bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene encoding a deubiquitinating enzyme is mutated in artesunate‐ and chloroquine‐resistant rodent malaria parasites§
Authors: Hunt Paul , Afonso Ana , Creasey Alison , Culleton Richard , Sidhu Amar Bir Singh , Logan John , Valderramos Stephanie G. , McNae Iain , Cheesman Sandra , Rosario Virgilio do , Carter Richard , Fidock David A. , Cravo Pedro
Published: June 2007

Artemisinin‐ and artesunate‐resistant Plasmodium chabaudi mutants, AS‐ART and AS‐ATN, were previously selected from chloroquine‐resistant clones AS‐30CQ and AS‐15CQ respectively. Now, a genetic cross between AS‐ART and the artemisinin‐sensitive clone AJ has been analysed by Linkage Group Selection. A genetic linkage group on chromosome 2 was selected under artemisinin treatment. Within this locus, we identified two different mutations in a gene encoding a deubiquitinating enzyme. A distinct mutation occurred in each of the clones AS‐30CQ and AS‐ATN, relative to their respective progenitors in the AS lineage. The mutations occurred independently in different clones under drug selection with chloroquine (high concentration) or artesunate. Each mutation maps to a critical residue in a homologous human deubiquitinating protein structure. Although one mutation could theoretically account for the resistance of AS‐ATN to artemisinin derivates, the other cannot account solely for the resistance of AS‐ART, relative to the responses of its sensitive progenitor AS‐30CQ. Two lines of Plasmodium falciparum with decreased susceptibility to artemisinin were also selected. Their drug‐response phenotype was not genetically stable. No mutations in the UBP‐1 gene encoding the P. falciparum orthologue of the deubiquitinating enzyme were observed. The possible significance of these mutations in parasite responses to chloroquine or artemisinin is discussed.
SaPI operon I is required for SaPI packaging and is controlled by LexA
Authors: Úbeda Carles , Maiques Elisa , Tormo MaÁngeles , Campoy Susana , Lasa Íñigo , Barbé Jordi , Novick Richard P. , Penadés José R.
Published: June 2007

Transfer of Staphylococcus aureus pathogenicity islands (SaPIs) is directly controlled by the cellular repressor LexA. We have found that transcription of the SaPIbov1 operon I is repressed by LexA and is therefore SOS‐induced. Two copies of the LexA binding site consensus (Cheo box) are present in the 5′ region of this operon, at the same location in all of 15 different SaPIs analysed. Both of these boxes bind LexA protein. Furthermore, replacement of the chromosomal lexA with a non‐cleavable mutant LexA (G94E) greatly diminished expression of SaPIbov1 operon I and differentially reduced the production of SaPI transducing particles in comparison with the production of plaque‐forming particles. In concordance with this finding, deletion of operon I blocked the formation of SaPI transducing particles but had no effect on replication of the island. Operon I contains a gene encoding a homologue of the phage terminase small subunit plus two other genes that direct the assembly of the small sized SaPIbov1 capsids. Interestingly, mutations affecting the latter two genes were not defective in SaPI transfer, but rather encapsidated the island in full‐sized phage heads, which would have to contain a multimeric SaPI genome.
Critical roles for the digestive vacuole plasmepsins of Plasmodium falciparum in vacuolar function
Authors: Bonilla J. Alfredo , Bonilla Tonya D. , Yowell Charles A. , Fujioka Hisashi , Dame John B.
Published: June 2007

Knockout mutants of Plasmodium falciparum lacking pfpm1, pfpm2 and pfhap (triple‐PM KO), and mutants lacking all four digestive vacuole (DV) plasmepsins (pfpm4, pfpm1, pfpm2 and pfhap; quadruple‐PM KO), were prepared by double cross‐over integration effecting chromosomal deletions of up to 14.6 kb. The triple‐PM KO was similar to the parental line (3D7) in growth rate, morphology and sensitivity to proteinase inhibitors. The quadruple‐PM KO showed a significantly slower rate of growth in standard medium, which manifested as delayed schizont maturation accompanied by reduced formation of haemozoin. In amino acid‐limited medium, the reduction in growth rate of the quadruple‐PM KO was pronounced. The sensitivity of both the triple‐ and quadruple‐PM KOs to six different HIV aspartic proteinase inhibitors was comparable to that of 3D7, thus establishing that the DV plasmepsins were not the primary targets of the antimalarial activity of these clinically important compounds. Electron microscopic analysis revealed the presence of multilamellar bodies resembling ceroid in the DV of the quadruple‐PM KO, and intermediates of the autophagic pathway accumulated as determined by Western blot analysis. Thus, the DV plasmepsins, although not essential, contribute significantly to the fitness of the parasite and are required for efficient degradation of endosomal vesicles delivered to the DV.
Responses of Pseudomonas aeruginosa to low oxygen indicate that growth in the cystic fibrosis lung is by aerobic respiration
Authors: Alvarez‐Ortega Carolina , Harwood Caroline S.
Published: June 2007

