bluuebunny/crossref_metadata_2025 huggingface dataset:
Testing standard and genetic parameters in 220 patients with multiple myeloma with complete data sets: superiority of molecular genetics
Authors: Shaughnessy John D. , Haessler Jeffrey , Van Rhee Frits , Anaissie Elias , Pineda‐Roman Mauricio , Cottler‐Fox Michele , Hollmig Klaus , Zangari Maurizio , Mohiuddin Abid , Alsayed Yazan , Grazziutti Monica , Epstein Joshua , Crowley John , Barlogie Bart
Published: May 2007

Prognostic models for multiple myeloma have been fraught with tremendous heterogeneity in outcome among subgroups. In the context of Total Therapy 2, a tandem transplant trial for newly diagnosed myeloma, comprehensive information was available in 220 patients on standard prognostic factors (SPF), magnetic resonance imaging (MRI)‐defined focal lesions, cytogenetic abnormalities (CA), fluorescence‐in‐situ‐hybridisation (FISH)‐derived amplification of chromosome 1q21 (amp1q21) and deletion of 13q14, as well as gene expression profiling (GEP). Five multivariate analysis‐based survival models were derived, utilising SPF only (model 1), with progressive addition of CA (model 2), MRI (model 3), FISH (model 4) and GEP (model 5). TheR2value, a measure of accounting for clinical outcome variability, increased progressively from 18% in model 1 to 38% in model 5. The hazard ratio for overall survival was highest for GEP (3·07,P < 0·001) followed by amp1q21 (1·71,P = 0·05). According to the presence of none (49%), one (35%) or both of these two risk features (16%), 3‐year survival decreased progressively from 92% to 78% to 43% (P < 0·0001). Thus, the dominance over other prognostic parameters of molecular genetics justifies the generation of quantitative reverse transcription polymerase chain reaction methodology (‘MM genetic kit’) for the optimal risk stratification of patients participating in therapeutic trials.
Shell decay rates of native and alien freshwater bivalves and implications for habitat engineering
Authors: STRAYER DAVID L. , MALCOM HEATHER M.
Published: May 2007

1. Spent shells of bivalves can provide habitat for other organisms, as well as playing important roles in biogeochemical cycles. The amount of spent shell material that will accumulate at a site depends on rates of both shell production and decay, although the latter is rarely considered.

2. We measured the instantaneous decay rates of four species of freshwater bivalves across a range of sites in south‐eastern New York, and found that rates varied by more than 500‐fold across sites and species.

3. Differences in decay rates were related to water chemistry (Ca, pH, dissolved inorganic C), the presence of a current, and the size of the bivalve shell.

4. Combining these decay rates with estimates of shell production derived from the literature, we conclude that the Unionidae, Corbicula, and Dreissena are all capable of producing large accumulations (>10 kg dry mass m−2) of spent shells, while members of the Sphaeriidae probably rarely will produce such large accumulations.

5. Hence the replacement of native unionid bivalves by the alien Corbicula and Dreissena may have little effect on standing stocks of spent shells, unless the aliens invade sites where unionids are scarce or absent.
Automatic differentiation in geophysical inverse problems
Authors: Sambridge M. , Rickwood P. , Rawlinson N. , Sommacal S.
Published: May 2007

Automatic differentiation (AD) is the technique whereby output variables of a computer code evaluating any complicated function (e.g. the solution to a differential equation) can be differentiated with respect to the input variables. Often AD tools take the form of source to source translators and produce computer code without the need for deriving and hand coding of explicit mathematical formulae by the user. The power of AD lies in the fact that it combines the generality of finite difference techniques and the accuracy and efficiency of analytical derivatives, while at the same time eliminating ‘human’ coding errors. It also provides the possibility of accurate, efficient derivative calculation from complex ‘forward’ codes where no analytical derivatives are possible and finite difference techniques are too cumbersome. AD is already having a major impact in areas such as optimization, meteorology and oceanography. Similarly it has considerable potential for use in non-linear inverse problems in geophysics where linearization is desirable, or for sensitivity analysis of large numerical simulation codes, for example, wave propagation and geodynamic modelling. At present, however, AD tools appear to be little used in the geosciences. Here we report on experiments using a state of the art AD tool to perform source to source code translation in a range of geoscience problems. These include calculating derivatives for Gibbs free energy minimization, seismic receiver function inversion, and seismic ray tracing. Issues of accuracy and efficiency are discussed.
Long‐term major joint outcomes in young adults with haemophilia: interim data from the HGDS
Authors: SU Y. , WONG W.‐Y. , LAIL A. , DONFIELD S. M. , KONZAL S. , GOMPERTS E. ,   THE HEMOPHILIA GROWTH AND DEVELOPMENT STUDY
Published: May 2007

