bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitogenetic structure of brown bears (Ursus arctos L.) in northeastern Europe and a new time frame for the formation of European brown bear lineages
Authors: SAARMA URMAS , HO SIMON Y. W. , PYBUS OLIVER G. , KALJUSTE MARJU , TUMANOV IGOR L. , KOJOLA ILPO. , VOROBIEV ALEX A. , MARKOV NIKOLAI I. , SAVELJEV ALEXANDER P. , VALDMANN HARRI , LYAPUNOVA ELENA A. , ABRAMOV ALEXEI V. , MÄNNIL PEEP. , KORSTEN MARJU , VULLA EGLE. , PAZETNOV SERGEI V. , PAZETNOV VALENTIN S. , PUTCHKOVSKIY STANISLAV V. , RÕKOV ALEXANDER M. 
Published: November 2006

AbstractWe estimated the phylogenetic relationships of brown bear maternal haplotypes from countries of northeastern Europe (Estonia, Finland and European Russia), using sequences of mitochondrial DNA (mtDNA) control region of 231 bears. Twenty‐five mtDNA haplotypes were identified. The brown bear population in northeastern Europe can be divided into three haplogroups: one with bears from all three countries, one with bears from Finland and Russia, and the third composed almost exclusively of bears from European Russia. Four haplotypes from Finland and European Russia matched exactly with haplotypes from Slovakia, suggesting the significance of the current territory of Slovakia in ancient demographic processes of brown bears. Based on the results of this study and those from the recent literature, we hypothesize that the West Carpathian Mountains have served either as one of the northernmost refuge areas or as an important movement corridor for brown bears of the Eastern lineage towards northern Europe during or after the last ice age. Bayesian analyses were performed to investigate the temporal framework of brown bear lineages in Europe. The molecular clock was calibrated using Beringian brown bear sequences derived from radiocarbon‐dated ancient samples, and the estimated mutation rate was 29.8% (13.3%−47.6%) per million years. The whole European population and Western and Eastern lineages formed about 175 000, 70 000 and 25 000 years before present, respectively. Our approach to estimating the time frame of brown bear evolution demonstrates the importance of using an appropriate mutation rate, and this has implications for other studies of Pleistocene populations.
Characterization of the OxyR regulon of Neisseria gonorrhoeae
Authors: Seib Kate L. , Wu Hsing‐Ju , Srikhanta Yogitha N. , Edwards Jennifer L. , Falsetta Megan L. , Hamilton Amanda J. , Maguire Tina L. , Grimmond Sean M. , Apicella Michael A. , McEwan Alastair G. , Jennings Michael P. 
Published: November 2006

SummaryOxyR regulates the expression of the majority of H2O2 responses in Gram‐negative organisms. In a previous study we reported the OxyR‐dependent derepression of catalase expression in the human pathogen Neisseria gonorrhoeae. In the present study we used microarray expression profiling of N. gonorrhoeae wild‐type strain 1291 and an oxyR mutant strain to define the OxyR regulon. In addition to katA (encoding catalase), only one other locus displayed a greater than two‐fold difference in expression in the wild type : oxyR comparison. This locus encodes an operon of two genes, a putative peroxiredoxin/glutaredoxin (Prx) and a putative glutathione oxidoreductase (Gor). Mutant strains were constructed in which each of these genes was inactivated. A previous biochemical study in Neisseria meningitidis had confirmed function of the glutaredoxin/peroxiredoxin. Assay of the wild‐type 1291 cell free extract confirmed Gor activity, which was lost in the gor mutant strain. Phenotypic analysis of the prx mutant strain in H2O2 killing assays revealed increased resistance, presumably due to upregulation of alternative defence mechanisms. The oxyR, prx and gor mutant strains were deficient in biofilm formation, and the oxyR and prx strains had decreased survival in cervical epithelial cells, indicating a key role for the OxyR regulon in these processes.
Substitutions in the N‐terminal alpha helical spine of Neisseria gonorrhoeae pilin affect Type IV pilus assembly, dynamics and associated functions
Authors: Aas Finn Erik , Winther‐Larsen Hanne C. , Wolfgang Matthew , Frye Stephan , Løvold Cecilia , Roos Norbert , Van Putten Jos P. M. , Koomey Michael 
Published: November 2006