Pseudomonas aeruginosa in the lungs of cystic fibrosis patients grows to high densities in mucopurulent material that is depleted in oxygen. Some have concluded that growth in these circumstances is dependent on anaerobic nitrate respiration. Here we present data in favour of the alternative hypothesis that microaerobic respiration is the predominant mode of P. aeruginosa growth in the cystic fibrosis lung. We found that P. aeruginosa strain PAO1 and a mucoid derivative of strain PAO1 each grew at dissolved oxygen concentrations of less than 3 μM. This is lower than the concentration of oxygen that has been measured in hypoxic cystic fibrosis mucous. A transcriptome analysis comparing cells grown under aerobic conditions (185 μM dissolved oxygen) with cells grown with 20 μM or 3 μM dissolved oxygen, or anaerobically with nitrate, revealed that overlapping sets of genes are expressed depending on oxygen availability. This suggests that P. aeruginosa responds to changes in oxygen concentration along a continuum rather than having a discrete low oxygen regulon. Any one of three high affinity terminal oxidases that P. aeruginosa encodes supported microaerobic growth. A triple mutant lacking all three of these oxidases failed to grow at low oxygen and formed abnormal biofilms.
A proline iminopeptidase gene upregulated in planta by a LuxR homologue is essential for pathogenicity of Xanthomonas campestris pv. campestris
Authors: Zhang Lili , Jia Yantao , Wang Li , Fang Rongxiang
Published: June 2007

Expression of bacterial genes is often regulated by complex mechanisms, some of which involve host cues. Analysis of the Xanthomonas campestris pv. campestris (Xcc) genome sequence revealed the presence of an xccR/pip locus. The upstream gene xccR is a luxR homologue, while pip codes for a proline iminopeptidase. A lux box‐like element, named luxXc box, locates in the pip promoter region. In this work, we show that disruption of either xccR or pip resulted in significantly attenuated virulence of Xcc. Under medium culture conditions, the pip expression was significantly enhanced by overexpression of XccR and the luxXc box is necessary for this enhancement. We further show that expression of a pip promoter–gusA fusion either inserted in the bacterial chromosome or resided in a plasmid was markedly induced when the bacteria grew in planta. Disruption of either xccR or the luxXc box abolished the in planta induction, while disruption of pip enhanced the induction. Taken together, these data demonstrate that pip is indispensable for Xcc virulence and suggest a model for Xcc–host interaction in which the pathogen senses some host factor(s) to activate XccR that subsequently interacts with the luxXc box to induce the expression of pip for facilitating Xcc infection.
Temporal separation of distinct differentiation pathways by a dual specificity Rap‐Phr system in Bacillus subtilis
Authors: Smits Wiep Klaas , Bongiorni Cristina , Veening Jan‐Willem , Hamoen Leendert W. , Kuipers Oscar P. , Perego Marta
Published: June 2007

In bacterial differentiation, mechanisms have evolved to limit cells to a single developmental pathway. The establishment of genetic competence in Bacillus subtilis is controlled by a complex regulatory circuit that is highly interconnected with the developmental pathway for spore formation, and the two pathways appear to be mutually exclusive. Here we show by in vitro and in vivo analyses that a member of the Rap family of proteins, RapH, is activated directly by the late competence transcription factor ComK, and is capable of inhibiting both competence and sporulation. Importantly, RapH is the first member of the Rap family that demonstrates dual specificity, by dephosphorylating the Spo0F∼P response regulator and inhibiting the DNA‐binding activity of ComA. The protein thus acts at the stage where competence is well initiated, and prevents initiation of sporulation in competent cells as well as contributing to the escape from the competent state. A deletion of rapH induces both differentiation pathways and interferes with their temporal separation. Together, these results indicate that RapH is an integral part of a multifactorial regulatory circuit affecting the cell's decision between distinct developmental pathways.
DNA and origin region segregation are not affected by the transition from rod to sphere after inhibition of Escherichia coli MreB by A22
Authors: Karczmarek Aneta , Baselga Rocío Martínez‐Arteaga , Alexeeva Svetlana , Hansen Flemming G. , Vicente Miguel , Nanninga Nanne , Den Blaauwen Tanneke
Published: June 2007

The bacterial actin homologue MreB forms a helix underneath the cytoplasmic membrane and was shown to be essential in the morphogenesis of the rod‐shaped cells. Additionally, MreB was implicated to be involved in DNA segregation. However, in our hands the mreBCD deletion strain (PA340‐678) grew without apparent DNA segregation defect, suggesting that the reported chromosome segregation inhibition could be caused by a temporarily effect of MreB inhibition or depletion. To assess the involvement of MreB in DNA segregation during the transition from rod to sphere, we compared the effect of A22 and the PBP2 inhibitor mecillinam on the percentage of cells with segregated nucleoids and the number of oriC foci in wild‐type Escherichia coli cells. Cells became spherical in the same time window during both treatments and we could not detect any difference in the chromosome or oriC segregation between these two treatments. Additionally, flow cytometric analyses showed that A22 and mecillinam treatment gave essentially the same chromosome segregation pattern. We conclude that MreB is not directly involved in DNA segregation of E. coli.
Extracellular respiration
Authors: Gralnick Jeffrey A. , Newman Dianne K.
Published: June 2007

Although it has long been known that microbes can generate energy using diverse strategies, only recently has it become clear that a growing number involve electron transfer to or from extracellular substrates. The best‐known example of what we will term ‘extracellular respiration’ is electron transfer between microbes and minerals, such as iron and manganese (hydr)oxides. This makes sense, given that these minerals are sparingly soluble. What is perhaps surprising, however, is that a number of substrates that might typically be classified as ‘soluble’ are also respired at the cell surface. There are several reasons why this might be the case: the substrate, in its ecological context, might be associated with a solid surface and thus effectively insoluble; the substrate, while soluble, might simply be too large to transport inside the cell; or the substrate, while benign in one redox state, might become toxic after it is metabolized. In this review, we discuss various examples of extracellular respiration, paying particular attention to what is known about the molecular mechanisms underlying these processes. As will become clear, much remains to be learned about the biochemistry, cell biology and regulation of extracellular respiration, making it a rich field of study for molecular microbiologists.
The essential YycFG two‐component system controls cell wall metabolism in Bacillus subtilis
Authors: Bisicchia Paola , Noone David , Lioliou Efthimia , Howell Alistair , Quigley Sarah , Jensen Thomas , Jarmer Hanne , Devine Kevin M.
Published: June 2007

