomly to a continuing care condition and followed quarterly for 12 months. Ten potential moderator variables were examined in separate analyses. Two of these variables reflected pretreatment status, whereas the other variables were focused on performance while in the IOP. A composite risk measure was also constructed from dichotomized versions of seven of these variables, with higher scores indicating greater potential for relapse. The dependent measures were total abstinence and percentage of days abstinent from alcohol and cocaine in each quarter.

Findings  Of 40 interaction contrasts that were examined with individual risk indicator measures, only one reached the 0.05 level of significance. Patients with any alcohol use in IOP had a higher percentage of days abstinence in STND than in TEL. In addition, high scores on the composite risk indicator predicted higher total abstinence rates in STND than in TEL, whereas low to moderate scores predicted higher abstinence rates in TEL than in STND.

Conclusion  For most graduates of IOPs, the combination of brief weekly telephone therapeutic contacts and a support group in the first month produced outcomes that are as good as those obtained in more intensive face‐to‐face continuing care interventions. However, patients with current dependence on both alcohol and cocaine who make little progress towards achieving the central goals of IOP may have better outcomes if they receive twice‐weekly group counseling following IOP.
The hTERT‐protein and Ki‐67 labelling index in recurrent and non‐recurrent meningiomas
Authors: Maes L. , Lippens E. , Kalala J. P. O. , De Ridder L.
Published: January 2005

Abstract.  Meningiomas are considered as benign neoplasms affecting the coverings of the central nervous system and compromise approximately 20% of all intracranial tumours. However, a number of these tumours recur even after total resection. The aim of this study is to evaluate the prognostic significance for recurrence of the human telomerase catalytic subunit (hTERT) in the cells of meningiomas. The expression of hTERT‐protein can be evaluated by immunohistochemical staining using a monoclonal antibody against hTERT (clone 44F42, NCL‐L‐hTERT). The interdependence between tumour recurrence and cell proliferation in this study is analysed by Ki‐67 immunoreactivity (clone MIB‐1). Archival material from 29 non‐recurrent and 32 recurrent tumours has been evaluated, including specimens from World Health Organization (WHO) stages I (n = 73), II (n = 2) and III (n = 12). Although the tumours were categorized as benign meningiomas following the WHO classification, recurrence in 22 of 50 cases did not correlate with the tumour stage. For hTERT staining, the following results were found for nucleolar and total nuclear staining, respectively: non‐recurrent meningiomas, 2.9% (± 7.7) and 3.0% (± 8.0); recurrent meningiomas at first resection, 16.8% (± 19.7) and 31.6% (± 30.2). Concerning the Ki‐67 labelling index (LI): for the group of non‐recurrent meningiomas, results were 2.1% (± 1.7) and for the recurrent group at first resection, 1.7% (± 2.0). A significant difference was seen for the hTERT staining (P < 0.001) between the non‐recurrent and recurrent meningiomas, whereas no statistical significance was found for Ki‐67. In conclusion hTERT‐positive meningiomas had a high incidence for recurrence. Ki‐67 was a good marker of cell proliferation status of the tumours, but did not correlate with recurrence; thus, hTERT alone seemed to be a potential predictor for recurrence.
Probing plasmid partition with centromere‐based incompatibility
Authors: Bouet Jean‐Yves , Rech Jérôme , Egloff Sylvain , Biek Donald P. , Lane David
Published: January 2005

Low‐copy number plasmids of bacteria rely on specific centromeres for regular partition into daughter cells. When also present on a second plasmid, the centromere can render the two plasmids incompatible, disrupting partition and causing plasmid loss. We have investigated the basis of incompatibility exerted by the F plasmid centromere, sopC, to probe the mechanism of partition. Measurements of the effects of sopC at various gene dosages on destabilization of mini‐F, on repression of the sopAB operon and on occupancy of mini‐F DNA by the centromere‐binding protein, SopB, revealed that among mechanisms previously proposed, no single one fully explained incompatibility. sopC on multicopy plasmids depleted SopB by titration and by contributing to repression. The resulting SopB deficit is proposed to delay partition complex formation and facilitate pairing between mini‐F and the centromere vector, thereby increasing randomization of segregation. Unexpectedly, sopC on mini‐P1 exerted strong incompatibility if the P1 parABS locus was absent. A mutation preventing the P1 replication initiation protein from pairing (handcuffing) reduced this strong incompatibility to the level expected for random segregation. The results indicate the importance of kinetic considerations and suggest that mini‐F handcuffing promotes pairing of SopB–sopC complexes that can subsequently segregate as intact aggregates.
PMT family of Candida albicans: five protein mannosyltransferase isoforms affect growth, morphogenesis and antifungal resistance
Authors: Prill Stephan K.‐H. , Klinkert Birgit , Timpel Claudia , Gale Cheryl A. , Schröppel Klaus , Ernst Joachim F.
Published: January 2005

