bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between biosynthesis of nitric oxide and changes in immunological and vascular parameters in patients treated with interleukin‐2
Authors: MILES D. , THOMSEN L. , BALKWILL F. , THAVASU P. , MONCADA S. 
Published: March 2008

Abstract Hypotension is a dose‐limiting side effect of interleukin‐2 (IL‐2) therapy. This may be due to increased biosynthesis of the potent vasodilator nitric oxide (NO) induced by cytokines such as tumour necrosis factor‐α (TNF‐α) and interferon‐γ (IFN‐γ), which are known to be generated during IL‐2 therapy. We describe the relationship between NO biosynthesis and changes in immunological and vascular parameters during IL‐2 therapy in 13 patients with metastatic cancer.Plasma concentrations of neopterin and nitrite plus nitrate (NOx) were higher in cancer patients prior to treatment compared with normal subjects (neopterin; 10·8±1·4 vs. 2·0±0·4 ng ml‐1, P<0·001: NOx; 45±6 vs. 28±2 μM, P<0·005). Pretreatment TNF‐α and IFN‐γ plasma concentrations were not significantly different in cancer patients from those in controls. During infusion of IL‐2 (18 times 106 international units m‐2 per day for 5 days) these parameters increased, reaching maximal concentrations at day 3 for IFN‐γ and day 5 for TNF‐α, neopterin and NOx. The maximal induced NOx correlated with maximal TNF‐α (r = 0·60, P<0·04), IFN‐γ (r = 0·63, P<0·02) and neopterin (r = 0·66, P<0·01). As plasma NOx concentrations increased, systolic blood pressure fell, reaching a minimum at day 3 despite a continued rise in NOx concentrations. These changes were accompanied by a continuous increase in pulse rate throughout the infusion period. These findings indicate that induction of NO biosynthesis contributes to hypotension induced during IL‐2 therapy. Inhibitors of NO synthase may be useful in limiting toxicity, thus allowing administration of higher and possibly more efficacious doses of this cytokine in the treatment of cancer.
Neuropeptide Y and energy balance: one way ahead for the treatment of obesity?
Authors: DRYDEN S. , FRANKISH H. , WANG QIONG , WILLIAMS G. 
Published: March 2008

Abstract Obesity is a vast and ever‐expanding problem in affluent societies, which we have so far failed to confront. Over 20% of Western European and North American adults are overweight to a degree which may potentially shorten their life expectancy. Obesity has well‐known associations with non‐insulin‐dependent diabetes (NIDDM), hypertension, dyslipidaemia and coronary heart disease, as well as less obvious links with diseases such as osteoarthrosis and various malignancies; it also causes considerable problems through reduced mobility and decreased quality of life. The overall financial burden of obesity is impossible to calculate precisely, but may account for 6–8% of total health‐care expenditure in North America [1] (similar estimates probably apply to Western Europe).Obesity is difficult to treat and many patients remain obstinately overweight despite our best efforts. The available options range from behavioural therapy to gastrointestinal surgery and include numerous drugs designed to suppress appetite or increase energy expenditure. As in many other areas of medicine, the length and diversity of this list are reliable signs that effective treatment is still beyond our reach.This article argues that new anti‐obesity drugs may emerge from recent advances in understanding the control of energy balance in rodents. The discussion is structured around neuropeptide Y (NPY), a major brain peptide which at present appears to be important in regulating energy balance and seems a promising candidate for therapeutic exploitation.
Local serum application: restoration of sufficient host defense in human peritonitis
Authors: BILLING A. G. , FRÖHLICH D. , KONECNY G. , SCHILDBERG F. W. , MACHLEIDT W. , FRITZ H. , JOCHUM M. 
Published: March 2008