Adaptation of bacteria to the prevailing environmental and nutritional conditions is often mediated by two‐component signal transduction systems (TCS). The Bacillus subtilis YycFG TCS has attracted special attention as it is essential for viability and its regulon is poorly defined. Here we show that YycFG is a regulator of cell wall metabolism. We have identified five new members of the YycFG regulon: YycF activates expression of yvcE, lytE and ydjM and represses expression of yoeB and yjeA. YvcE(CwlO) and LytE encode endopeptidase‐type autolysins that participate in peptidoglycan synthesis and turnover respectively. We show that a yvcE lytE double mutant strain is not viable and that cells lacking LytE and depleted for YvcE exhibit defects in lateral cell wall synthesis and cell elongation. YjeA encodes a peptidoglycan deacetylase that modifies peptidoglycan thereby altering its susceptibility to lysozyme digestion and YdjM is also predicted to have a role in cell wall metabolism. A genetic analysis shows that YycFG essentiality is polygenic in nature, being a manifestation of disrupted cell wall metabolism caused by aberrant expression of a number of YycFG regulon genes.
Respiration of metal (hydr)oxides by Shewanella and Geobacter: a key role for multihaem c‐type cytochromes
Authors: Shi Liang , Squier Thomas C. , Zachara John M. , Fredrickson James K.
Published: June 2007

Dissimilatory reduction of metal (e.g. Fe, Mn) (hydr)oxides represents a challenge for microorganisms, as their cell envelopes are impermeable to metal (hydr)oxides that are poorly soluble in water. To overcome this physical barrier, the Gram‐negative bacteria Shewanella oneidensis MR‐1 and Geobacter sulfurreducens have developed electron transfer (ET) strategies that require multihaem c‐type cytochromes (c‐Cyts). In S. oneidensis MR‐1, multihaem c‐Cyts CymA and MtrA are believed to transfer electrons from the inner membrane quinone/quinol pool through the periplasm to the outer membrane. The type II secretion system of S. oneidensis MR‐1 has been implicated in the reduction of metal (hydr)oxides, most likely by translocating decahaem c‐Cyts MtrC and OmcA across outer membrane to the surface of bacterial cells where they form a protein complex. The extracellular MtrC and OmcA can directly reduce solid metal (hydr)oxides. Likewise, outer membrane multihaem c‐Cyts OmcE and OmcS of G. sulfurreducens are suggested to transfer electrons from outer membrane to type IV pili that are hypothesized to relay the electrons to solid metal (hydr)oxides. Thus, multihaem c‐Cyts play critical roles in S. oneidensis MR‐1‐ and G. sulfurreducens‐mediated dissimilatory reduction of solid metal (hydr)oxides by facilitating ET across the bacterial cell envelope.
An atypical receiver domain controls the dynamic polar localization of the Myxococcus xanthus social motility protein FrzS
Authors: Fraser James S. , Merlie John P. , Echols Nathaniel , Weisfield Shellie R. , Mignot Tâm , Wemmer David E. , Zusman David R. , Alber Tom
Published: June 2007

The Myxococcus xanthus FrzS protein transits from pole‐to‐pole within the cell, accumulating at the pole that defines the direction of movement in social (S) motility. Here we show using atomic‐resolution crystallography and NMR that the FrzS receiver domain (RD) displays the conserved switch Tyr102 in an unusual conformation, lacks the conserved Asp phosphorylation site, and fails to bind Mg2+ or the phosphoryl analogue, Mg2+·BeF3. Mutation of Asp55, closest to the canonical site of RD phosphorylation, showed no motility phenotype in vivo, demonstrating that phosphorylation at this site is not necessary for domain function. In contrast, the Tyr102Ala and His92Phe substitutions on the canonical output face of the FrzS RD abolished S‐motility in vivo. Single‐cell fluorescence microscopy measurements revealed a striking mislocalization of these mutant FrzS proteins to the trailing cell pole in vivo. The crystal structures of the mutants suggested that the observed conformation of Tyr102 in the wild‐type FrzS RD is not sufficient for function. These results support the model that FrzS contains a novel ‘pseudo‐receiver domain’ whose function requires recognition of the RD output face but not Asp phosphorylation.
Non-adiabatic oscillations of red giants
Authors: Xiong D. R. , Deng L.
Published: June 2007

Using our non-local time-dependent theory of convection, the linear non-adiabatic oscillations of 10 evolutionary model series with masses of 1–3 M⊙ are calculated. The results show that there is a red giant instability strip in the lower temperature side of the Hertzsprung–Russell diagram which goes along the sequences of the red giant branch and the asymptotic giant branch. For red giants of lower luminosities, pulsation instability is found at high order overtones; the lower order modes from the fundamental to the second overtone are stable. Towards higher luminosity and lower effective temperature, instability moves to lower order modes, and the amplitude growth rate of oscillations also grows. At the high luminosity end of the strip, the fundamental and the first overtone become unstable, while all the modes above the fourth order become stable. The excitation mechanisms have been studied in detail. It is found that turbulent pressure plays a key role for excitation of red variables. The frozen convection approximation is unavailable for the low temperature stars with extended convective envelopes. In any case, this approximation can explain neither the red edge of the Cepheid instability strip, nor the blue edge of the pulsating red giant instability strip. An analytic expression of a pulsation constant as a function of stellar mass, luminosity and effective temperature is presented from this work.
A large-scale extinction map of the Galactic Anticentre from 2MASS
Authors: Froebrich D. , Murphy G. C. , Smith M. D. , Walsh J. , Del Burgo C.
Published: June 2007