Summary.  A study of major joint outcomes, specifically range of motion and synovitis, was conducted with data from a subset of adolescents enrolled in the prospective Hemophilia Growth and Development Study (HGDS). Clinical observations were carried out over a 7‐year period from 1989 to 1996. A secondary aim was to gain insight into factors that might influence decisions regarding maintaining or discontinuing prophylaxis during early adulthood. Twenty‐nine participants (median age 17.4 at entry) were included. Median follow‐up was 7 years (range: 4.8–7.7). Range of motion (ROM) and synovitis in six major joints (knees, elbows and ankles), were evaluated by physical examination every 6–12 months. At the baseline observation, 73.6% of joints showed no ROM abnormalities or synovitis, and all joints were normal in 11 patients. Of the 11 participants, 54.5% developed abnormalities and 28.1% of normal joints at baseline became abnormal during the follow‐up. Ankles were the most severely affected and had persistent progression during late adolescence and adulthood. Elbows and knees did not show progression after the first few years of the follow‐up. The progression of haemophilic arthropathy in adolescents and young adults varies from individual to individual and also in the site of affected joints. In view of this, the decision regarding discontinuation of prophylaxis in patients with haemophilia should be individualized.
Analysis of Factor VIII polymorphic markers as a means for carrier detection in Brazilian families with haemophilia A
Authors: DE CARVALHO F. M. , DE VARGAS WOLFGRAMM E. , PANETO G. G. , DE PAULA CARETA F. , SPAGNOL PERRONE A. M. , DE PAULA F. , LOURO I. D.
Published: May 2007

Summary.  Haemophilia A is an X‐linked, recessively inherited bleeding disorder of varying severity, which results from the deficiency of procoagulant factor VIII f(8). Linkage diagnosis using polymorphic markers in the f8 gene is widely used to detect carriers. The objective of this study was to verify the informativeness of three polymorphic markers in the Brazilian population, to evaluate the usefulness of such markers in carrier detection procedures. Sixty‐three unrelated healthy volunteers and 10 haemophilic families were studied. Two microsatellite repeats and one HindIII RFLP markers were used. Carrier and non‐carrier status could be determined in 80% of females investigated. Intron 13 markers presented the highest heterozygosity rate (79%) followed by intron 22 (68%) and intron 19 (57%). When all three markers were used together, linkage analysis informativeness increased significantly. We conclude that these markers are suitable for carrier detection in the Brazilian population and we recommend their use in combination to maximize diagnostic efficiency.
Glycogen synthase kinase 3 activity during development of bone marrow‐derived dendritic cells (DCs) essential for the DC function to induce T helper 2 polarization
Authors: Ono Takenori , Yanagawa Yoshiki , Iwabuchi Kazuya , Nonomura Katsuya , Onoé Kazunori
Published: May 2007

Dendritic cells (DCs) polarize naive CD4+ T cells to either T helper 1 (Th1) or Th2 cells. We examined the role of glycogen synthase kinase 3 (GSK3) activity during DC development from murine bone marrow (BM) cells. DCs were generated by culturing lineage‐marker‐negative BM cells with granulocyte–macrophage colony‐stimulating factor in the presence or absence of a specific inhibitor of GSK3 (Gi), SB415286, for 6 days. DCs generated in the presence (GiDC) or absence (control DC) of SB415286 similarly exhibited a conventional DC phenotype (CD11b+ B220– CD8–). These DCs were mixed with allogeneic CD4+ T cells and the ability to polarize Th1 or Th2 cells was evaluated. The GiDCs exhibited markedly impaired function to induce Th2 polarization compared to control DCs. In contrast, the ability of GiDCs to generate Th1 cells was slightly higher than that of control DCs. CD86 expression and CD40‐mediated interleukin‐6 production were completely diminished in GiDCs, which might be associated with the impaired ability of the GiDCs to induce Th2 differentiation. These results suggest that the GSK3 activity during DC development is essential for the establishment of the DC function to induce Th2, but not Th1, differentiation.
Aberrant T‐cell ontogeny and defective thymocyte and colonic T‐cell chemotactic migration in colitis‐prone Gαi2‐deficient mice
Authors: Elgbratt Kristina , Bjursten Malin , Willén Roger , Bland Paul W. , Hörnquist Elisabeth Hultgren
Published: May 2007

Gαi2‐deficient mice, which spontaneously develop colitis, have previously been reported to have an increased frequency of mature, single positive thymocytes compared to wild‐type mice. In this study we further characterized the intrathymic changes in these mice before and during overt colitis. Even before the onset of colitis, Gαi2–/– thymi weighed less and contained fewer thymocytes, and this was exacerbated with colitis development. Whereas precolitic Gαi2–/– mice had unchanged thymocyte density compared to Gαi2+/– mice of the same age, this was significantly decreased in mice with colitis. Thymic atrophy in Gαi2–/– mice involved mainly the cortex. Using a five‐stage phenotypic characterization of thymocyte maturation based on expression of CD4, CD8, TCRαβ, CD69 and CD62L, we found that both precolitic and colitic Gαi2–/– mice had significantly increased frequencies of mature single‐positive CD4+ and CD8+ medullary thymocytes, and significantly reduced frequencies and total numbers of immature CD4+ CD8+ double‐positive thymocytes compared to Gαi2+/– mice. Furthermore, cortical and transitional precolitic Gαi2–/– thymocytes showed significantly reduced chemotactic migration towards CXCL12, and a trend towards reduced migration to CCL25, compared to wild‐type thymocytes, a feature even more pronounced in colitic mice. This impaired chemotactic migration of Gαi2–/– thymocytes could not be reversed by increased chemokine concentrations. Gαi2–/– thymocytes also showed reduced expression of the CCL25 receptor CCR9, but not CXCR4, the receptor, for CXCL12. Finally, wild‐type colonic lamina propria lymphocytes migrated in response to CXCL12, but not CCL25 and, as with thymocytes, the chemokine responsiveness was significantly reduced in Gαi2–/– mucosal lymphocytes.
Instruction of naive CD4+ T‐cell fate to T‐bet expression and T helper 1 development: roles of T‐cell receptor‐mediated signals
Authors: Ariga Haruyuki , Shimohakamada Yoko , Nakada Makiyo , Tokunaga Takeshi , Kikuchi Takeshi , Kariyone Ai , Tamura Toshiki , Takatsu Kiyoshi
Published: May 2007