Abstract. Intra‐abdominal host defense in human peritonitis is hampered by a severe dysfunction of phagocytosis due to an almost complete breakdown of bacteria opsonization. This defect relates to some opsonin consumption, but mainly to proteolytic and oxidative opsonin destruction. To restore and protect intact opsonins we have developed a clinical approach of intra‐operative peritoneal serum application. In a prospective, controlled, and randomized study of 30 patients with generalized peritonitis we have investigated the impact of this adjuvant therapy on biochemical parameters and clinical features. Serum application induced a rise in opsonin concentration and, even more pronounced, opsonin function (P < 0·01) of several hours' duration, leading to a distinct improvement of bacteria elimination. In addition, α1‐proteinase inhibitor (α1‐P)I levels were significantly increased after 1 h (P < 0·05) in the treatment group.The follow‐up by APACHE II scoring indicated an improvement in the therapy group over the whole observation period of 14 days. Lethality in the therapy group was 33% compared to 53% in controls. These results indicate that the intra‐operative restoration of physiologic intra‐abdominal milieu can improve bacteria opsonization and elimination, thus contributing to a favourable clinical course in abdominal sepsis.
Vegetation and flow regime in lowland streams
Authors: RIIS TENNA , SUREN ALASTAIR M. , CLAUSEN BENTE , SAND‐JENSEN KAJ 
Published: March 2008

Summary1. The hydrological regime is important to the distribution of benthic organisms in streams. The objective of this study was to identify relationships between hydrological variables, describing the flow regime, and macrophyte cover, species richness, diversity and community composition in Danish lowland streams.2. We quantified macrophyte vegetation in 44 Danish streams during summer by cover, species richness and diversity. Flow regime was characterized by 18 non‐intercorrelated variables describing magnitude, frequency and duration of low and high flow events, timing or predictability of flow and general flow variability.3. We found support in the stepwise multiple regressions analysis for our expectation that macrophyte cover is lowest in streams with high flow variability and highest in streams with long duration of low flow and low flow variability. We found support for the intermediate disturbance hypothesis as there were significant quadratic relationships between species richness and diversity as functions of disturbance frequency. There was poor discrimination in a detrended correspondence analysis (DCA) analysis of macrophyte community composition between four twinspan groups separating streams with different hydrological properties. Moreover, we did not find any relationship between the presence of disturbance‐tolerant species and hydrological disturbance, suggesting that plant community composition developed independently of stream hydrology.
East meets west: adaptive evolution of an insect introduced for biological control
Authors: Phillips C. B , Baird D. B , Iline I. I , McNeill M. R , Proffitt J. R , Goldson S. L , Kean J. M 
Published: March 2008

Summary

A possible explanation for low success rates when introducing natural enemies to new regions for biological control of insect pests is that they fail to adapt to their new conditions. Therefore it has been widely recommended that biological control practitioners increase the probability of local adaptation by maximizing the genetic variation released. An alternative recommendation is to use climate matching to identify native populations that may already possess traits suited to the new region. However, support for these recommendations is weak through lack of empirical evidence that local adaptation is important to biological control.
This study examined how genetic drift and selection influenced the population frequencies of two asexually reproducing, genetically differentiated parasitoid biotypes that were introduced to New Zealand from South America for biological control. Other than by mutation, the biotypes were genetically fixed due to the absence of recombination both within and between biotypes. This meant that adaptive evolution could occur only if selection acted on any traits that varied between the biotypes introduced from South America.
The two parasitoid biotypes were released simultaneously at 14 sites and their frequencies were monitored for up to 10 years. Changes in biotype frequency were consistent with strong directional selection favouring one of the South American biotypes, thus generating established parasitoid populations that were better adapted to New Zealand conditions than those that had originally been released. This local adaptation of the control agent contributed to greater mortality of the pest.
Synthesis and applications. This study provides the first clear demonstration of the importance of releasing natural enemy genetic variation in new regions to foster adaptive evolution and improve success rates in classical biological control. However, the benefit to biological control of maximizing the genetic variation released needs to be balanced against possible risks to non‐target species. The results do not support the concept of choosing sampling sites for putative biological control agents based solely on climatic similarities between the source location and the intended region of introduction.
A novel gene, phcA from Pseudomonas syringae induces programmed cell death in the filamentous fungus Neurospora crassa
Authors: Wichmann Gale , Sun Jianping , Dementhon Karine , Glass N. Louise , Lindow Steven E. 
Published: March 2008