We present a 127 × 63-deg2 extinction map of the Anticentre of the Galaxy, based on 〈J−H〉 and 〈H−K〉 colour excess maps from the Two-Micron All-Sky Survey. This 8001-deg2 map with a resolution of 4 arcmin is provided as online material. The colour excess ratio 〈J−H〉/〈H−K〉 is used to determine the power-law index of the reddening law (β) for individual regions contained in the area (e.g. Orion, Perseus, Taurus, Auriga, Monoceros, Camelopardalis, Cassiopeia). On average we find a dominant value of β= 1.8 ± 0.2 for the individual clouds, in agreement with the canonical value for the interstellar medium. We also show that there is an internal scatter of β values in these regions, and that in some areas more than one dominant β values are present. This indicates large-scale variations in the dust properties. The analysis of the AV values within individual regions shows a change in the slope of the column density distribution with distance. This can be attributed either to a change in the governing physical processes in molecular clouds on spatial scales of about 1 pc or to an AV dilution with distance in our map.
Spatially resolved kinematics and stellar populations of brightest cluster and group galaxies
Authors: Brough S. , Proctor Robert , Forbes Duncan A. , Couch Warrick J. , Collins C. A. , Burke D. J. , Mann R. G.
Published: June 2007

We present an examination of the kinematics and stellar populations of a sample of three brightest group galaxies (BGGs) and three brightest cluster galaxies (BCGs) in X-ray groups and clusters. We have obtained high signal-to-noise ratio Gemini/Gemini South Multi-Object Spectrograph (GMOS) long-slit spectra of these galaxies and use Lick indices to determine ages, metallicities and α-element abundance ratios out to at least their effective radii. We find that the BGGs and BCGs have very uniform masses, central ages and central metallicities. Examining the radial dependence of their stellar populations, we find no significant velocity dispersion, age, or α-enhancement gradients. However, we find a wide range of metallicity gradients, suggesting a variety of formation mechanisms. The range of metallicity gradients observed is surprising, given the homogeneous environment these galaxies probe and their uniform central stellar populations. However, our results are inconsistent with any single model of galaxy formation and emphasize the need for more theoretical understanding of both the origins of metallicity gradients and galaxy formation itself. We postulate two possible physical causes for the different formation mechanisms.
Adult‐onset glycogen storage disease type 2: clinico‐pathological phenotype revisited
Authors: Schoser B. G. H. , Müller‐Höcker J. , Horvath R. , Gempel K. , Pongratz D. , Lochmüller H. , Müller‐Felber W.
Published: June 2007

The need for clinical awareness and diagnostic precision of glycogen storage disease type 2 (GSD2) has increased, as enzyme replacement therapy has become available. So far, only small series have reported the muscle pathology of late‐onset GSD2. We reassessed 43 muscle biopsies of 38 GSD2 patients. In all patients the diagnosis of GSD2 has been established by biochemistry and/or mutational analysis of the GAA gene. Additionally to the expected morphological features, ultrastructural analysis revealed a high incidence of autophagic vacuoles, lipofuscin debris, structural Z‐line disorganization and histological neurogenic‐like pattern that were not thoroughly appreciated, previously. Comparing age at onset and morphology, excessive vacuolar and autophagic myopathy and mitochondrial disorganization of virtually all fibres is common in infants. At juvenile onset, a more moderate vacuolization without significant differences in overall morphology is notable. At late‐onset, the spectrum of vacuolar myopathy is more divergent, ranging from almost normal to severe. Here pronounced secondary alterations are observed that include lipofuscin debris, autophagic vacuoles with residual lysosomal bodies and granular inclusions, structural mitochondrial and Z‐line texture alterations. Moreover, there is a high incidence of subtle neurogenic‐like alteration in all subtypes. Nineteen patients were genetically tested; in 15 patients the common leaky splicing mutation c.−45T>G (or IVS1–13T>G) in intron1 of the GAA gene was found on at least one allele, facilitating genetic screening. In our patients, GAA genotype appears not to be associated with secondary alterations such as autophagic vacuoles, structural alterations or neurogenic‐like changes. These findings may have implications for our understanding of the pathogenesis of GSD2 and for assessing therapeutic success of enzyme replacement therapy.
Rab6 is increased in Alzheimer's disease brain and correlates with endoplasmic reticulum stress
Authors: Scheper W. , Hoozemans J. J. M. , Hoogenraad C. C. , Rozemuller A. J. M. , Eikelenboom P. , Baas F.
Published: June 2007