Using T‐cell receptor (TCR) transgenic mice, we demonstrate that TCR stimulation of naive CD4+ T cells induces transient T‐bet expression, interleukin (IL)‐12 receptor β2 up‐regulation, and GATA‐3 down‐regulation, which leads to T helper (Th)1 differentiation even when the cells are stimulated with peptide‐loaded I‐Ab‐transfected Chinese hamster ovary cells in the absence of interferon‐γ (IFN‐γ) and IL‐12. Sustained IFN‐γ and IL‐12 stimulation augments naive T‐cell differentiation into Th1 cells. Intriguingly, a significant Th1 response is observed even when T‐bet–/– naive CD4+ T cells are stimulated through TCR in the absence of IFN‐γ or IL‐12. Stimulation of naive CD4+ T cells in the absence of IFN‐γ or IL‐12 with altered peptide ligand, whose avidity to the TCR is lower than that of original peptide, fails to up‐regulate transient T‐bet expression, sustains GATA‐3 expression, and induces differentiation into Th2 cells. These results support the notion that direct interaction between TCR and peptide‐loaded antigen‐presenting cells, even in the absence of T‐bet expression and costimulatory signals, primarily determine the fate of naive CD4+ T cells to Th1 cells.
Salmonella‐induced SipB‐independent cell death requires Toll‐like receptor‐4 signalling via the adapter proteins Tram and Trif
Authors: Cook Pamela , Tötemeyer Sabine , Stevenson Catherine , Fitzgerald Katherine A. , Yamamoto Masahiro , Akira Shizuo , Maskell Duncan J. , Bryant Clare E.
Published: May 2007

Salmonella enterica serovar typhimurium (S. typhimurium) is an intracellular pathogen that causes macrophage cell death by at least two different mechanisms. Rapid cell death is dependent on the Salmonella pathogenicity island‐1 protein SipB whereas delayed cell death is independent of SipB and occurs 18–24 hr post infection. Lipopolysaccharide (LPS) is essential for the delayed cell death. LPS is the main structural component of the outer membrane of Gram‐negative bacteria and is recognized by Toll‐like receptor 4, signalling via the adapter proteins Mal, MyD88, Tram and Trif. Here we show that S. typhimurium induces SipB‐independent cell death through Toll‐like receptor 4 signalling via the adapter proteins Tram and Trif. In contrast to wild type bone marrow derived macrophages (BMDM), Tram–/– and Trif–/– BMDM proliferate in response to Salmonella infection.
Corticosterone impairs dendritic cell maturation and function
Authors: Elftman Michael D. , Norbury Christopher C. , Bonneau Robert H. , Truckenmiller Mary E.
Published: May 2007

Dendritic cells (DC) play a critical role in initiating and directing adaptive immune responses against pathogens and tumours. Immature DC are thought to act as sentinels in peripheral tissues where their main function is to capture antigen at sites of infection, whereas mature DC are highly efficient at priming T‐cell‐mediated immune responses against infectious pathogens. The DC maturation process is thought to be an important step in the efficient generation of cytotoxic T lymphocytes (CTL). It is well established that many aspects of immune function, including CTL‐mediated antiviral immunity, are modulated by neuroendocrine‐derived products. Corticosterone (CORT), an adrenal hormone produced at increased concentrations during a stress response, has been shown to play a role in impaired CTL responses in stressed animals, leading to high mortality in mice normally resistant to viral infection. While direct effects of neuroendocrine mediators on CTL have been studied, little is known about their effects on DC that are critical for CTL priming. Here, we found that physiologically relevant concentrations of CORT, acting via the glucocorticoid receptor, functionally compromise DC maturation. DC exposed to CORT remained phenotypically and functionally immature after stimulation with lipopolysaccharide and were impaired for the production of interleukin (IL)‐6, IL‐12, and tumour necrosis factor‐α. These effects were biologically significant, as CORT treatment resulted in a marked reduction in the ability of DC to prime naive CD8+ T cells in vivo. These findings offer a potential mechanism underlying stress‐associated immunosuppression.
Rates of mass gain and energy deposition in red knot on their final spring staging site is both time‐ and condition‐dependent
Authors: ATKINSON PHILIP W. , BAKER ALLAN J. , BENNETT KAREN A. , CLARK NIGEL A. , CLARK JACQUIE A. , COLE KIMBERLY B. , DEKINGA ANNE , DEY AMANDA , GILLINGS SIMON , GONZÁLEZ PATRICIA M. , KALASZ KEVIN , MINTON CLIVE D. T. , NEWTON JASON , NILES LAWRENCE J. , PIERSMA THEUNIS , ROBINSON ROBERT A. , SITTERS HUMPHREY P.
Published: May 2007

Millions of shorebirds migrate each year through a small number of highly productive staging areas where they often conflict with fisheries interests. Delaware Bay, USA, is a major shorebird stopover site where, in spring, many thousands of shorebirds undergo rapid mass gain by feeding on the eggs of commercially harvested horseshoe crabs Limulus polyphemus.