SummaryThe phytopathogen Pseudomonas syringae competes with other epiphytic organisms, such as filamentous fungi, for resources. Here we characterize a gene in P. syringae pv. syringae B728a and P. syringae pv. tomato DC3000, termed phcA, that has homology to a filamentous fungal gene called het‐c. phcA is conserved in many P. syringae strains, but is absent in one of the major clades, which includes the P. syringae pathovar phaseolicola. In the filamentous fungus Neurospora crassa, HET‐C regulates a conserved programmed cell death pathway called heterokaryon incompatibility (HI). Ectopic expression of phcA in N. crassa induced HI and cell death that was dependent on the presence of a functional het‐c pin‐c haplotype. Further, by co‐immunoprecipitation experiments, a heterocomplex between N. crassa HET‐C1 and PhcA was associated with phcA‐induced HI. P. syringae was able to attach and extensively colonize N. crassa hyphae, while an Escherichia coli control showed no association with the fungus. We further show that the P. syringae is able to use N. crassa as a sole nutrient source. Our results suggest that P. syringae has the potential to utilize phcA to acquire nutrients from fungi in nutrient‐limited environments like the phyllosphere by the novel mechanism of HI induction.
An isochromosome confers drug resistance in vivo by amplification of two genes, ERG11 and TAC1
Authors: Selmecki Anna , Gerami‐Nejad Maryam , Paulson Carsten , Forche Anja , Berman Judith 
Published: March 2008

SummaryAcquired azole resistance is a serious clinical problem that is often associated with the appearance of aneuploidy and, in particular, with the formation of an isochromosome [i(5L)] in the fungal opportunist Candida albicans. Here we exploited a series of isolates from an individual patient during the rapid acquisition of fluconazole resistance (FluR). Comparative genome hybridization arrays revealed that the presence of two extra copies of Chr5L, on the isochromosome, conferred increased FluR and that partial truncation of Chr5L reduced FluR. In vitro analysis of the strains by telomere‐mediated truncations and by gene deletion assessed the contribution of all Chr5L genes and of four specific genes. Importantly, ERG11 (encoding the drug target) and a hyperactive allele of TAC1 (encoding a transcriptional regulator of drug efflux pumps) made independent, additive contributions to FluR in a gene copy number‐dependent manner that was not different from the contributions of the entire Chr5L arm. Thus, the major mechanism by which i(5L) formation causes increased azole resistance is by amplifying two genes: ERG11 and TAC1.
TtsI regulates symbiotic genes in Rhizobium species NGR234 by binding to tts boxes
Authors: Wassem Roseli , Kobayashi Hajime , Kambara Kumiko , Le Quéré Antoine , Walker Graham C. , Broughton William J. , Deakin William J. 
Published: March 2008

SummaryInfection of legumes by Rhizobium sp. NGR234 and subsequent development of nitrogen‐fixing nodules are dependent on the coordinated actions of Nod factors, proteins secreted by a type III secretion system (T3SS) and modifications to surface polysaccharides. The production of these signal molecules is dependent on plant flavonoids which trigger a regulatory cascade controlled by the transcriptional activators NodD1, NodD2, SyrM2 and TtsI. TtsI is known to control the genes responsible for T3SS function and synthesis of a symbiotically important rhamnose‐rich lipo‐polysaccharide, most probably by binding to cis elements termed tts boxes. Eleven tts boxes were identified in the promoter regions of target genes on the symbiotic plasmid of NGR234. Expression profiles of lacZ fusions to these tts boxes showed that they are part of a TtsI‐dependent regulon induced by plant‐derived flavonoids. TtsI was purified and demonstrated to bind directly to two of these tts boxes. DNase I footprinting revealed that TtsI occupied not only the tts box consensus sequence, but also upstream and downstream regions in a concentration‐dependent manner. Highly conserved bases of the consensus tts box were mutated and, although TtsI binding was still observed in vitro, gfp fusions were no longer transcribed in vivo. Random mutagenesis of a tts box‐containing promoter revealed more nucleotides critical for transcriptional activity outside of the consensus.
Oxidant‐dependent switching between reversible and sacrificial oxidation pathways for Bacillus subtilis OhrR
Authors: Soonsanga Sumarin , Lee Jin‐Won , Helmann John D. 
Published: March 2008