Alzheimer's disease (AD) is characterized by deposits of aggregated proteins. Accumulation of aggregation‐prone proteins activates protein quality control mechanisms, such as the unfolded protein response (UPR) in the endoplasmic reticulum (ER). We previously reported upregulation of the UPR marker BiP in AD brain. In this study, we investigated the small GTPase Rab6, which is involved in retrograde Golgi–ER trafficking and may function as a post‐ER quality control system. Using immunohistochemistry and semiquantitative Western blotting, the expression of Rab6 was analysed in hippocampus, entorhinal and temporal cortex of 10 AD patients and six nondemented control subjects. Rab6 is upregulated in AD temporal cortex from Braak stage 3/4, the same stage that UPR activation is found. We observe increased neuronal Rab6 immunoreactivity in all brain areas examined. Although some neurones show colocalization of immunoreactivity for Rab6 and hyperphosphorylated tau, strong Rab6 staining does not colocalize with tangles. We find a highly significant correlation between the Rab6 and BiP levels. In vitro data show that Rab6 is not upregulated as a result of UPR activation or proteasome inhibition indicating an independent regulatory mechanism. Our data suggest that ER and post‐ER protein quality control mechanisms are activated early in the pathology of AD.
Options and limitations in studies of successive pregnancy outcomes: an overview
Authors: Basso Olga
Published: June 2007

This paper provides a brief overview of options and limitations in studies of successive pregnancy outcomes, largely derived from the author's personal experience on Danish registries. The issues discussed here by no means constitute an exhaustive list, but aim at providing an introduction for researchers interested in this topic.
Research on recurrent pregnancy complications: a clinician's perspective
Authors: Smulian John C.
Published: June 2007

Research on recurrent pregnancy complications is essential to help clinicians provide appropriate counselling and guide the management of patients with a history of adverse pregnancy outcomes. However, recurrence research is complex, in both its execution and interpretation. The paucity of appropriate data sets accessible for study of recurrent pregnancy outcomes presents significant challenges in performing recurrence research. This is further compounded by the different perspectives on recurrence between epidemiologists and clinicians. The interpretation of risk, whether it is absolute risk, relative risk or population‐attributable fraction, underlies the often opposing perspectives of researchers and clinicians. Because clinicians acutely feel the need to provide appropriate counselling and management strategies when there has been a previous pregnancy complication, it is necessary that all those involved in research and care for these women work together to address gaps in our knowledge for recurrent pregnancy outcomes. In this way, we can develop a better understanding of disease processes, counsel patients better, design management plans and, ultimately, achieve better outcomes for our patients.
Stillbirth recurrence in a population of relatively low‐risk mothers
Authors: Sharma Puza P. , Salihu Hamisu M. , Kirby Russel S.
Published: June 2007

We sought to estimate the risk of stillbirth recurrence among relatively low‐risk women, a group defined as maternal age <35 years; absence of congenital anomalies; gestational age range of 20–44 weeks inclusive; singleton births; and non‐smokers. The Missouri maternally linked data containing births from 1978 to 1997 were used for the study. We identified the study group (low‐risk gravidae who experienced a stillbirth in the first pregnancy) and a comparison group (low‐risk gravidae who delivered a live birth in their first pregnancy) and compared the stillbirth risks in the second pregnancy between both groups. Analysis was based on 261 384 women with information on first and second pregnancies [1050 (0.5%) women with stillbirth].

Of the 947 cases of stillbirth in the second pregnancy, 20 cases occurred in women with a history of stillbirth (stillbirth rate 19.0 per 1000 births) and 927 in the comparison group (stillbirth rate 3.6 per 1000 births; P < 0.001). The adjusted risk of stillbirth was almost six times higher in women with a prior stillbirth (hazard ratio [HR] 5.8, [95% CI 3.7, 9.0]). Analysis by stillbirth subtype in the second pregnancy showed that history of stillbirth conferred greater risk for subsequent early (fetal deaths between 20 and 28 weeks) (HR 10.3, [95% CI 6.1, 17.2]) than late stillbirths (fetal deaths at ≥29 weeks) (HR 2.5, [95% CI 1.0, 6.0]); and for intrapartum (HR 12.2, [95% CI 4.5, 33.3]) than antepartum (HR 4.2, [95% CI 2.3, 7.7]) stillbirths. Among relatively low‐risk women, history of stillbirth was associated with increased recurrence, with substantial heterogeneity by timing of stillbirth.
The effects and mechanisms of primiparity on the risk of pre‐eclampsia: a systematic review
Authors: Luo Zhong‐Cheng , An Na , Xu Hai‐Rong , Larante Amelie , Audibert Francois , Fraser William D.
Published: June 2007

Pre‐eclampsia has been dubbed as ‘a disease of primiparity’. However, the effects and mechanisms of the association of primiparity with pre‐eclampsia have not been clearly defined. We conducted a systematic review of studies evaluating the effect of primiparity on the risk of pre‐eclampsia, and studies (published between January 1966 and July 2005) on the mechanisms underlying such an association. A total of 26 original studies were identified and a meta‐analysis carried out for the risk of pre‐eclampsia among primiparous vs. multiparous women.