Environmental factors may cause deviations from the best migration schedule. We used within‐year mass gain data from red knot Calidris canutus caught in Delaware Bay between 1998 and 2005 to determine the degree of flexibility individuals have to vary migration speed.

Mass gain by birds below 133 g was shown to comprise 15·3% fat (39 kJ g−1), the remainder being lean mass (6 kJ g−1). Above this critical level, fat comprised 83·9% of mass deposition. The rates of energy deposition (kJ d−1) were therefore fundamentally different between the two states but were among the highest ever recorded among vertebrates (5–7 × basic metabolic rate).

A total of 36–62% of the variation in observed rates of energy deposition between 1998 and 2002 was explained by a year factor, date and mass at initial capture and interaction terms, such that light‐weight birds at the end of May had rates of mass gain or energy deposition two to three times higher than birds of similar mass in mid‐May, indicating that birds were attempting to achieve a certain mass by a certain date. In 2003 and 2005, this relationship broke down as a result of lower densities of eggs.

Synthesis and application. The maintenance of high densities of crab eggs required for high rates of mass gain in red knot requires severe cuts in, or the complete cessation of, the crab harvest, reduced human and raptor‐related disturbance as well as management of beaches to provide sufficient crab‐spawning habitat. These findings are widely applicable to other systems where harvesting activities come into conflict with migrating animals and show that certain sections of the population, in this case the long‐distance migrants from South America, will be impacted more than short‐distance migrants whose physiology may give them access to alternative food resources.
Reconsidering simulations in science education at a distance: features of effective use
Authors: Blake C. , Scanlon E.
Published: May 2007

Abstract  This paper proposes a reconsideration of use of computer simulations in science education. We discuss three studies of the use of science simulations for undergraduate distance learning students. The first one, The Driven Pendulum simulation is a computer‐based experiment on the behaviour of a pendulum. The second simulation, Evolve is concerned with natural selection in a hypothetical species of a flowering plant. The third simulation, The Double Slit Experiment deals with electron diffraction and students are provided with an experimental setup to investigate electron diffraction for double and single slit arrangements. We evaluated each simulation, with 30 students each for The Driven Pendulum and Evolve simulations and about 100 students for The Double Slit Experiment. From these evaluations we have developed a set of the features for the effective use of simulations in distance learning. The features include student support, multiple representations and tailorability.
Analysing the use of interactive technology to implement interactive teaching
Authors: Kennewell S. , Tanner H. , Jones S. , Beauchamp G.
Published: May 2007

Abstract  Recent policy initiatives in England have focused on promoting ‘interactive’ teaching in schools, with a clear expectation that this will lead to improvements in learning. This expectation is based on the perceived success of such approaches in other parts of the world. At the same time, there has been a large investment in Information and Communication Technology (ICT) resources, and particularly in interactive whiteboard technology. This paper explores the idea of interactive teaching in relation to the interactive technology which might be used to support it. It explains the development of a framework for the detailed analysis of teaching and learning in activity settings which is designed to represent the features and relationships involved in interactivity. When applied to a case study of interactive teaching during a lesson involving a variety of technology‐based activities, the framework reveals a confusion of purpose in students' use of an ICT resource that limits the potential for learning when students are working independently. Discussion of relationships between technical and pedagogical interactivity points a way forward concerning greater focus on learning goals during activity in order to enable learners to be more autonomous in exploiting ICT's affordances, and the conclusion identifies the variables and issues which need to be considered in future research which will illuminate this path.
Susceptibility of salmonid alphavirus to a range of chemical disinfectants
Authors: Graham D A , Cherry K , Wilson C J , Rowley H M
Published: May 2007

A range of commercially available disinfectants were tested for efficacy against salmonid alphavirus under a range of different conditions including variations in concentration, temperature, contact time, water type and presence or absence of organic matter. Testing was based on the protocol defined in the draft European Standard prEN 14675, for which the effective standard is a 4 log(10) reduction in viral titre. All disinfectants were found to be effective under at least some of the conditions tested. However, the presence of organic matter in particular was shown to be detrimental in some cases, either through rendering some disinfectants ineffective, or by production of a visible inhomogeneity.
Yersinia ruckeri infections in salmonid fish
Authors: Tobback E , Decostere A , Hermans K , Haesebrouck F , Chiers K
Published: May 2007

Yersinia ruckeri is the causative agent of yersiniosis or enteric redmouth disease leading to significant economic losses in salmonid aquaculture worldwide. Infection may result in a septicaemic condition with haemorrhages on the body surface and in the internal organs. Despite the significance of the disease, very little information is available on the pathogenesis, hampering the development of preventive measures to efficiently combat this bacterial agent. This review discusses the agent and the disease it causes. The possibility of the presence of similar virulence markers and/or pathogenic mechanisms between the Yersinia species which elicit disease in humans and Y. ruckeri is also examined.
Self‐determination, social abilities and the quality of life of people with intellectual disability
Authors: Nota L. , Ferrari L. , Soresi S. , Wehmeyer M.
Published: May 2007

Background  The international literature has documented that self‐determination is impacted by environmental factors, including living or work settings; and by intraindividual factors, including intelligence level, age, gender, social skills and adaptive behaviour. In addition, self‐determination has been correlated with improved quality of life (QoL). This study sought to contribute to the growing literature base in this area by examining the relationship among and between personal characteristics, self‐determination, social abilities and the environmental living situations of people with intellectual disabilities (ID).