SummaryThe Bacillus subtilis OhrR protein functions as a transcriptional repressor of the inducible peroxidase, OhrA. Derepression is mediated by the organic‐peroxide selective oxidation of an active site cysteine (C15). In the presence of cumene hydroperoxide (CHP), oxidation of OhrR leads to a sulphenic acid intermediate which reacts to form either a mixed‐disulphide or a protein sulphenamide. These inactive forms of OhrR can be reactivated by thiol–disulphide exchange reactions allowing restoration of repression. Here, we demonstrate that linoleic acid hydroperoxide (LHP) is a potent oxidant for OhrR and even low levels lead to overoxidation of OhrR to cysteine sulphinic (and sulphonic) acid derivatives. Kinetic competition experiments indicate that further oxidation of the initial OhrR sulphenate product occurs at least 100‐fold more rapidly with LHP than with CHP. Thus, depending on the oxidant, OhrR can be either reversibly oxidized or can instead function as a sacrificial regulator.
Mini‐III, an unusual member of the RNase III family of enzymes, catalyses 23S ribosomal RNA maturation in B. subtilis
Authors: Redko Yulia , Bechhofer David H. , Condon Ciarán 
Published: March 2008

SummaryThe late steps of both 16S and 5S ribosomal RNA maturation in the Gram‐positive bacterium Bacillus subtilis have been shown to be catalysed by ribonucleases that are not present in the Gram‐negative paradigm, Escherichia coli. Here we present evidence that final maturation of the 5′ and 3′ extremities of B. subtilis 23S rRNA is also performed by an enzyme that is absent from the Proteobacteria. Mini‐III contains an RNase III‐like catalytic domain, but curiously lacks the double‐stranded RNA binding domain typical of RNase III itself, Dicer, Drosha and other well‐known members of this family of enzymes. Cells lacking Mini‐III accumulate precursors and alternatively matured forms of 23S rRNA. We show that Mini‐III functions much more efficiently on precursor 50S ribosomal subunits than naked pre‐23S rRNA in vitro, suggesting that maturation occurs primarily on assembled subunits in vivo. Lastly, we provide a model for how Mini‐III recognizes and cleaves double‐stranded RNA, despite lacking three of the four RNA binding motifs of RNase III.
Characterization of the PvdS‐regulated promoter motif in Pseudomonas syringae pv. tomato DC3000 reveals regulon members and insights regarding PvdS function in other pseudomonads
Authors: Swingle Bryan , Thete Deepti , Moll Monica , Myers Christopher R. , Schneider David J. , Cartinhour Samuel 
Published: March 2008

SummaryBacteria that survive under variable conditions possess an assortment of genetic regulators to meet these challenges. The group IV or extracytoplasmic function (ECF) sigma factors regulate gene expression in response to specific environmental signals by altering the promoter specificity of RNA polymerase. We have undertaken a study of PvdS, a group IV sigma factor encoded by Pseudomonas syringae pv. tomato DC3000 (DC3000), a plant pathogen that is likely to encounter variations in nutrient availability as well as plant host defences. The gene encoding PvdS was previously identified by sequence similarity to the Pseudomonas aeruginosa orthologue, which directs transcription of genes encoding the biosynthesis of pyoverdine, a siderophore involved in iron acquisition, and is responsible for the characteristic fluorescence of the pseudomonads. We identified 15 promoters regulated by PvdS in DC3000 and characterized the promoter motif using computational analysis. Mutagenesis of conserved nucleotides within the motif interfered with promoter function and the degree of the effect was different depending on which region of the motif was mutated. Hidden Markov models constructed from alignments of sequence motifs extracted from DC3000 and PAO1 were used to query genomes of DC3000 and other fluorescent pseudomonads for similar motifs. We conclude that the role of PvdS as a regulator of pyoverdine synthesis is conserved among the fluorescent pseudomonads, but the promoters recognized by PvdS orthologues may differ subtly from species to species.
Delayed activation of Xer recombination at dif by FtsK during septum assembly in Escherichia coli
Authors: Kennedy Sean P. , Chevalier Fabien , Barre François‐Xavier 
Published: March 2008

