bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phylogeography of theBothrops jararacacomplex (Serpentes: Viperidae): past fragmentation and island colonization in the Brazilian Atlantic Forest
Authors: GRAZZIOTIN FELIPE G. , MONZEL MARKUS , ECHEVERRIGARAY SERGIO , BONATTO SANDRO L. 
Published: September 2006

AbstractThe Brazilian Atlantic Forest is one of the world's major biodiversity hotspots and is threatened by a severe habitat loss. Yet little is known about the processes that originated its remarkable richness of endemic species. Here we present results of a large‐scale survey of the genetic variation at the mitochondrial cytochromebgene of the pitviper, jararaca lancehead (Bothrops jararaca), and two closely related insular species (Bothrops insularisandBothrops alcatraz), endemic of this region. Phylogenetic and network analyses revealed the existence of two well‐supported clades, exhibiting a southern and a northern distribution. The divergence time of these two phylogroups was estimated at 3.8 million years ago, in the Pliocene, a period of intense climatic changes and frequent fragmentation of the tropical rainforest. Our data also suggest that the two groups underwent a large size expansion between 50 000 and 100 000 years ago. However, the southern group showed a more marked signal of population size fluctuation than the northern group, corroborating evidences that southern forests may have suffered a more pronounced reduction in area in the late Pleistocene. The insular speciesB. alcatrazandB. insularispresented very low diversity, each one sharing haplotypes with mainland individuals placed in different subclades. Despite their marked morphological and behavioural uniqueness, these two insular species seem to have originated very recently and most likely from distinct costalB. jararacapopulations, possibly associated with late Pleistocene or Holocene sea level fluctuations.
Genetic evidence for kin aggregation in the intertidal acorn barnacle (Semibalanus balanoides)
Authors: VELIZ DAVID , DUCHESNE PIERRE , BOURGET EDWIN , BERNATCHEZ LOUIS 
Published: September 2006

AbstractIt is generally assumed that larvae of benthic species are thoroughly mixed in the plankton and distributed randomly at settlement. Yet, it has also been hypothesized that a combination of larval gregarious behaviour coupled with particular oceanographic conditions may prevent larvae from mixing completely, and result in nonrandom spatial distributions following settlement. Using microsatellite markers, the main objective of this study was to investigate the occurrence of statistical connections between relatedness and settlement in the intertidal acorn barnacle from the Gulf of St Lawrence, Canada. A second objective was to test the hypothesis that patches of kin‐related individuals came from a common parental site. Our results indicated that a significant number of barnacles within a given sample were more closely related than expected by chance despite the enormous potential for admixture during the planktonic phase. Thus, eight out of 37 samples analysed had relatedness values significantly higher than expected from random settlement. Moreover, analyses of sibship network construction and network complexity tests provided evidence for the occurrence of networks within several samples that were characterized by strong connections among individuals. Thus, nonrandom planktonic dispersal associated with relatively stable oceanic currents, as well as additional ecological factors to be rigorously investigated (e.g. behavioural mechanisms), may be more important in determining patterns of genetic structure in marine benthic invertebrates than generally assumed. Therefore, documenting genetic patterns associated with kin aggregation should be a fruitful and an important avenue for future studies in marine invertebrates.
Cell wall‐inhibitory antibiotics activate the alginate biosynthesis operon in Pseudomonas aeruginosa: roles of σ22 (AlgT) and the AlgW and Prc proteases
Authors: Wood Lynn F. , Leech Andrew J. , Ohman Dennis E. 
Published: September 2006

SummaryA bioassay was developed to identify stimuli that promote the transcriptional induction of the algD operon for alginate biosynthesis in Pseudomonas aeruginosa. Strain PAO1 carried the algD promoter fused to a chloramphenicol acetyl‐transferase cartridge (PalgD‐cat), and > 50 compounds were tested for promoting chloramphenicol resistance. Most compounds showing PalgD‐cat induction were cell wall‐active antibiotics that blocked peptidoglycan synthesis. PalgD‐cat induction was blocked by mutations in the genes for σ22 (algT/algU) or regulators AlgB and AlgR. Anti‐sigma factor MucA was the primary regulator of σ22 activity. A transcriptome analysis using microarrays verified that the algD operon undergoes high induction by d‐cycloserine. A similar σE–RseAB complex in Escherichia coli responds to envelope stress, which requires DegS protease in a regulated intramembrane proteolysis (RIP) cascade to derepress the sigma. Mutant phenotypic studies in P. aeruginosa showed that AlgW (PA4446) is likely to be the DegS functional homologue. A mutation in algW resulted in a complete lack of PalgD‐cat induction by d‐cycloserine. Overexpression of algW in PAO1 resulted in a mucoid phenotype and alginate production, even in the absence of cell wall stress, suggesting that AlgW protease plays a role in σ22 activation. In addition, a mutation in gene PA3257 (prc), encoding a Prc‐like protease, resulted in poor induction of PalgD‐cat by d‐cycloserine, suggesting that it also plays a role in the response to cell wall stress.
The carrier Msn5p/Kap142p promotes nuclear export of the hsp70 Ssa4p and relocates in response to stress
Authors: Quan XinXin , Tsoulos Panagiotis , Kuritzky Alexandra , Zhang Rui , Stochaj Ursula 
Published: September 2006