Methods  The study involved 141 people with ID residing in Italy. Healthcare professionals and social workers who had known participants for at least 1 year completed measures of self‐determination, QoL and social skills. Analysis of variance was conducted to verify whether different levels of intellectual impairment were associated with different degrees of the dependent variables. The Pearson product–moment correlation was used to examine any relationships among dependent variables and IQ scores. Finally, discriminant function analysis was used to examine the degree to which IQ score, age, self‐determination and social abilities predicted membership in groups that were formed based on living arrangement, and on QoL status (high vs. low).

Results  The anova determined, as expected, that participants with more severe ID showed the lowest levels of self‐determination, QoL and social abilities. Discriminant function analysis showed that (a) individuals attending day centres were distinguished from those living in institutions in that they were younger and showed greater autonomy of choice and self‐determination in their daily activities; (b) basic social skills and IQ score predicted membership in the high or low QoL groups; and (c) the IQ score predicted membership in the high or low self‐determination groups. A manova conducted to examine gender‐ and age‐level differences on self‐determination found gender differences; women had higher self‐determination scores than men.

Conclusions  These findings contribute to an emerging knowledge base pertaining to the role of intraindividual and environmental factors in self‐determination and QoL. In general, the study replicated findings pertaining to the relative contribution of intelligence to self‐determination and QoL, added information about the potential contribution of social abilities, and pointed to the potentially important role of opportunities to make choices as a particularly important aspect of becoming more self‐determined, at least in the context of residential settings.
Predictors of depressive symptoms in primary caregivers of young children with or at risk for developmental delay
Authors: Feldman M. , McDonald L. , Serbin L. , Stack D. , Secco M. L. , Yu C. T.
Published: May 2007

Background  Despite extensive research with families raising children with or at risk for developmental delay (DD), it is not clear whether primary caregivers of these children are at increased risk for depressive symptoms. Discrepant findings in the literature may be owing to heterogeneity of child problems. More research is needed on child, parent and family variables that may increase risk for, or resilience to, caregiver depressive symptoms. Some studies have found that parental resources (e.g. social support and coping strategies) may buffer the effects of parental distress, while other studies have highlighted the role of parental self‐efficacy.

Methods  We examined Beck Depression Inventory (BDI) scores in 178 primary caregivers (mainly biological mothers) who had 2‐year‐old children with or at risk for DD owing to: (a) low birthweight, prematurity or multiple birth (n = 58), (b) other known reasons (e.g. Down syndrome, spina bifida) (n = 67), or (c) unknown reasons (n = 69).

Results  We found that 20% (n = 35) of the caregivers scored above the BDI clinical cut‐off for depression. Analysis of variance revealed that caregivers with elevated BDI scores had higher child behaviour problem and escape‐avoidance coping scores, and lower social support and parent self‐efficacy, compared with caregivers without depressive symptoms. Caregivers with children who had DD for unknown reasons had higher BDI scores than caregivers of the other two groups of children. Regression analyses showed that child behaviour problems, escape‐avoidance coping strategies and social support predicted caregiver BDI scores, but caregiver self‐efficacy only did so when entered independently of social support. Only social support mediated and (marginally) moderated the relationship between child behaviour problems and caregiver depressive symptoms.

Conclusions  These findings suggest that early intervention programmes should carefully consider the interaction of child characteristics (e.g. Diagnosis and behaviour problems), caregiver resources (e.g. coping strategies and social support), and parental mental health and mood when planning and tailoring services for families of children with or at risk for DD.
Laboratory strains of Escherichia coli: model citizens or deceitful delinquents growing old disgracefully?
Authors: Hobman Jon L. , Penn Charles W. , Pallen Mark J.
Published: May 2007

Escherichia coli stands unchallenged as biology's premier model organism. However, we propose, equipped with insights from the post‐genomic era, a contrary view: that microbiology's chief idol has feet of clay. E. coli laboratory strains, particularly E. coli K‐12, are far from model citizens, but instead degenerate and deceitful delinquents growing old disgracefully in our scientific institutions. E. coli K‐12 is neither archetype nor ancestor. In addition, it has a far from optimal provenance for a model organism, with strong grounds for believing that current versions of the strain are quite distinct from any original wild‐type free‐living ancestor. In addition, it is usually studied under conditions far removed from its natural habitats and in ignorance of the selective pressures that have shaped its evolution. Fortunately, a flood of information from high‐throughput genome sequencing, together with a new ‘eco‐evo’ view of this model organism, promises to help put K‐12 better into context.
How to build a fungal fruit body: from uniform cells to specialized tissue
Authors: Busch Silke , Braus Gerhard H.
Published: May 2007