Protein O‐mannosyltransferases (Pmt proteins) initiate O‐mannosylation of secretory proteins. The PMT gene family of the human fungal pathogen Candida albicans consists of PMT1 and PMT6, as well as three additional PMT genes encoding Pmt2, Pmt4 and Pmt5 isoforms described here. Both PMT2 alleles could not be deleted and growth of conditional strains, containing PMT2 controlled by the MET3‐ or tetOScHOP1‐promoters, was blocked in non‐permissive conditions, indicating that PMT2 is essential for growth. A homozygous pmt4 mutant was viable, but synthetic lethality of pmt4 was observed in combination with pmt1 mutations. Hyphal morphogenesis of a pmt4 mutant was defective under aerobic induction conditions, yet increased in embedded or hypoxic conditions, suggesting a role of Pmt4p‐mediated O‐glycosylation for environment‐specific morphogenetic signalling. Although a PMT5 transcript was detected, a homozygous pmt5 mutant was phenotypically silent. All other pmt mutants showed variable degrees of supersensitivity to antifungals and to cell wall‐destabilizing agents. Cell wall composition was markedly affected in pmt1 and pmt4 mutants, showing a significant decrease in wall mannoproteins. In a mouse model of haematogenously disseminated infection, PMT4 was required for full virulence of C. albicans. Functional analysis of the first complete PMT gene family in a fungal pathogen indicates that Pmt isoforms have variable and specific roles for in vitro and in vivo growth, morphogenesis and antifungal resistance.
Candida albicans protein kinase CaHsl1p regulates cell elongation and virulence
Authors: Umeyama Takashi , Kaneko Aki , Nagai Yuki , Hanaoka Nozomu , Tanabe Koichi , Takano Yukie , Niimi Masakazu , Uehara Yoshimasa
Published: January 2005

Saccharomyces cerevisiae Hsl1p is a Ser/Thr protein kinase that regulates cell morphology. We identified Candida albicans CaHSL1 and analysed its function in C. albicans. Cells lacking CaHsl1p exhibited filamentous growth under yeast growth conditions with the filaments elongating more quickly than did those of the wild type under hyphal growth conditions, suggesting that it plays a role in the suppression of cell elongation. Green fluorescent protein‐tagged CaHsl1p colocalized with a septin complex to the bud neck during yeast growth or to a potent septation site during hyphal growth, as expected from the localization in S. cerevisiae. However, the localization of the septin complex did not change in ΔCahsl1, suggesting that CaHsl1p does not participate in septin organization. CaHsl1p was expressed in a cell cycle‐dependent manner and, except for the G1 phase, phosphorylated throughout the cell cycle. In ΔCahsl1 cells, the phosphorylation of a possible CaHsl1p target CaSwe1p decreased, while that of CaCdc28p at tyrosine18 increased. Either an extra copy of the tyrosine18‐mutated CaCdc28p or deletion of CaSWE1 suppressed the cell elongation phenotype caused by CaHSL1 deletion. Furthermore, ΔCahsl1 exhibited reduced virulence in the mouse systemic candidiasis model. Thus, the CaHsl1p‐CaSwe1p‐CaCdc28p pathway appears important in the cell elongation of both the yeast and hyphal forms and to the virulence of C. albicans.
Natural merodiploidy involving duplicated rpoB alleles affects secondary metabolism in a producer actinomycete
Authors: Vigliotta Giovanni , Tredici Salvatore Maurizio , Damiano Fabrizio , Montinaro Maria Rosa , Pulimeno Rita , Di Summa Roberta , Massardo Domenica Rita , Gnoni Gabriele V. , Alifano Pietro
Published: January 2005