SummaryCytoplasmic hsp70s like yeast Ssa4p shuttle between nucleus and cytoplasm under normal growth conditions but accumulate in nuclei upon stress. This nuclear accumulation is only transient, and Ssa4p relocates to the cytoplasm when cells recover. We show here that Ssa4p nuclear export is independent of Xpol/Crm1 and identify the importin‐β family member Msn5p/Kap142p as the exporter for Ssa4p. In growing cells and in vitro, Msn5p and Ssa4p generate genuine export complexes that require Ran/Gsp1p‐GTP. Furthermore, nucleoporin Nup82p, which plays a role in Msn5p‐mediated transport, is necessary for efficient export of Ssa4p. In living cells, stress not only regulates Ssa4p localization, but also controls the distribution of Msn5p. Msn5p is concentrated in nuclei of unstressed cells, but appears in the cytoplasm upon exposure to ethanol, heat, starvation or severe oxidative stress. In addition, growth on non‐fermentable carbon sources relocates a portion of Msn5p to the cytoplasm and leads to a partial nuclear accumulation of Ssa4p. Taken together, growth and stress conditions that localize the transporter Msn5p to the cytoplasm also induce the nuclear accumulation of its cargo Ssa4p.
Heterochromatin‐mediated control of virulence gene expression
Authors: Merrick Catherine J. , Duraisingh Manoj T. 
Published: September 2006

SummaryIn recent years, the sequencing and annotation of complete genomes, together with the development of genetic and proteomic techniques to study previously intractable eukaryotic microbes, has revealed interesting new themes in the control of virulence gene expression. Families of variantly expressed genes are found adjacent to telomeres in the genomes of both pathogenic and non‐pathogenic organisms. This subtelomeric DNA is normally heterochromatic and higher‐order chromatin structure has now come to be recognized as an important factor controlling both the evolution and expression dynamics of these multigene families. In eukaryotic cells, higher‐order chromatin structure plays a central role in many DNA processes including the control of chromosome integrity and recombination, DNA partitioning during cell division, and transcriptional control. DNA can be packaged in two distinct forms: euchromatin is relatively accessible to DNA binding proteins and generally contains active genes, while heterochromatin is densely packaged, relatively inaccessible and usually transcriptionally silent. These features of chromatin are epigenetically inherited from cell cycle to cell cycle. This review will focus on the epigenetic mechanisms used to control expression of virulence genes in medically important microbial pathogens. Examples of such control have now been reported in several evolutionarily distant species, revealing what may be a common strategy used to regulate many very different families of genes.
Complete alanine scanning of the two‐component lantibiotic lacticin 3147: generating a blueprint for rational drug design
Authors: Cotter Paul D. , Deegan Lucy H. , Lawton Elaine M. , Draper Lorraine A. , O'Connor Paula M. , Hill Colin , Ross R. Paul 
Published: September 2006

SummaryLantibiotics are post‐translationally modified antimicrobial peptides which are active at nanomolar concentrations. Some lantibiotics have been shown to function by targeting lipid II, the essential precursor of cell wall biosynthesis. Given that lantibiotics are ribosomally synthesized and amenable to site‐directed mutagenesis, they have the potential to serve as biological templates for the production of novel peptides with improved functionalities. However, if a rational approach to novel lantibiotic design is to be adopted, an appreciation of the roles of each individual amino acid (and each domain) is required. To date no lantibiotic has been subjected to such rigorous analysis. To address this issue we have carried out complete scanning mutagenesis of each of the 59 amino acids in lacticin 3147, a two‐component lantibiotic which acts through the synergistic activity of the peptides LtnA1 (30 amino acids) and LtnA2 (29 amino acids). All mutations were performed in situ in the native 60kb plasmid, pMRC01. A number of mutations resulted in the elimination of detectable bioactivity and seem to represent an invariable core within these and related peptides. Significantly however, of the 59 amino acids, at least 36 can be changed without resulting in a complete loss of activity. Many of these are clustered to form variable domains within the peptides. The information generated in this study represents a blue‐print that will be critical for the rational design of lantibiotic‐based antimicrobial compounds.
A novel oxalosuccinate‐forming enzyme involved in the reductive carboxylation of 2‐oxoglutarate in Hydrogenobacter thermophilus TK‐6
Authors: Aoshima Miho , Igarashi Yasuo 
Published: September 2006