SummaryThe co‐ordination and synchronization of DNA replication, chromosome partitioning and cell division in bacteria are critical to survival. In Escherichia coli, the septal protein FtsK links cell division and chromosome segregation through its integral membrane N‐terminal and cytoplasmic C‐terminal domains. FtsK is responsible for promoting decatenation and dimer resolution in the later stages of chromosome segregation by activating recombination at dif by the site‐specific Xer recombinases. Here, we formally demonstrate, using novel assay based on real‐time quantitative polymerase chain reaction, that dif recombination depends not only on proteins upstream of FtsK in the septum assembly pathway, but also on the activity of downstream proteins. Work in synchronized cell cultures further showed that even though FtsK is recruited early to the septum, dif recombination only occurs shortly before cell division and this activity requires a closing septum. We propose a model whereby septum localization and concentration of FtsK co‐ordinate its various roles in chromosome segregation and cell division.
How obligatory is anaerobiosis?
Authors: Imlay James A. 
Published: March 2008

SummaryHistorically many bacteria have been classified as obligate anaerobes. They have been construed as wholly intolerant of oxygen, a feature that was originally ascribed to their lack of superoxide dismutases and catalases. Clostridial species were regarded as classic examples. We now know that this view is quite wrong: enzymes that scavenge superoxide, hydrogen peroxide and even oxygen itself abound in anaerobes. In the current issue of Molecular Microbiology, Hillmann et al. demonstrate that full production of these proteins can allow Clostridium acetobutylicum to survive and even grow in oxygenated culture medium. Evidently, oxidative defences in anaerobes can be robust. In all likelihood, they are critical for the movement of bacteria through aerobic environments to new anaerobic habitats.
Location and architecture of the Caulobacter crescentus chemoreceptor array
Authors: Briegel Ariane , Ding H. Jane , Li Zhuo , Werner John , Gitai Zemer , Dias D. Prabha , Jensen Rasmus B. , Jensen Grant J. 
Published: March 2008

SummaryA new method for recording both fluorescence and cryo‐EM images of small bacterial cells was developed and used to identify chemoreceptor arrays in cryotomograms of intact Caulobacter crescentus cells. We show that in wild‐type cells preserved in a near‐native state, the chemoreceptors are hexagonally packed with a lattice spacing of 12 nm, just a few tens of nanometers away from the flagellar motor that they control. The arrays were always found on the convex side of the cell, further demonstrating that Caulobacter cells maintain dorsal/ventral as well as anterior/posterior asymmetry. Placing the known crystal structure of a trimer of receptor dimers at each vertex of the lattice accounts well for the density and agrees with other constraints. Based on this model for the arrangement of receptors, there are between one and two thousand receptors per array.
A versatile strategy to define the phosphorylation preferences of plant protein kinases and screen for putative substrates
Authors: Vlad Florina , Turk Benjamin E. , Peynot Philippe , Leung Jeffrey , Merlot Sylvain 
Published: March 2008

SummaryMost signaling networks are regulated by reversible protein phosphorylation. The specificity of this regulation depends in part on the capacity of protein kinases to recognize and efficiently phosphorylate particular sequence motifs in their substrates. Sequenced plant genomes potentially encode over than 1000 protein kinases, representing 4% of the proteins, twice the proportion found in humans. This plethora of plant kinases requires the development of high‐throughput strategies to identify their substrates. In this study, we have implemented a semi‐degenerate peptide array screen to define the phosphorylation preferences of four kinases from Arabidopsis thaliana that are representative of the plant calcium‐dependent protein kinase and Snf1‐related kinase superfamily. We converted these quantitative data into position‐specific scoring matrices to identify putative substrates of these kinases in silico in protein sequence databases. Our data show that these kinases display related but nevertheless distinct phosphorylation motif preferences, suggesting that they might share common targets but are likely to have specific substrates. Our analysis also reveals that a conserved motif found in the stress‐related dehydrin protein family may be targeted by the SnRK2‐10 kinase. Our results indicate that semi‐degenerate peptide array screening is a versatile strategy that can be used on numerous plant kinases to facilitate identification of their substrates, and therefore represents a valuable tool to decipher phosphorylation‐regulated signaling networks in plants.