Actinomadura sp. ATCC 39727 produces the glycopeptide antibiotic A40926, structurally similar to teicoplanin. Production of A40926 is governed by the stringent response at the transcriptional level. In fact, addition of an amino acid pool prevented the transcription of dbv cluster genes involved in the A40926 biosynthesis and the antibiotic production in chemically defined media, and a thiostrepton‐resistant relaxed mutant was severely impaired in its ability to produce the antibiotic. The derivative strain rif19, highly resistant to rifampicin (minimal inhibitory concentration, MIC > 200 µg ml−1), was isolated from the wild type strain that exhibited low resistance to rifampicin (MIC < 25 µg ml−1). In this strain A40926 production started earlier than in the wild type, and reached higher final levels. Moreover, the antibiotic production was not subjected to the stringent control. Molecular analysis led to the identification of two distinct rpoB alleles, rpoBS and rpoBR, in both the wild type and the rif19. rpoBR harboured the H426N missense which is responsible for rifampicin‐resistance in bacteria, in addition to other nucleotide substitutions affecting the primary structure of the RNA polymerase β‐chain. Transcript analysis revealed that rpoBR was expressed at a very low level in the wild type strain during the pseudo‐exponential growth phase, and that the amount of rpoBR mRNA increased during the transition to the stationary phase. In contrast, expression of rpoBR was constitutive in the rif19. The results of mRNA half‐life analysis did not support the hypothesis that post‐transcriptional events are responsible for the different rpoB expression patterns in the two strains, suggesting a role of transcriptional mechanisms.
Role of Mg2+ and pH in the modification of Salmonella lipid A after endocytosis by macrophage tumour cells
Authors: Gibbons Henry S. , Kalb Suzanne R. , Cotter Robert J. , Raetz Christian R. H.
Published: January 2005

Lipid A of Salmonella typhimurium is covalently modified with additional acyl and/or polar substituents in response to activation of the PhoP/PhoQ and/or PmrA/PmrB signalling systems, which are induced by growth at low Mg2+ concentrations and mild acid pH respectively. Although these conditions are thought to exist within macrophage phagolysosomes, no direct evidence for lipid A modification after endocytosis has been presented. To address this issue, we grew S. typhimurium inside RAW264.7 cells in the presence of 32Pi, and then isolated the labelled lipid A fraction, which was found to be extensively derivatized  with phosphoethanolamine, aminoarabinose, 2‐hydroxymyristate and/or palmitate moieties. S. typhimurium grown in tissue culture medium synthesized lipid A molecules lacking all these substituents with the exception of the 2‐hydroxymyristate chain, which was still present. Using defined minimal media to simulate the intracellular pH and Mg2+ concentrations of endosomes, we found that lipid A of S. typhimurium grown in an acidic, low‐Mg2+ medium closely resembled lipid A isolated from bacteria internalized by RAW264.7 cells. A subset of S. typhimurium lipid A modifications were induced by low Mg2+ alone. Escherichia coli K‐12 W3110 modified its lipid A molecules in response to growth under acidic but not low‐Mg2+ conditions. Growth in a high‐Mg2+, mildly alkaline medium resulted in suppression of most lipid A modifications with the exception of the 2‐hydroxymyristate in S. typhimurium. Although lpxO transcription was stimulated by growth on low Mg2+, the biosynthesis of lipid A species containing 2‐hydroxymyristate was independent of PhoP/PhoQ and PmrA/PmrB in S. typhimurium. Our labelling methods should be applicable to studies of lipid A modifications induced by endocytosis of diverse bacteria.
Differential expression of the NRG1 repressor controls species‐specific regulation of chlamydospore development in Candida albicans and Candida dubliniensis
Authors: Staib Peter , Morschhäuser Joachim
Published: January 2005