Variably (1.4–5.5 times) higher risks of pre‐eclampsia were observed in primiparous women in all studies, with a summary odds ratio (OR) of 2.42 [95% CI 2.16, 2.71]. The adjusted ORs were larger than crude ORs in all but one study after various adjustments. Except for abundant epidemiological evidence in support of the immune maladaptation theory, only four original studies examined the actual mechanisms of such primiparity‐associated risk. Two (small) studies suggested differences in immunological responses in the aetiology of pre‐eclampsia in primiparous vs. multiparous women. Two recent studies indicated that differences in angiogenic factor profile or reactivity to insulin resistance in early pregnancy may explain the elevated pre‐eclampsia risk in first pregnancies. In conclusion, primiparity is associated with approximately 2.4‐fold elevated risk of pre‐eclampsia. Although immune maladaptation is generally considered as the basis to explain such an elevated risk, few data are available on immune maladaptation parameters in primiparous vs. multiparous pregnancies. Available data are insufficient to interpret the mechanisms of such primiparity‐associated excess risk of pre‐eclampsia.
Cysteine proteinase 30 (CP30) and antibody response to CP30 in serum and vaginal washes of symptomatic and asymptomatic Trichomonas vaginalis‐infected women
Authors: YADAV M. , DUBEY M. L. , GUPTA I. , MALLA N.
Published: June 2007

Infection with Trichomonas vaginalis may be asymptomatic or with symptoms suggestive of vaginitis. Because cysteine proteinase 30 (CP30) of T. vaginalis is known to be a virulence marker that plays a role in cytoadherence, the aim of this study was to analyse the presence of CP30 and antibody to CP30 in clinical samples of symptomatic and asymptomatic infected women. CP30 was detected in all the serum and vaginal washes (VWs) of symptomatic women and in 65% of the serum and 80% of the VWs of asymptomatic women. This suggested that the majority of asymptomatic women also exhibit CP30 in the serum and VWs. Antibody to CP30 was detected in all the serum samples of symptomatic and asymptomatic women and in the VWs of only 54·5% of the symptomatic and 35% of the asymptomatic women. Antibody to CP30 was also detected in 3/20 of the serum samples and in none of the VWs from uninfected women. Significantly higher amounts of antibody (mean OD values) were observed in serum and VWs of symptomatic as compared to asymptomatic and healthy women (P < 0·001). These results indicate that besides CP30, other factors may also be playing a role in leading to symptomatic infection, because CP30 was detected in clinical samples from all the symptomatic and the majority of the asymptomatic women. Although anti‐CP30 antibodies do not appear to be protective, detection of antibody to CP30 antigen in serum samples may be used as a diagnostic tool.
Determining the limitations and regulation of photosynthetic energy transduction in leaves
Authors: BAKER NEIL R. , HARBINSON JEREMY , KRAMER DAVID M.
Published: June 2007

The light‐dependent production of ATP and reductants by the photosynthetic apparatusin vivoinvolves a series of electron and proton transfers. Consideration is given as to how electron fluxes through photosystem I (PSI), using absorption spectroscopy, and through photosystem II (PSII), using chlorophyll fluorescence analyses, can be estimatedin vivo. Measurements of light‐induced electrochromic shifts using absorption spectroscopy provide a means of analyzing the proton fluxes across the thylakoid membranesin vivo. Regulation of these electron and proton fluxes is required for the thylakoids to meet the fluctuating metabolic demands of the cell. Chloroplasts exhibit a wide and flexible range of mechanisms to regulate electron and proton fluxes that enable chloroplasts to match light use for ATP and reductant production with the prevailing metabolic requirements. Non‐invasive probing of electron fluxes through PSI and PSII, and proton fluxes across the thylakoid membranes can provide insights into the operation of such regulatory processesin vivo.
Photosynthesis and resource distribution through plant canopies
Authors: NIINEMETS ÜLO
Published: June 2007

Plant canopies are characterized by dramatic gradients of light between canopy top and bottom, and interactions between light, temperature and water vapour deficits. This review summarizes current knowledge of potentials and limitations of acclimation of foliage photosynthetic capacity (Amax) and light‐harvesting efficiency to complex environmental gradients within the canopies. Acclimation of Amax to high light availability involves accumulation of rate‐limiting photosynthetic proteins per unit leaf area as the result of increases in leaf thickness in broad‐leaved species and volume : total area ratio and mesophyll thickness in species with complex geometry of leaf cross‐section. Enhancement of light‐harvesting efficiency in low light occurs through increased chlorophyll production per unit dry mass, greater leaf area per unit dry mass investment in leaves and shoot architectural modifications that improve leaf exposure and reduce within‐shoot shading. All these acclimation responses vary among species, resulting in species‐specific use efficiencies of low and high light. In fast‐growing canopies and in evergreen species, where foliage developed and acclimated to a certain light environment becomes shaded by newly developing foliage, leaf senescence, age‐dependent changes in cell wall characteristics and limited foliage re‐acclimation capacity can constrain adjustment of older leaves to modified light availabilities. The review further demonstrates that leaves in different canopy positions respond differently to dynamic fluctuations in light availability and to multiple environmental stresses. Foliage acclimated to high irradiance respond more plastically to rapid changes in leaf light environment, and is more resistant to co‐occurring heat and water stress. However, in higher light, co‐occurring stresses can more strongly curb the efficiency of foliage photosynthetic machinery through reductions in internal diffusion conductance to CO2. This review demonstrates strong foliage potential for acclimation to within‐canopy environmental gradients, but also highlights complex constraints on acclimation and foliage functioning resulting from light × foliage age interactions, multiple environmental stresses, dynamic light fluctuations and species‐specific leaf and shoot structural constraints.
Introductions of non‐native plant pathogens into Great Britain, 1970–2004
Authors: Jones D. R. , Baker R. H. A.
Published: June 2007