It is a challenge in biology to explore the molecular and cellular mechanisms necessary to form a complex three‐dimensional structure composed of different cell types. Interesting models to study the underlying processes are fungi that can transform their wire‐like hyphal filaments into complex and sometimes container‐like fruit bodies. In the past, the role of developmental triggers and transcription factors was a major focus of research on fungal model organisms. In this issue of Molecular Microbiology, Nowrousian and collaborators report that fruit body development of the model organism Sordaria macrospora includes a novel player, a specific membrane protein of the endoplasmic reticulum that is not required for vegetative growth. This finding represents an important step towards connecting regulation of development with the co‐ordinated changes in cellular compartments.
Suicide prevention: disruption of apoptotic pathways by protozoan parasites
Authors: Carmen John C. , Sinai Anthony P.
Published: May 2007

The modulation of apoptosis has emerged as an important weapon in the pathogenic arsenal of multiple intracellular protozoan parasites. Cryptosporidium parvum, Leishmania spp., Trypanosoma cruzi, Theileria spp., Toxoplasma gondii and Plasmodium spp. have all been shown to inhibit the apoptotic response of their host cell. While the pathogen mediators responsible for this modulation are unknown, the parasites are interacting with multiple apoptotic regulatory systems to render their host cell refractory to apoptosis during critical phases of intracellular infection, including parasite invasion, establishment and replication. Additionally, emerging evidence suggests that the parasite life cycle stage impacts the modulation of apoptosis and possibly parasite differentiation. Dissection of the host–pathogen interactions involved in modulating apoptosis reveals a dynamic and complex interaction that recent studies are beginning to unravel.
Sequence features of substrates required for cleavage by GlpG, an Escherichia coli rhomboid protease
Authors: Akiyama Yoshinori , Maegawa Saki
Published: May 2007

Rhomboids are a family of serine proteases belonging to intramembrane cleaving proteases, which are supposed to catalyse proteolysis of a substrate protein within the membrane. It remains unclear whether substrates of the rhomboid proteases have a common sequence feature that allows specific cleavage by rhomboids. We showed previously that GlpG, the Escherichia coli rhomboid, can cleave a type I model membrane protein Bla‐LY2‐MBP having the second transmembrane region of lactose permease (LY2) at the extramembrane region in vivo and in vitro, and that determinants for proteolysis reside within the LY2 sequence. Here we characterized sequence features in LY2 that allow efficient cleavage by GlpG and identified two elements, a hydrophilic region encompassing the cleavage site and helix‐destabilizing residues in the downstream hydrophobic region. Importance of the positioning of helix‐destabilizers relative to the cleavage site was suggested. These two elements appear to co‐operatively promote proteolysis of substrates by GlpG. Finally, random mutagenesis of the cleavage site residues in combination with in vivo screening revealed that GlpG prefers residues with a small side chain and a negative charge at the P1 and P1′ sites respectively.
The RprY response regulator of Porphyromonas gingivalis
Authors: Duran‐Pinedo Ana E. , Nishikawa Kiyoshi , Duncan Margaret J.
Published: May 2007

Porphyromonas gingivalis is a Gram‐negative oral anaerobe associated with chronic adult periodontitis. Its ecological niche is the gingival crevice, where the organism adapts to the challenges of the infectious process such as host defence and bacterial products. Bacterial responses to environmental changes are partly regulated by two‐component signal transduction systems. Several intact systems were annotated in the genome of P. gingivalis, as well as an orphan regulator encoding a homologue of RprY, a response regulator from Bacteroides fragilis. With the goal of defining the environmental cues that activate RprY in P. gingivalis, we used several strategies to identify its regulon. Results from gene expression and DNA–protein binding assays identified target genes that were either involved in transport functions or associated with oxidative stress, and indicated that RprY can act as an activator and a repressor. RprY positively activated the primary sodium pump, NADH : ubiquinone oxidoreductase (NQR), and RprY protein also interacted with the promoter regions of nqrA genes from B. fragilis and Vibrio cholerae. Given that gingival bleeding and infiltration of host defence cells are symptoms of periodontal infection, iron products released from blood and reactive oxygen species from polymorphonuclear leucocytes may be potential inducers of the RprY regulon.
Chaperoning Anfinsen: the steric foldases
Authors: Pauwels Kris , Van Molle Inge , Tommassen Jan , Van Gelder Patrick
Published: May 2007

Some proteins are so much resistant to proteolysis and unfolding that they violate folding rules shared by the vast majority of proteins. These unusual proteins manage to fold into an active native conformation that is thermodynamically at best marginally, but often even less stable than the unfolded state. A huge energetic barrier traps these proteins kinetically in the folded state. The drawback of this situation is the need for a specialized chaperone that adds steric information to the proteins to cross this barrier on the folding pathway. Until now, our knowledge of these intriguing chaperones was restricted to the prodomains of secreted proteases, which function intramolecularly. Recent research has added more examples, which now include the membrane‐anchored lipase‐specific foldase and the pilus subunit specific chaperone, both acting intermolecularly. The case of the pilin chaperone is somewhat deviant in that steric information is definitely provided, but the pilus subunit adopts a thermodynamically favourable stable conformation.
A haem cofactor is required for redox and light signalling by the AppA protein of Rhodobacter sphaeroides
Authors: Han Yuchen , Meyer Martin H. F. , Keusgen Michael , Klug Gabriele
Published: May 2007