Candida albicans and Candida dubliniensis are opportunistic fungal pathogens that are closely related but differ in their epidemiology and in some phenotypic characteristics, including certain virulence‐related traits. A comparison of these two species at the molecular level could therefore provide new insights into the biology and pathogenicity of Candida. Both species share the ability to produce chlamydospores, but only C. dubliniensis forms pseudohyphae with abundant chlamydospores on Staib agar (syn. Guizotia abyssinica creatinine agar), on which C. albicans grows as a budding yeast. To understand the basis of this species‐specific, differential regulation of morphogenetic development, we set out to identify C. albicans genes that repress chlamydospore formation under these conditions. A C. albicans genomic library was integrated into the C. dubliniensis genome and transformants were screened for clones in which filamentation and/or chlamydospore production on Staib agar was suppressed. This screen identified two genes, CaNRG1 and CaPDE2, encoding a general transcriptional repressor and a high affinity cAMP phosphodiesterase, respectively. Expression of CaNRG1 in C. dubliniensis repressed pseudohyphae and chlamydospore formation, whereas expression of CaPDE2 only reduced the extent of filamentous growth but did not affect chlamydospore formation. We found that C. dubliniensis, but not C. albicans, specifically downregulates NRG1 expression on Staib medium to allow chlamydospore development. Artificial overexpression of CdNRG1 suppressed pseudohyphal growth and production of chlamydospores in C. dubliniensis. Conversely, deletion of CaNRG1 in C. albicans resulted in chlamydospore formation on Staib agar, confirming its central role in the regulation of this morphogenetic process. Our results demonstrate that differential regulation of a single gene, NRG1, in C. albicans and C. dubliniensis is responsible for their species‐specific response to environmental signals that induce chlamydospore development.
Ca2+‐dependent expression of the CIRCE regulon inStreptococcus pneumoniae
Authors: Kwon Hyog‐Young , Kim Su‐Nam , Pyo Suhk‐Neung , Rhee Dong‐Kwon
Published: January 2005

DnaK and GroEL play a pivotal role in protein folding, and promote cell proliferation and survival. In Gram‐positive and several Gram‐negative bacteria, HrcA represses the transcription ofdnaKandgroEoperons by binding to the highly conserved CIRCE (controllinginvertedrepeat ofchaperoneexpression) operator sequence in the presence of GroEL. HrcA may respond to environmental stress and various other factors that modulate the transcription of thednaKandgroEoperons. However, the mechanisms by which these factors modulate the activity of HrcA remain elusive. Here, we show that the thermoresistance ofStreptococcus pneumoniaeis significantly repressed in the presence of Ca2+. Furthermore, heat shock‐induced expression of the CIRCE regulon inS. pneumoniaeis repressed in the presence of Ca2+, although to a lesser degree than in thehrcAmutant, strongly suggesting that HrcA inhibits expression of the CIRCE regulon in a Ca2+‐dependent manner. Although HrcA does not bind directly to Ca2+, its hydrophobicity is increased in the presence of the metal ion. Taken together, our observations suggest that Ca2+induces conformational changes, such as exposure of the hydrophobic surfaces of HrcA, which facilitate binding to GroEL. Alternatively, the presence of Ca2+may facilitate GroEL in interacting freely with HrcA. This, in turn, enhances access to CIRCE and leads to repression of thednaKandgroEoperons inS. pneumoniae.
Identification of novel non‐coding RNAs as potential antisense regulators in the archaeon Sulfolobus solfataricus
Authors: Tang Thean‐Hock , Polacek Norbert , Zywicki Marek , Huber Harald , Brugger Kim , Garrett Roger , Bachellerie Jean Pierre , Hüttenhofer Alexander
Published: January 2005

By generating a specialized cDNA library from the archaeon Sulfolobus solfataricus, we have identified 57 novel small non‐coding RNA (ncRNA) candidates and confirmed their expression by Northern blot analysis. The majority was found to belong to one of two classes, either antisense or antisense‐box RNAs, where the latter only exhibit partial complementarity to RNA targets. The most prominent group of antisense RNAs is transcribed in the opposite orientation to the transposase genes, encoded by insertion elements (transposons). Thus, these antisense RNAs may regulate transposition of insertion elements by inhibiting expression of the transposase mRNA. Surprisingly, the class of antisense RNAs also contained RNAs complementary to tRNAs or sRNAs (small‐nucleolar‐like RNAs). For the antisense‐box ncRNAs, the majority could be assigned to the class of C/D sRNAs, which specify 2′‐O‐methylation sites on rRNAs or tRNAs. Five C/D sRNAs of this group are predicted to target methylation at six sites in 13 different tRNAs, thus pointing to the widespread role of these sRNA species in tRNA modification in Archaea. Another group of antisense‐box RNAs, lacking typical C/D sRNA motifs, was predicted to target the 3′‐untranslated regions of certain mRNAs. Furthermore, one of the ncRNAs that does not show antisense elements is transcribed from a repeat unit of a cluster of small regularly spaced repeats in S. solfataricus which is potentially involved in replicon partitioning. In conclusion, this is the first report of stably expressed antisense RNAs in an archaeal species and it raises the prospect that antisense‐based mechanisms are also used widely in Archaea to regulate gene expression.
The potential impact of genetic counseling for mental illness
Authors: Austin JC , Honer WG
Published: January 2005