An analysis of records of plant pathogens first identified in Great Britain from 1970 to 2004 (inclusive) was undertaken to determine the numbers of new species that have become established over time. Results show that the numbers of newly recorded pathogens have not varied significantly. Of the 234 pathogens recorded for the first time between 1970 and 2004, 157 were fungi, 27 were oomycetes, 26 were viruses, 23 were bacteria, and one was a phytoplasma. Approximately 53% of pathogens were found on ornamental crops, 16% on horticultural crops, 15% on wild native species, 12% on agricultural crops, 2% on pasture plants and 2% on exotic forestry tree species. Where the origin of introductions was known or strongly suspected, 47% came from the Netherlands. About 38% of newly recorded pathogens with information on the location of first record were discovered in the South East region of England. Plant Pathologists regarded 19% of all new pathogens as important because of actual or potential economic/environmental losses. The results indicate that the numbers of new or important pathogens establishing in recent years are not increasing and that most new findings are associated with ornamental plants.
Effects of inoculum potential, shading and soil temperature on root infection of oil palm seedlings by the basal stem rot pathogen Ganoderma boninense
Authors: Rees R. W. , Flood J. , Hasan Y. , Cooper R. M.
Published: June 2007

Ganoderma boninense causes severe losses to oil palm in South East Asia. The disease typically manifests itself as basal stem rot, but there remains controversy over the route of infection and source of inoculum. Using isolates differing in aggressiveness, infection via roots was confirmed; it was also shown that large inoculum provided as Ganoderma‐infested palm‐ or rubber‐wood blocks (12 × 6 × 6 cm) is necessary for soil infection of seedlings after 6–8 months. Smaller blocks (3 × 3 × 3 cm) produced rapid (≤ 3 months) infection of roots and lower stem when physically attached to roots. Therefore fragmentation of infested palm wood from a felled, mature plantation before subsequent replanting may provide inoculum. Failure of G. boninense to grow through non‐sterile soil or organic debris from frond bases, suggests it is a poor competitor and that roots must contact inoculum directly. Severe disease occurred after 8 months on inoculated seedlings under shade, but not on seedlings exposed to sun. Soil temperatures in sunlight frequently rose above 40°C and reached 45°C, whereas in shade they never exceeded 32°C. Ganoderma boninense is probably inhibited in exposed soil since optimal growth in vitro was 25–30°C, and there was no recovery from 45°C. Soil temperature may explain why symptoms often first appear in mature plantations when canopy formation creates shade. Infection is not peculiar to senescing palms but can occur throughout the growth cycle.
Single‐strand conformation polymorphism (SSCP), cloning and sequencing reveal a close association between related molecular variants of Grapevine virus A (GVA) and Shiraz disease in South Africa
Authors: Goszczynski D. E.
Published: June 2007

When a recently discovered 234‐nt fragment of the Grapevine virus A (GVA) genome, located in ORF3, was used in single‐strand conformation polymorphism (SSCP), it produced patterns of DNA bands which were indicative of GVA variants of molecular group II. This technique of rapid identification of variants of group II was applied to the study of GVA variants in various grapevines with different Shiraz disease (SD) status. The results, supported by nucleotide sequence data, revealed that GVA variants of molecular group II are closely associated with SD in South Africa, and showed that variants of group III are commonly present in SD‐susceptible grapevines that consistently do not exhibit symptoms of this disease.
Sensitivity of Phytophthora infestans to mandipropamid and the effect of enforced selection pressure in the field
Authors: Cohen Y. , Rubin E. , Hadad T. , Gotlieb D. , Sierotzki H. , Gisi U.
Published: June 2007

Sensitivity to the new carboxylic acid amide (CAA) fungicide mandipropamid (MPD) in Phytophthora infestans was measured for isolates collected between 1989 and 2002 in Israel prior to the commercial use of MPD (baseline sensitivity, 44 isolates), and from MPD‐treated (25 isolates) and untreated fields (215 isolates) in nine European countries and Israel between 2001 and 2005. All isolates were sensitive to MPD, with EC50 values ranging between 0·02 and 2·98 µg mL−1. Plastic‐tunnel (UK), shade‐house (Israel) and field experiments (Israel) conducted during 2001–05 showed that enforced selection pressure, applied preventively or curatively, imposed by repeated sublethal (5 µg mL−1) or excessive (500–1000 µg mL−1) doses of MPD on mixed isolates of P. infestans produced no isolates resistant to the compound. The results of this study indicate that the probability of a buildup of resistant sub‐populations of P. infestans to mandipropamid in the field is low.
Development of an Arabidopsis thaliana‐based bioassay for investigating seed colonization by mycotoxigenic Aspergillus species
Authors: Hammond T. M. , Tsitsigiannis D. I. , Keller N. P.
Published: June 2007

Seeds of Arabidopsis thaliana are hosts for three mycotoxin‐producing Aspergillus species, A. flavus, A. nidulans and A. parasiticus, enabling an Aspergillus‐Arabidopsis infection (AAI) assay to be developed. The AAI assay involved inoculation of 10‐ to 12‐mg aliquots of uniformly cultivated, surface‐sterilized A. thaliana seeds in microcentrifuge tubes. Use of microcentrifuge tubes facilitated qualitative and quantitative analyses of post‐infection characteristics such as sporulation and mycotoxin production. Cultivation of A. thaliana seeds under uniform environmental conditions is necessary to limit genotype‐independent seed‐lot variability. Using the A. nidulans oxylipin mutant, ΔppoABC, and two well‐characterized A. thaliana pathogen‐defence mutants, ein2‐1 and pad4‐1, the AAI assay permitted genetic analysis of seed infection and mycotoxin production. Sporulation, but not mycotoxin production, was impaired in A. nidulans ΔppoABC, while A. thaliana ein2‐1 and pad4‐1 had a small but detectable influence on A. nidulans sporulation that appeared to be dependent on seed age.
Widespread transport of pyroclastic density currents from a large silicic tuff ring: the Glaramara tuff, Scafell caldera, English Lake District, UK
Authors: BROWN R. J. , KOKELAAR B. P. , BRANNEY M. J.
Published: June 2007