The AppA protein of Rhodobacter sphaeroides is unique in its ability to sense and transmit redox signals as well as light signals. By functioning as antagonist to the PpsR transcriptional repressor, it regulates the expression of photosynthesis genes in response to these environmental stimuli. Here we show binding of the cofactor haem to a domain in the C‐terminal part of AppA and redox activity of bound haem. This is supported by the findings that: (i) the C‐terminal domain of AppA (AppAΔN) binds to haemin agarose, (ii) AppAΔN isolated from Escherichia coli shows absorbance at 411 nm and absorbances at 424 nm and 556 nm after reduction with dithionite and (iii) AppAΔN can be reconstituted with haem in vitro. Expression of AppA variants in R. sphaeroides reveals that the haem binding domain is important for normal expression levels of photosynthesis genes and for normal light regulation in the presence of oxygen. The haem cofactor affects the interaction of the C‐terminal part of AppA to PpsR but also its interaction to the N‐terminal light sensing AppA‐BLUF domain. Based on this we present a model for the transmission of light and redox signals by AppA.
Identification of a region of FtsA required for interaction with FtsZ
Authors: Pichoff Sebastien , Lutkenhaus Joe
Published: May 2007

The assembly of the Z ring is the earliest step in bacterial cell division. In Escherichia coli this assembly requires either FtsA or ZipA which bind to a conserved, C‐terminal 17 amino acid motif in FtsZ and to the membrane. The FtsZ–ZipA interaction is well characterized; however, nothing is known about the region of FtsA involved in the interaction with FtsZ even though the FtsA–FtsZ interaction is nearly ubiquitous in Eubacteria. FtsA is proposed to bind to the membrane through its conserved C‐terminal amphiphatic helix before efficiently interacting with FtsZ. Based upon this model we designed a genetic screen to identify mutants specifically impaired for the FtsA–FtsZ interaction. The mutants obtained retain the ability to be targeted to the membrane but fail to be recruited to the Z ring or interact with FtsZ in the yeast two‐hybrid system. These mutants do not complement an ftsA‐depletion strain. Through this approach we have identified a region of FtsA containing some invariant residues which is required for binding to FtsZ. The results support our model that FtsA is targeted to the membrane before it interacts with FtsZ and demonstrates that this interaction plays an essential role in E. coli cell division.
Interaction of nitrogen nutrition and salinity in Grey poplar (Populus tremula × alba)
Authors: EHLTING B. , DLUZNIEWSKA P. , DIETRICH H. , SELLE A. , TEUBER M. , HÄNSCH R. , NEHLS U. , POLLE A. , SCHNITZLER J.‐P. , RENNENBERG H. , GESSLER A.
Published: May 2007

Salinity represents an increasing environmental problem in managed ecosystems. Populus spp. is widely used for wood production by short‐rotation forestry in fertilized plantations and can be grown on saline soil. Because N fertilization plays an important role in salt tolerance, we analysed Grey poplar (Populus tremula × alba, syn. Populus canescens) grown with either 1 mM nitrate or ammonium subjected to moderate 75 mM NaCl. The impact of N nutrition on amelioration of salt tolerance was analysed on different levels of N metabolism such as N uptake, assimilation and N (total N, proteins and amino compounds) accumulation. Na concentration increased in all tissues over time of salt exposure. The N nutrition‐dependent effects of salt exposure were more intensive in roots than in leaves. Application of salt reduced root increment as well as stem height increase and, at the same time, increased the concentration of total amino compounds more intensively in roots of ammonium‐fed plants. In leaves, salt treatment increased concentrations of total N more intensively in nitrate‐fed plants and concentrations of amino compounds independently of N nutrition. The major changes in N metabolism of Grey poplar exposed to moderate salt concentrations were detected in the significant increase of amino acid concentrations. The present results indicate that N metabolism of Grey poplar exposed to salt performed better when the plants were fed with nitrate instead of ammonium as sole N source. Therefore, nitrate fertilization of poplar plantations grown on saline soil should be preferred.
During measurements of root hydraulics with pressure probes, the contribution of unstirred layers is minimized in the pressure relaxation mode: comparison with pressure clamp and high‐pressure flowmeter
Authors: KNIPFER THORSTEN , DAS DEBASISH , STEUDLE ERNST
Published: May 2007

The effects of unstirred layers (USLs) at the endodermis of roots of young maize plants (Zea mays L.) were quantified, when measuring the water permeability of roots using a root pressure probe (RPP) in the pressure relaxation (PR) and pressure clamp (PC) modes. Different from PRs, PCs were performed by applying a constant pressure for certain periods of time. Experimental data were compared with results from simulations based on a convection versus diffusion (C/D) model, with the endodermis being the main barrier for solutes and water. Solute profiles in the stele were calculated as they occurred during rapid water flows across the root. The model quantitatively predicted the experimental finding of two distinct phases during PRs, in terms of a build‐up of concentration profiles in the stele between endodermis and xylem vessels. It also predicted that, following a PC, half‐times (T1/2) of PRs increased as the time used for clamping (and the build‐up of USLs) increased. Following PCs of durations of 15, 30 and 60 s, T1/2 increased by factors of between 2.5 and 7.0, and water permeability of roots (root hydraulic conductivity, Lpr) was reduced by the same factors. When root pressure was immediately taken back to the original equilibrium root pressure following a PC, there was a transient uptake of water into the root stele (transient increase of root pressure), and the size of transients rose with time of clamping, as predicted by the model. The results indicated that the ‘real’ hydraulic conductivity of roots should be measured during initial water flows, such as during the rapid phase of PRs, when the effect of USLs was minimized. It was discussed that ‘pressure‐propagation effects’ could not explain the finding of two phases during PRs. The results of USL effects threw some doubt on the use of PC and high‐pressure flowmeter (HPFM) techniques with roots, where rigorous estimates of USLs were still missing despite the fact that large quantities of water were forced across the root.
Timing of cotyledon damage affects growth and flowering in mature plants
Authors: HANLEY M. E. , FEGAN E. L.
Published: May 2007