Mental disorders are relatively highly heritable, yet complex with important interactions between genetic risk and environmental factors in determining illness expression. Due to the high prevalence of these complex disorders, steady increase in knowledge about genetic contributions, and increasing public awareness, this area may come to represent a significant proportion of all genetic counseling. The potential impact of genetic counseling in mental illness is broad. As well as the conventional expectations, genetic counseling may have the positive outcomes of reducing the guilt, shame, and stigma associated with mental illness, even within families. However, like many interventions in medicine, genetic counseling for mental disorders could potentially have unintended consequences resulting in increased stigma, guilt, and shame. The potential impacts of genetic education and providing recurrence risks on stigma are reviewed, as well as the role of education about the environment as a way of modifying family members' guilt. The review allows a preliminary formulation of a series of suggestions for genetic counseling in mental illness.
A novel microdeletion syndrome with loss of the MSH2 locus and hereditary non‐polyposis colorectal cancer
Authors: Lucci‐Cordisco E , Zollino M , Baglioni S , Mancuso I , Lecce R , Gurrieri F , Crucitti A , Papi L , Neri G , Genuardi M
Published: January 2005

Constitutional chromosome deletions can predispose to the development of cancer with the phenotypic characteristics of inherited cancer syndromes, when the deleted region encompasses a tumour suppressor gene. Examples of such conditions are represented by the cytogenetic deletions associated with retinoblastoma, Wilms tumour and familial adenomatous polyposis. So far, no constitutional deletions involving the genes implicated in hereditary non‐polyposis colorectal cancer (HNPCC) have been identified. This may be at least partially because of the lack of distinctive phenotypic manifestations in HNPCC. We describe the first case of a constitutional microdeletion associated with HNPCC. Suspicion of a microdeletion was prompted by the association of mental retardation, postnatal growth deficiency, minor congenital anomalies and early onset (37 years) sporadic colon cancer. The patient was found to harbour a microdeletion within chromosome 2p16‐p21, including the MSH2 gene. Since there are very few reports of deletions of the 2p16‐p21 region, our observation sets the grounds for the definition of a novel multiple congenital anomaly/mental retardation/cancer microdeletion syndrome.
A family exhibiting arterial tortuosity syndrome displays homozygosity for markers in the arterial tortuosity locus at chromosome 20q13
Authors: Zaidi SHE , Peltekova V , Meyer S , Lindinger A , Paterson AD , Tsui L‐C , Faiyaz‐Ul‐Haque M , Teebi AS
Published: January 2005

Arterial tortuosity associated with hyperextensible skin and hypermobility of joints, features that are characteristics of Ehlers–Danlos syndrome (EDS), has been described in several families. An arterial tortuosity locus has recently been mapped to chromosome 20q13. Here, we report a consanguineous Kurdish family in which an affected child manifested elongation and severe tortuosity of the aorta, carotid, and other arteries. Additional clinical symptoms include loose skin, hypermobile joints, hernias, and facial features that resemble EDS individuals. To examine whether the arterial tortuosity locus was involved in this child, homozygosity analysis was performed using microsatellite markers on 20q13. The affected child was found homozygous, whereas the unaffected parents and three siblings were heterozygous. Additional typing defined the genomic interval to a 37‐cm region within which the arterial tortuosity locus is located. Three functional candidate genes (B4GALT5, KCNB1, and PTGIS) were sequenced. No mutations were discovered in the coding regions of these three genes and the promoter regions of B4GALT5 and KCNB1 genes. Moreover, the B4GALT5 mRNA expression was unaltered in patient‐derived lymphoblastoid cells. In the PTGIS gene promoter, the affected child was homozygous for eight variable number of tandem repeats, while parents and unaffected siblings carried six repeats.
Pseudomembranous colitis in children
Authors: BROOK ITZHAK
Published: January 2005