SummaryType IV pili (Tfp) are multifunctional surface appendages expressed by many Gram negative species of medical, environmental and industrial importance. The N‐terminally localized, so called α‐helical spine is the most conserved structural feature of pilin subunits in these organelles. Prevailing models of pilus assembly and structure invariably implicate its importance to membrane trafficking, organelle structure and related functions. Nonetheless, relatively few studies have examined the effects of missense substitutions within this domain. Using Neisseria gonorrhoeae as a model system, we constructed mutants with single and multiple amino acid substitutions localized to this region of the pilin subunit PilE and characterized them with regard to pilin stability, organelle expression and associated phenotypes. The consequences of simultaneous expression of the mutant and wild‐type PilE forms were also examined. The findings document for the first time in a defined genetic background the phenomenon of pilin intermolecular complementation in which assembly defective pilin can be rescued into purifiable Tfp by coexpression of wild‐type PilE. The results further demonstrate that pilin subunit composition can impact on organelle dynamics mediated by the PilT retraction protein via a process that appears to monitor the efficacy of subunit–subunit interactions. In addition to confirming and extending the evidence for PilE multimerization as an essential component for competence for natural genetic transformation, this work paves the way for detailed studies of Tfp subunit–subunit interactions including self‐recognition within the membrane and packing within the pilus polymer.
A family of stage‐specific alanine‐rich proteins on the surface of epimastigote forms of Trypanosoma brucei
Authors: Urwyler Simon , Studer Erwin , Renggli Christina Kunz , Roditi Isabel 
Published: November 2006

SummaryA ‘two coat’ model of the life cycle of Trypanosoma brucei has prevailed for more than 15 years. Metacyclic forms transmitted by infected tsetse flies and mammalian bloodstream forms are covered by variant surface glycoproteins. All other life cycle stages were believed to have a procyclin coat, until it was shown recently that epimastigote forms in tsetse salivary glands express procyclin mRNAs without translating them. As epimastigote forms cannot be cultured, a procedure was devised to compare the transcriptomes of parasites in different fly tissues. Transcripts encoding a family of glycosylphosphatidyl inositol‐anchored proteins, BARPs (previously called bloodstream alanine‐rich proteins), were 20‐fold more abundant in salivary gland than midgut (procyclic) trypanosomes. Anti‐BARP antisera reacted strongly and exclusively with salivary gland parasites and a BARP 3′ flanking region directed epimastigote‐specific expression of reporter genes in the fly, but inhibited expression in bloodstream and procyclic forms. In contrast to an earlier report, we could not detect BARPs in bloodstream forms. We propose that BARPs form a stage‐specific coat for epimastigote forms and suggest renaming them brucei alanine‐rich proteins.
Clostridium taeniosporum spore ribbon‐like appendage structure, composition and genes
Authors: Walker James R. , Gnanam Annie J. , Blinkova Alexandra L. , Hermandson Mary Jo , Karymov Mikhail A. , Lyubchenko Yuri L. , Graves Paul R. , Haystead Timothy A. , Linse Klaus D. 
Published: November 2006

Summary Clostridium taeniosporum spores have about 12 large, flat, ribbon‐like appendages attached through a common trunk at one spore pole to a previously unknown surface layer outside the coat that is proposed to be called the ‘encasement’. Appendages are about 4.5 μm long, 0.5 μm wide and 30 nm thick and taper at the attachment end into a semicircle that is twisted relative to the flat ribbon. Individual fibrils, about 45 nm in length with spherical heads and long thin tails, form a hair‐like nap, visible along the appendage edge. Four appendage proteins have been detected: a paralogous pair of 29 kDa (designated P29a and P29b), a glycoprotein of about 37 kDa (designated GP85) and an orthologue of the Bacillus spore morphogenetic protein SpoVM. The P29 proteins consist of duplicated regions and each region includes a domain of unknown function 11. The GP85 glycoprotein contains a collagen‐like region. The genes for P29a and b, GP85 and possibly related proteins are closely linked on two small chromosome fragments. Putative σK‐dependent promoters upstream of the P29a and b genes indicate that they likely are expressed late in the mother cell, consistent with their deposition into the layer external to the coat.
Subcellular positioning of the origin region of the Bacillus subtilis chromosome is independent of sequences within oriC, the site of replication initiation, and the replication initiator DnaA
Authors: Berkmen Melanie B. , Grossman Alan D. 
Published: November 2006