Although the effects of herbivory on plant fitness are strongly linked to age, we understand little about how the timing of herbivory at the seedling stage affects growth and reproduction for plants that survive attack. In this study, we subjected six north‐western European, dicotyledonous grassland species (Leontodon autumnalis, Leontodon hispidus, Plantago lanceolata, Plantago major, Trifolium pratense and Trifolium repens) to cotyledon removal at 7, 14 and 21 d old. We monitored subsequent growth and flowering (number of inflorescences recorded, and time taken for first flowers to open) over a 107 d period. Cotyledon removal reduced growth during establishment (35 d) for all species, and a further three exhibited reduced growth at maturity. Four species developed fewer inflorescences, or had delayed flowering after cotyledon removal. Although early damage (7 d old) had the greatest long‐term effect on plant performance, responses varied according to the age at which the damage occurred and the species involved. Our results illustrate how growth and flowering into the mature phase is affected by cotyledon damage during different stages of seedling ontogeny, and we highlight the ways in which ontogenetic variation in seedling tolerance of tissue loss might impact upon plant fitness in mature plant communities.
Orthologous comparison in a gene‐rich region among grasses reveals stability in the sugarcane polyploid genome
Authors: Jannoo Nazeema , Grivet Laurent , Chantret Nathalie , Garsmeur Olivier , Glaszmann Jean Christophe , Arruda Paulo , D’Hont Angélique
Published: May 2007

Modern sugarcane (Saccharum spp.) is an important grass that contributes 60% of the raw sugar produced worldwide and has a high biofuel production potential. It was created about a century ago through hybridization of two highly polyploid species, namely S. officinarum and S. spontaneum. We investigated genome dynamics in this highly polyploid context by analyzing two homoeologous sequences (97 and 126 kb) in a region that has already been studied in several cereals. Our findings indicate that the two Saccharum species diverged 1.5–2 million years ago from one another and 8–9 million years ago from sorghum. The two sugarcane homoeologous haplotypes show perfect colinearity as well as high gene structure conservation. Apart from the insertion of a few retrotransposable elements, high homology was also observed for the non‐transcribed regions. Relative to sorghum, the sugarcane sequences displayed colinearity, with the exception of two genes present only in sorghum, and striking homology in most non‐coding parts of the genome. The gene distribution highlighted high synteny and colinearity with rice, and partial colinearity with each homoeologous maize region, which became perfect when the sequences were combined. The haplotypes observed in sugarcane may thus closely represent the ancestral Andropogoneae haplotype. This analysis of sugarcane haplotype organization at the sequence level suggests that the high ploidy in sugarcane did not induce generalized reshaping of its genome, thus challenging the idea that polyploidy quickly induces generalized rearrangement of genomes. These results also confirm the view that sorghum is the model of choice for sugarcane.
TECHNICAL NOTES ON CPP: Amygdala cannulation alters expression of cocaine conditioned place preference and locomotion in rats
Authors: Herzig Volker , Schmidt Werner J.
Published: May 2007

The effect of transient inactivation of the amygdala on expression of cocaine conditioned place preference (CPP) and locomotion was studied. We found that rats with bilateral but not unilateral amygdala cannula placement exhibited increased CPP expression during a vehicle and a cocaine test as well as increased cocaine‐induced hyper‐locomotion. We discuss the observed effects as being caused by the cannulation per se and we conclude that the applied cannulation produced an increased responsiveness of the amygdala by a yet undetermined mechanism.
ORIGINAL INVESTIGATIONS ON CPP: Effects of scopolamine on morphine‐induced conditioned place preference in mice
Authors: Tan Hua , Liu Ning , Wilson Fraser A. W. , Ma Yuanye
Published: May 2007

It is well known that the cholinergic system plays a crucial role in learning and memory. Psychopharmacological studies in humans and animals have shown that a systemic cholinergic blockade may induce deficits in learning and memory. Accumulated studies have indicated that learning and memory play an important role in drug addition. In the present study, in order to get a further understanding about the functions of the cholinergic system in drug‐related learning and memory, we examined the effects of scopolamine (0.5, 1.0 and 2.0 mg/kg) on morphine‐induced conditioned place preference (CPP). Two kinds of morphine exposure durations (4 days and 12 days) were used. The main finding was that all doses of scopolamine enhanced the extinction of morphine‐induced CPP in mice treated with morphine for 12 days. However, in mice treated with morphine for 4 days, all doses of scopolamine did not inhibit morphine‐induced CPP. The highest dose (2.0 mg/kg) of scopolamine even significantly delayed the extinction of morphine‐induced CPP. Our results suggest that the effects of a systemic cholinergic blockade on morphine‐induced CPP depend on the morphine exposure time.