SummaryWe have previously demonstrated that the reductive carboxylation of 2‐oxoglutarate in Hydrogenobacter thermophilus TK‐6 is not simply a reversal of the oxidative decarboxylation catalysed by isocitrate dehydrogenase (ICDH). The reaction involves a novel biotin protein (carboxylating factor for ICDH – CFI) and ATP. In this study, we have analysed the ICDH/CFI system responsible for the carboxylation reaction. Sequence analysis revealed a close relationship between CFI and pyruvate carboxylase. Rather unexpectedly, the rate of ATP hydrolysis was greater than that of isocitrate formation or NADH oxidation. Furthermore, ATP hydrolysis catalysed by CFI was dependent on 2‐oxoglutarate but not on ICDH, suggesting that a carboxylated product is formed in the absence of ICDH. The product, which was detectable only at low temperatures, was identified as oxalosuccinate. Thus, CFI was confirmed to be a novel enzyme that catalyses the carboxylation of 2‐oxoglutarate to form oxalosuccinate, which corresponds to the first step of the reductive carboxylation from 2‐oxoglutarate to isocitrate. The CFI‐ICDH system may also be present in mammals, where it could play a significant role in modulating central metabolism.
nilR is necessary for co‐ordinate repression of Xenorhabdus nematophila mutualism genes
Authors: Cowles Charles E. , Goodrich‐Blair Heidi 
Published: September 2006

SummaryThe bacterial mutualist Xenorhabdus nematophila colonizes a specific region of its nematode host Steinernema carpocapsae. We previously reported the identification of a chromosomal locus encoding three X. nematophila genes of unknown function, nilA, B and C, that are each necessary for colonization. Subsequent work indicated the global regulator Lrp is a repressor of nilC: nilC transcription is elevated in an lrp mutant and Lrp interacts directly with the nilC promoter. In this manuscript, we report the identification of an additional gene, nilR, required for repression of nilC transcription. We show that nilR and lrp mutants also have elevated expression of nilA and nilB, demonstrating that nilA, B and C are co‐ordinately regulated. nil gene expression is derepressed most strongly when both nilR and lrp are lacking, suggesting NilR and Lrp synergistically repress nil transcription. NilR contains a helix–turn–helix‐type DNA binding domain and likely acts directly at promoters. A comparison of the wild type and nilR proteomes indicates that NilR, unlike Lrp, regulates a small number of genes. Finally, X. nematophila carrying an ectopic copy of nilR colonizes at ∼60‐fold lower levels than the control strain, suggesting that derepression of nil gene expression is necessary for nematode colonization.
A specific secretion system mediates PPE41 transport in pathogenic mycobacteria
Authors: Abdallah Abdallah M. , Verboom Theo , Hannes Fredericke , Safi Mohamad , Strong Michael , Eisenberg David , Musters René J. P. , Vandenbroucke‐Grauls Christina M. J. E. , Appelmelk Ben J. , Luirink Joen , Bitter Wilbert 
Published: September 2006

SummaryMycobacterial genomes contain two unique gene families, the so‐called PE and PPE gene families, which are highly expanded in the pathogenic members of this genus. Here we report that one of the PPE proteins, i.e. PPE41, is secreted by pathogenic mycobacteria, both in culture and in infected macrophages. As PPE41 lacks a signal sequence a dedicated secretion system must be involved. A single gene was identified in Mycobacterium marinum that showed strongly reduced PPE41 secretion. This gene was located in a gene cluster whose predicted proteins encode components of an ESAT‐6‐like secretion system. This cluster, designated ESX‐5, is conserved in various pathogenic mycobacteria, but not in the saprophytic species Mycobacterium smegmatis. Therefore, different regions of this cluster were introduced in M. smegmatis. Only introduction of the complete ESX‐5 locus resulted in efficient secretion of heterologously expressed PPE41. This PPE secretion system is also involved in the virulence of pathogenic mycobacteria, as the ESX‐5 mutant of M. marinum was affected in spreading to uninfected macrophages.
Using system analysis to build a safety culture: improving the reliability of epidural analgesia
Authors: Garnerin P. , Huchet‐Belouard A. , Diby M. , Clergue F. 
Published: September 2006