SummaryRegions of bacterial chromosomes occupy characteristic locations within the cell. In Bacillus subtilis, the origin of replication, oriC, is located at 0°/360° on the circular chromosome. After duplication, sister 0° regions rapidly move to and then reside near the cell quarters. It has been hypothesized that origin function or oriC sequences contribute to positioning and movement of the 0° region. We found that the position of a given chromosomal region does not depend on initiation of replication from the 0° region. In an oriC mutant strain that replicates from a heterologous origin (oriN) at 257°, the position of both the 0° and 257° regions was similar to that in wild‐type cells. Thus, positioning of chromosomal regions appears to be independent of which region is replicated first. Furthermore, we found that neither oriC sequences nor the replication initiator DnaA is required or sufficient for positioning a region near the cell quarters. A sequence within oriC previously proposed to play a critical role in chromosome positioning and partitioning was found to make little, if any, contribution. We propose that uncharacterized sites outside of oriC are involved in moving and/or maintaining the 0° region near the cell quarters.
Acid pH activation of the PmrA/PmrB two‐component regulatory system of Salmonella enterica
Authors: Perez J. Christian , Groisman Eduardo A. 
Published: November 2006

SummaryAcid pH often triggers changes in gene expression. However, little is known about the identity of the gene products that sense fluctuations in extracytoplasmic pH. The Gram‐negative pathogen Salmonella enterica serovar Typhimurium experiences a number of acidic environments both inside and outside animal hosts. Growth in mild acid (pH 5.8) promotes transcription of genes activated by the response regulator PmrA, but the signalling pathway(s) that mediates this response has thus far remained unexplored. Here we report that this activation requires both PmrA's cognate sensor kinase PmrB, which had been previously shown to respond to Fe3+ and Al3+, and PmrA's post‐translational activator PmrD. Substitution of a conserved histidine or of either one of four conserved glutamic acid residues in the periplasmic domain of PmrB severely decreased or abolished the mild acid‐promoted transcription of PmrA‐activated genes. The PmrA/PmrB system controls lipopolysaccharide modifications mediating resistance to the antibiotic polymyxin B. Wild‐type Salmonella grown at pH 5.8 were > 100 000‐fold more resistant to polymyxin B than organisms grown at pH 7.7. Our results suggest that protonation of the PmrB periplasmic histidine and/or of the glutamic acid residues activate the PmrA protein, and that mild acid promotes cellular changes resulting in polymyxin B resistance.
Immunomodulatory Role of Chloroquine and Pyrimethamine in Plasmodium yoelii 17XL Infected Mice
Authors: Ramos‐Avila A. , Ventura‐Gallegos J. L. , Zentella‐Dehesa A. , Machuca‐Rodríguez C. , Moreno‐Altamirano M. M. , Narváez V. , Legorreta‐Herrera M. 
Published: November 2006

AbstractChloroquine (CLQ) and Pyrimethamine (PYR) are used for the treatment of malaria and some autoimmune diseases; although their mechanism of action is only partially understood, their therapeutic effectiveness in the second case has been attributed to their ability to increase apoptosis of T lymphocytes. In view of the potential for immunomodulation during malaria chemotherapy, we investigated the effects of CLQ and PYR treatment on lymphocyte apoptosis and cytokine expression during infection with blood‐stage Plasmodium. This work shows that infection of BALB/c mice with Plasmodium yoelii 17XL (Py17XL) reduced apoptosis in spleen cells but when infected mice were treated with CLQ, apoptosis of B and T lymphocytes increased significantly via a Fas‐mRNA expression independent mechanism associated with downregulation of Bcl‐2 expression, whereas treatment with PYR increased apoptosis to a lesser extent and only in B lymphocytes. CLQ treatment of Py17XL infected mice upregulated tumour necrosis factor‐α mRNA expression, while PYR treatment increased interferon‐γ mRNA expression. In infected mice, treatment with CLQ downregulated expression of the anti‐inflammatory cytokines, interleukin‐10 and transforming growth factor‐β (TGF‐β), while PYR treatment upregulated TGF‐β. Thus, in addition to their anti‐malarial effects, both drugs modulate the immune response in malaria by increasing apoptosis and modulating the mRNA expression of cytokines involved in parasite elimination and regulation of inflammatory responses.
Autoantibody‐mediated Bladder Dysfunction in Type 1 Diabetes
Authors: Wan E.‐C. , Gordon T. P. , Jackson M. W. 
Published: November 2006