The Glaramara tuff presents extensive exposures of the medial and distal deposits of a large tuff ring (original area >800 km2) that grew within an alluvial to lacustrine caldera basin. Detailed analysis and correlation of 21 sections through the tuff show that the eruption involved phreatomagmatic to magmatic explosions resulting from the interaction of dacitic magma and shallow‐aquifer water. As the eruption developed to peak intensity, numerous, powerful single‐surge pyroclastic density currents reached beyond 8 km from the vent, probably >12 km. The currents were strongly depletive and deposited coarse lapilli (>5 cm in diameter) up to 5 km from source, with only fine ash and accretionary lapilli deposited beyond this. As the eruption intensity waned, currents deposited fine ash and accretionary lapilli across both distal and medial regions. The simple wax–wane cycle of the eruption produced an overall upward coarsening to fining sequence of the vertical lithofacies succession together with a corresponding progradational to retrogradational succession of lithofacies relative to the vent. Various downcurrent facies transitions record transformations of the depositional flow‐boundary zones as the depletive currents evolved with distance, in some cases transforming from granular fluid‐based to fully dilute currents primarily as a result of loss of granular fluid by deposition. The tuff‐ring deposits share several characteristics with (larger) ignimbrite sheets formed during Plinian eruptions and this underscores some overall similarities between pyroclastic density currents that form tuff rings and those that deposit large‐volume ignimbrites. Tuff‐ring explosive activity with such a wide area of impact is not commonly recognized, but it records the possibility of such currents and this should be factored into hazard assessments.
Lake sediments deposited on the Flims rockslide mass: the key to date the largest mass movement of the Alps
Authors: Deplazes Gaudenz , Anselmetti Flavio S. , Hajdas Irka
Published: June 2007

Long piston cores taken from the subsurface of two mountain lakes of the eastern Swiss Alps recovered sediments, which overlie the Flims rockslide deposits. These sediments provide new information on the chronology of the largest known Alpine rockslide and can be used to reconstruct the post landslide environmental evolution. The oldest 14C date of the lake sediments yields a minimum age of the rockslide at 9660–9430 cal. yr BP. In addition, the dating of a wood fragment contained in the rockslide deposits directly below the lake sediments shows a maximum age of 9480–9120 cal. yr BP. The overlap of the maximum and minimum ages, 9480–9430 cal. yr BP, approximates the age of the Flims rockslide. This early Holocene range coincides with a period of higher frequency of large mass movements observed in the Alps, which could be related to climatic changes.
Illegitimate recombination is a major evolutionary mechanism for initiating size variation in plant resistance genes
Authors: Wicker Thomas , Yahiaoui Nabila , Keller Beat
Published: June 2007

Current models for the evolution of plant disease resistance (R) genes are based on mechanisms such as unequal crossing‐over, gene conversion and point mutations as sources for genetic variability and the generation of new specificities. Size variation in leucine‐rich repeat (LRR) domains was previously mainly attributed to unequal crossing‐over or template slippage between LRR units. Our analysis of 112 R genes and R gene analogs (RGAs) from 16 different gene lineages from monocots and dicots showed that individual LRR units are mostly too divergent to allow unequal crossing‐over. We found that illegitimate recombination (IR) is the major mechanism that generates quasi‐random duplications within the LRR domain. These initial duplications are required as seeds for subsequent unequal crossing‐over events which cause the observed rapid increase or decrease in LRR repeat numbers. Ten of the 16 gene lineages studied contained such duplications, and in four of them the duplications served as a template for subsequent repeat amplification. Our analysis of Pm3‐like genes from rice and three wheat species showed that such events can be traced back more than 50 million years. Thus, IR represents a major new evolutionary mechanism that is essential for the generation of molecular diversity in evolution of RGAs.
The Stagonospora nodorum‐wheat pathosystem involves multiple proteinaceous host‐selective toxins and corresponding host sensitivity genes that interact in an inverse gene‐for‐gene manner
Authors: Friesen Timothy L. , Meinhardt Steven W. , Faris Justin D.
Published: June 2007

We recently showed that the wheat pathogen Stagonospora nodorum produces proteinaceous host‐selective toxins (HSTs). These toxins include SnTox1 as well as SnToxA, a HST first identified from Pyrenophora tritici‐repentis that was implicated in a very recent horizontal gene transfer event from S. nodorum to P. tritici‐repentis. Compelling evidence implicating SnToxA and SnTox1 in disease development has been obtained. Here, we report the partial purification and characterization of a third HST designated SnTox2, as well as the genetic characterization of the corresponding host‐sensitivity gene. SnTox2 was protease sensitive and is estimated between 7 and 10 kDa in size. Sensitivity to SnTox2 was conferred by a single dominant gene designated Snn2, which mapped to the short arm of wheat chromosome 2D. Genetic analysis of reaction to conidial inoculations in a segregating wheat population indicated that both the Snn2‐SnTox2 and the Tsn1‐SnToxA interactions were involved in disease development, and together they accounted for the majority of the phenotypic variation. Therefore, S. nodorum produces multiple toxins that rely on specific interactions with host gene products to cause disease. The identification of multiple HST–host gene interactions important for disease development and the availability of the S. nodorum whole genome sequence indicate the potential for this pathosystem to serve as a toxin‐based, inverse gene‐for‐gene model.