Background:  A potentially dangerous situation was revealed by an incident report describing the use of an inappropriate device to administer post‐operative epidural analgesia to a patient on a surgical ward. The incident occurred in a 1200‐bed university affiliated tertiary hospital (Geneva University Hospitals, HUG) and involved three clinical departments: anaesthesiology, the surgical intensive care unit and urology.Methods:  A multidisciplinary system analysis was carried out to identify care‐delivery problems and contributory factors. Corrective actions were devised on the basis of their ability to prevent and absorb unsafe situations.Results:  The system analysis identified three care‐delivery problems in relation to the management of epidural analgesia. It enabled medical and nursing managers to adopt an interdepartmental set of corrective actions: a common protocol for post‐operative epidural analgesia, leading to the exclusive use of patient‐controlled epidural analgesia (PCEA) pumps; greater availability of the patient‐controlled pumps; the dissemination of guidelines; permanent proactive training of nurses by the acute‐pain team; the clarification of medical responsibilities; and a common help‐line phone number for all surgical departments.Discussion:  The analysis provided a convincing exposure of various care‐delivery problems and their corresponding contributory factors, as well as an opportunity to address a systemic issue in a multidisciplinary way. By thus facilitating decisions and corrective actions, the analysis was instrumental in strengthening our safety culture.
A case of anaphylactic shock possibly caused by intravesical Hexvix®
Authors: Colapaoli L. , Thorsen J. , Nopp A. , Guttormsen A. B. 
Published: September 2006

Background:  We report a case of a 69‐year‐old Caucasian male who experienced a severe drop in blood pressure and a skin rash after fluorescence cystoscopy and transurethral resection of the prostate. The diagnostic agent used for fluorescence cystoscopy and suspected of causing the anaphylaxis was hexaminolevulinate hydrochloride (Hexvix®).Incident:  A profound fall in blood pressure associated with atrial fibrillation, the appearance of a rash, vomiting and transient loss of consciousness occurred immediately after surgery. The hypotension persisted for several hours despite intensive treatment. The reaction commenced approximately 5 h after exposure to Hexvix®. There was an increase in serum tryptase (almost nine‐fold) and a positive skin prick test to undiluted Hexvix®.Conclusion:  The mechanism of the anaphylaxis is uncertain, but is considered likely to be a non‐immunoglobulin E‐mediated allergic reaction possibly caused by Hexvix®. This is the first reported case of a severe allergic reaction after intravesical instillation of Hexvix®.
A single‐model solution for volume kinetic analysis of isotonic fluid infusions
Authors: Drobin D. 
Published: September 2006

Background:  Volume kinetics was developed to analyze the distribution and elimination of intravenously given fluid. However, when groups of patients are being compared, the current approach is limited by the need for several models, which yield parameters that cannot be compared. To meet the requirement to handle all patients in a group individually and without pooling, a new all‐encompassing model was designed. The aim of this paper was to test whether the new model could be used to analyze all patients in a group.Methods:  The new model consists of ‘rate’ and ‘amount’ parameters instead of ‘clearance’ and ‘dilution’ parameters. With this change, a redundant parameter can be taken out, but the biexponential nature is retained. The new parameters are the volume of distribution V1 (ml), the intercompartmental rate constant kt (/min) and the elimination rate constant kr (/min). The success rates of the new and original models in producing results within a set of pre‐determined quality requirements were compared using blood dilution data from 10 volunteers challenged with intravenous lactated Ringer’s solution.Results:  The new model could be used to analyze all 10 cases within the pre‐determined criteria, but the original biexponential model failed in 70% of cases. The residuals improved with the new model. The medians (interquartile ranges) were as follows: V1, 4931 ml (4239–6149 ml); kt, 0.0384/min (0.0024–0.1140/min); kr, 0.0140/min (0.0015–0.0043/min).Conclusion:  The new model was suited to the analysis of all cases, and is therefore a better approach to study how clinical conditions change the distribution and elimination of infused fluid.
Agreement between PiCCO pulse‐contour analysis, pulmonal artery thermodilution and transthoracic thermodilution during off‐pump coronary artery by‐pass surgery
Authors: Halvorsen P. S. , Espinoza A. , Lundblad R. , Cvancarova M. , Hol P. K. , Fosse E. , Tønnessen T. I. 
Published: September 2006