AbstractBladder dysfunction is a common complication of diabetic autonomic neuropathy; however, its cause remains uncertain. We have recently identified a novel IgG autoantibody (Ab) in patients with type 1 diabetes that acts as an agonist at the dihydropyridine (DHP) site of L‐type voltage‐gated calcium channels (VGCC), disrupting neuronal regulation of visceral smooth muscle. In the present study, passive transfer to mice of IgG from patients with type 1 diabetes was used to investigate the role of anti‐VGCC Abs in mediating diabetic bladder dysfunction. Injection of mice with diabetic immunoglobulin (IgG) with anti‐VGCC activity induced features of an overactive bladder, including phasic detrusor contractions and a loss of bladder wall compliance. The bladder overactivity is mimicked by the DHP agonist Bay K8644, reversed by the DHP antagonist nicardipine, but is insensitive to the motor nerve blocker tetrodotoxin, indicating that the anti‐VGCC Ab acts at the level of the bladder detrusor itself. This study reports the first evidence of Ab‐mediated bladder dysfunction in type 1 diabetes, which may be part of a wider spectrum of smooth muscle and cardiac abnormalities.
Control of FWA gene silencing in Arabidopsis thaliana by SINE‐related direct repeats
Authors: Kinoshita Yuki , Saze Hidetoshi , Kinoshita Tetsu , Miura Asuka , Soppe Wim J.J. , Koornneef Maarten , Kakutani Tetsuji 
Published: November 2006

SummaryA unique feature of late‐flowering fwa epigenetic mutations is that the phenotype is caused by ectopic expression of the homeobox gene FWA. During normal development the FWA gene is expressed specifically in the endosperm in an imprinted manner. Ectopic FWA expression and disruption of imprinting can be induced in mutants of a CG methyltransferase MET1 (methyltransferase 1) or a chromatin‐remodeling gene DDM1 (decrease in DNA methylation 1), suggesting that the proper FWA expression depends on cytosine methylation. However, critical methylated residues controlling FWA silencing are not pinpointed. Nor is it understood how the FWA gene is initially methylated and silenced in wild‐type plants. Here we mapped sequences critical for FWA silencing by application of RdDM (RNA‐directed DNA methylation) to a ddm1‐induced stable fwa epiallele. Transcription of double‐stranded RNA corresponding to the tandem direct repeats around the FWA transcription start site induced de novo DNA methylation, transcriptional suppression and phenotypic reversion. The induced changes were heritable even without the transgene, which correlates with inheritance of CG methylation in the direct repeats. The newly silenced FWA allele was transcribed in an endosperm‐specific and imprinted manner, as is the case for the wild‐type FWA gene. The results indicate that methylation of the direct repeats, which presumably originated from a short interspersed nuclear element (SINE), is sufficient to induce proper epigenetic control of the FWA gene.
The rice heterochronic gene SUPERNUMERARY BRACT regulates the transition from spikelet meristem to floral meristem
Authors: Lee Dong‐Yeon , Lee Jinwon , Moon Sunok , Park Soung Young , An Gynheung 
Published: November 2006

SummaryRegulating the transition of meristem identity is a critical step in reproductive development. After the shoot apical meristem (SAM) acquires inflorescence meristem identity, it goes through a sequential transition to second‐ and higher‐order meristems that can eventually give rise to floral organs. Despite ample information on the molecular mechanisms that control the transition from SAM to inflorescence meristems, little is known about the mechanism for inflorescence development, especially in monocots. Here, we report the identification of the SUPERNUMERARY BRACT (SNB) gene controlling the transition from spikelet meristem to floral meristem and the floral organ development. This gene encodes a putative transcription factor carrying two AP2 domains. The SNB:GFP fusion protein is localized to the nucleus. SNB is expressed in all the examined tissues, but most strongly in the newly emerging spikelet meristems. In SNB knockout plants, the transition from spikelet meristems to floral meristems is delayed, resulting in the production of multiple rudimentary glumes in an alternative phyllotaxy. The development of additional bracts interferes with subsequent floral architecture. In some spikelets, the empty glumes and lodicules are transformed into lemma/palea‐like organs. Occasionally, the number of stamens and carpels is altered and an ectopic floret occurs in the axil of the rachilla. These phenotypes suggest that snb is a heterochronic mutant, affecting the phase transition of spikelet meristems, the pattern formation of floral organs and spikelet meristem determinancy.
Bacterial risk reduction by improved donor arm disinfection, diversion and bacterial screening
Authors: McDonald C. P. 
Published: November 2006