This review presents the microbiology, management and prevention of pseudomembranous colitis (PMC) in children. PMC is commonly associated with prior antibiotic exposure and hospitalization. It is caused almost exclusively by toxins produced by Clostridium difficile. The clinical spectrum of this disease may range from a mild, non‐specific diarrhea to severe colitis with toxic megacolon, perforation, and death. PMC may affect all age groups, although a lower incidence has been noted in children. Ampicillin, amoxicillin, the second‐ and third‐generation cephalosporins and clindamycin are the drugs most frequently associated with development of PMC, although nearly all antimicrobials have been implicated as causes of diarrhea and colitis. Discontinuation of antibiotics and supportive therapy usually lead to resolution of this disorder. Administration of oral vancomycin or other therapeutic regimens may be needed.
Changes in serum lipid concentrations in patients with chronic hepatitis C virus positive hepatitis responsive or non‐responsive to interferon therapy
Authors: HAMAMOTO SACHIKO , UCHIDA YASUSHI , WADA TOMOKO , MORITANI MAKOTO , SATO SHUICHI , HAMAMOTO NAOHARU , ISHIHARA SHUNJI , WATANABE MAKOTO , KINOSHITA YOSHIKAZU
Published: January 2005

Background: Changes in serum lipid concentrations during the administration of interferon to patients with chronic hepatitis C virus (HCV) infection have not been fully investigated. The present study was designed to compare changes in serum lipid concentrations before, during and after interferon therapy in responders and non‐responders to treatment.

Methods: In total, 101 patients with chronic HCV positive hepatitis were enrolled in this study. High dose interferon alpha was given on alternate days for 6 months. Six months after the end of treatment patients were assessed for the presence or absence of HCV RNA to determine the results of interferon treatment. The time courses of changes in serum lipid concentrations were measured in all patients.

Results: The total cholesterol level increased gradually during and after interferon therapy, and its pattern of change coincided with that of serum cholinesterase activity. Pretreatment serum cholesterol concentrations did not differ between responders and non‐responders to interferon therapy. The serum triglyceride concentration, conversely, showed a sharp increase during interferon administration and returned to its basal level after the end of treatment. Responders to interferon therapy tended to have higher pretreatment triglyceride concentrations than did non‐responders.

Conclusions: We clarified that serum cholesterol and triglyceride levels showed different patterns of change during interferon therapy.
Comparative study of nizatidine and famotidine for maintenance therapy of erosive esophagitis
Authors: HAMAMOTO NAOHARU , HASHIMOTO TOMOYUKI , ADACHI KYOICHI , HIRAKAWA KAZUYA , ISHIHARA SHUNJI , INOUE HARUE , TANIURA HIROYUKI , NIIGAKI MASATOSHI , SATO SHUICHI , KUSHIYAMA YOSHINORI , SUETSUGU HIROSHI , MIYAKE TATSUYA , KINOSHITA YOSHIKAZU
Published: January 2005

Background: The therapeutic effect of combined administration of prokinetics and histamine H2 receptor antagonists (H2RA) in gastroesophageal reflux disease is reported to be superior to that of monotherapy with H2RA alone. In addition to its acid‐suppressing effect, the H2RA nizatidine also has a prokinetic action by suppressing acetylcholine esterase. The present multicenter, randomized controlled study was performed to investigate whether nizatidine is superior to famotidine, which does not suppress acetylcholine esterase activity, in maintenance therapy for erosive esophagitis. In addition, the question as to whether the grade of erosive esophagitis affects the non‐recurrence rate during the maintenance therapy with H2RA was also investigated.

Methods: Seventy‐two patients with endoscopically healed erosive esophagitis after 8 weeks of initial treatment with proton pump inhibitors were randomly divided into two groups. Patients in the nizatidine group were treated with 150 mg nizatidine twice a day (b.i.d.), while patients in the famotidine group were treated with 20 mg famotidine b.i.d. for 6 months. At the end of therapy, and at the time when patients complained of symptoms, endoscopic investigations were repeated to find out whether the esophagitis had recurred.

Results: Nizatidine produced a significantly higher non‐recurrence rate than famotidine (P = 0.049 in intention‐to‐treat [ITT] analysis). This difference of remission rate between nizatidine and famotidine was observed mainly in grade B esophagitis (P = 0.016 in ITT analysis).

Conclusion: Nizatidine is a more effective H2RA than famotidine in the maintenance therapy of patients with reflux esophagitis.