Background:  Haemodynamic instability during off‐pump coronary artery bypass surgery (OPCAB) may appear rapidly, and continuous monitoring of the cardiac index (CI) during the procedure is advisable. With the PiCCO monitor, CI can be measured continuously and almost real time with pulse‐contour analysis and intermittently with transthoracic thermodilution. The agreement between pulmonal artery thermodilution CI (Tpa), transthoracic thermodilution CI (Tpc) and pulse‐contour CI (PCCI) during OPCAB surgery has not been evaluated sufficiently.Methods:  In 30 patients scheduled for OPCAB surgery, a pulmonary artery catheter and a PiCCO catheter were inserted. At different time points during surgery, Tpa, Tpc and PCCI were compared. Measurements were performed after induction of anesthesia (T1), after pericardiothomy (T2), after grafting on the anterior (T3), posterior (T4) and lateral (T5) walls and after chest closure (T6). The PCCI was recalibrated at time point T2–T6.Results:  Mean difference and the limits of agreements (percentage error) between Tpa and Tpc were: –0.14 ± 0.60 (22.0%) l/min/m2, between Tpa and PCCI: –0.07 ± 0.92 (33.5%) l/min/m2 and between Tpc and PCCI: 0.10 ± 1.00 (35.5%) l/min/m2. For changes in CI from one time point to the next (ΔCI), the limits of agreements between ΔCI Tpa and ΔCI Tpc were 0.04 ± 0.90 l/min/m2, between ΔCI Tpa and ΔCI PCCI: –0.02 ± 1.22 l/min/m2 and between ΔCI Tpc and ΔCI PCCI: –0.08 ± 1.32 l/min/m2.Conclusion:  In OPCAB surgery, limits of agreement comparing thermodilution methods were smaller than comparing PCCI with thermodilution. Recalibration of PCCI is therefore advisable.
Propofol inhibits phorbol 12, 13‐dibutyrate‐induced, protein kinase C‐mediated contraction of rat aortic smooth muscle
Authors: Yu J. , Kakutani T. , Mizumoto K. , Hasegawa A. , Hatano Y. 
Published: September 2006

Background: Propofol induces dose‐dependent vasodilation and hypotension in the clinical situation, and protein kinase C (PKC)‐mediated Ca2+sensitization plays an important role in vascular smooth muscle contraction. This study is designed to examine the effects of propofol on the active phorbol ester (phorbol 12, 13‐dibutyrate; PDBu)‐induced, PKC‐mediated contraction of rat aortic smooth muscle.Methods: The PDBu‐induced contraction of endothelium‐denuded rat aortic rings was measured in the presence or absence of PKC inhibitor, bisindolylmaleimide I, or propofol, using isometric force transducers. The PDBu‐induced PKC phosphorylation of endothelium‐denuded rat aortic strips was detected in the presence or absence of bisindolylmaleimide I or propofol, using Western blotting.Results: PDBu, but not the inactive phorbol ester, 4‐α‐phorbol 12‐myristate‐13‐acetate, dose‐dependently induced both a slowly developing sustained contraction and PKC phosphorylation of rat aortic smooth muscle, reaching the peak level at the concentration of 10−6M. The PDBu (10−6M)‐induced contraction was dose‐dependently inhibited by bisindolylmaleimide I with reductions of 6.8 ± 1.8% (P> 0.05), 39.8 ± 8.7% (P< 0.01) and 96.7 ± 1.4% (P< 0.01) in response to concentrations of 5 × 10−7M, 10−6× M and 5 × 10−6M, respectively, and by propofol with decreases of 5.2 ± 1. 6% (P> 0.05), 9.4 ± 1.7% (P< 0.05), 65.3 ± 9.2% (P< 0.01) and 96.2 ± 1.6% (P< 0.01) in response to concentrations of 5 × 10−7M, 10−6M, 5 × 10−6M and 10−5M, respectively. Both bisindolylmaleimide I and propofol also inhibited the PDBu‐induced increase in the density of the phosphorylated PKC bands in a dose‐dependent manner, with decreases of 6.3 ± 2.8% (P> 0.05), 42.9 ± 3.2% (P< 0.01) and 96.6 ± 3.4% (P< 0.01) in response to 5 × 10−7M, 10−6M or 5 × 10−6M bisindolylmaleimide I, respectively, and with decreases of 4.2 ± 2.5% (P> 0.05), 13.5 ± 1.7% (P< 0.05), 69.5 ± 3.5% (P< 0.01) and 95.3 ± 4.3% (P< 0.01) in response to 5 × 10−7M, 10−6M, 5 × 10−6M and 10−5M propofol, respectively.Conclusion: Propofol dose‐dependently inhibits PDBu‐induced, PKC‐mediated contraction of rat aortic smooth muscle.