summary The Interventions of improved donor arm disinfection, diversion and bacterial screening have been implemented by blood services and shown to have substantial benefit. The major source of bacterial contamination is donor arm derived. Blood services are now introducing best practice donor arm disinfection techniques.Diversion has been shown to substantially reduce bacterial contamination in the order of 40–88%. Diversion, together with improved donor arm disinfection, has shown to improve the percentage of reduction in contamination from 47% to 77%. Residual contamination levels after the Introduction of diversion and improved donor arm disinfection may be in the order of 30–40%. Numerous countries have now implemented screen testing programmes for platelet concentrates, which are the major source of bacterial transfusion transmission.Pathogen reduction systems have been developed and are under development. At present, concerns remain with these systems regarding cost, process control, ability to inactivate high titres of viruses, killing of bacterial spores, product damage, genotoxicity and mutagenicity.The interventions of diversion, improved donor arm disinfection and bacterial screen testing are currently available, As such they can be implemented now to increase blood safety with no associated patient risk.
Revaccination with Bacillus Calmette‐Guerin (BCG) vaccine does not reduce morbidity from malaria in African children
Authors: Rodrigues Amabelia , Schellenberg Joanna Armstrong , Roth Adam , Benn Christine Stabell , Aaby Peter , Greenwood Brian 
Published: November 2006

SummaryBackground  Studies in West Africa and elsewhere have suggested that Bacillus Calmette‐Guérin (BCG) vaccine given at birth is beneficial for child survival. It is possible that this effect is mediated partly through an effect on malaria, a hypothesis supported by animal studies. We investigated whether revaccination with BCG at 19 months of age reduced morbidity from malaria.Method  In the capital of Guinea‐Bissau, between January and November 2003, children who had previously received BCG vaccination and who did not have a strong reaction to tuberculin were individually randomised to either receive revaccination with BCG at the age of 19 months or to be a control. Episodes of malaria were recorded during the 2003 malaria transmission season through passive case detection at health centres in the study area and at the national hospital. Cross‐sectional surveys were carried out at the beginning and at the end of the rainy season.Results  Incidence rates of first episodes of malaria associated with any level of parasitaemia were 0.16 episodes per child‐year among 713 revaccinated children and 0.12 among 720 control children [incidence rate ratio (IRR) = 1.37; 95% confidence intervals (CI): 0.84–2.25]. Results were similar when the diagnosis of malaria was based on the presence of parasitaemia >5000 parasites/μl (IRR = 1.30; 95% CI: 0.61–2.77). The incidence of all‐cause hospitalisation was higher among BCG‐revaccinated children than among controls (IRR = 2.13; 95% CI: 1.10–4.13). There were no significant differences in the prevalence of parasitaemia between the two groups of children at cross‐sectional surveys.Conclusion  We found no evidence that BCG revaccination reduces morbidity from malaria.
Quality control of active ingredients in artemisinin‐derivative antimalarials within Kenya and DR Congo
Authors: Atemnkeng Magnus A. , De Cock Katelijne , Plaizier‐Vercammen Jacqueline 
Published: November 2006

SummaryObjectives  Artemisinin‐derivative drugs are widely used to treat Plasmodium falciparum malaria and very few studies have investigated the quality of these medicines in Africa. We analysed the active ingredient contents of artemisinin‐derivative drugs marketed in Kenya and DR Congo.Methods  We analysed tablets, capsules, dry suspensions and injections (IM) containing either artemether (AM), arteether (AE), artesunate (ARS) or dihydroartemisinin (DHA). The content of active ingredients and preservatives was determined quantitatively using validated HPLC‐UV methods. All analyses were done according to European pharmacopoeia requirements.Results  Labelled active ingredients were identified in all samples, however with varying dosages. Nine of the 24 drug samples analysed did not comply with the pharmacopoeial requirements of 95–105%: seven samples were underdosed and two were slightly overdosed. DHA was the active ingredient in 57% of the underdosed samples. AE injections had the lowest drug content (77%). Two‐thirds of the dry powder suspensions were either substandard or fake. Tablets were up to 23% out of range. Unidentified peaks were observed on the chromatograms of AE IM injections and a DHA dry powder.Conclusions  Counterfeit or substandard artemisinin‐derivative drugs are being sold in parts of Africa, presenting a potential route for resistance development in the future. Appropriate measures need to be taken to maintain proper and safe use of these medicines.