bluuebunny/crossref_metadata_2025_split huggingface dataset:
The
bkdR
Gene of
Streptomyces coelicolor
Is Required for Morphogenesis and Antibiotic Production and Encodes a Transcriptional Regulator of a Branched-Chain Amino Acid Dehydrogenase Complex
Authors: Sprusansky Ondrej , Stirrett Karen , Skinner Deborah , Denoya Claudio , Westpheling Janet 
Published: January 2005

ABSTRACT

Products from the degradation of the branched-chain amino acids valine, leucine, and isoleucine contribute to the production of a number of important cellular metabolites, including branched-chain fatty acids, ATP and other energy production, cell-cell signaling for morphological development, and the synthesis of precursors for polyketide antibiotics. The first nonreversible reactions in the degradation of all three amino acids are catalyzed by the same branched-chain α-keto acid dehydrogenase (BCDH) complex. Actinomycetes are apparently unique among bacteria in that they contain two separate gene clusters, each of which encodes a BCDH enzyme complex. Here, we show that one of these clusters in
Streptomyces coelicolor
is regulated, at least in part, at the level of transcription by the product of the
bkdR
gene. The predicted product of this gene is a protein with similarity to a family of proteins that respond to leucine and serve to activate transcription of amino acid utilization operons. Unlike most other members of this class, however, the
S. coelicolor bkdR
gene product serves to repress transcription, suggesting that the branched-chain amino acids act as inducers rather than coactivators of transcription. BkdR likely responds to the presence of branched-chain amino acids. Its role in transcriptional regulation may be rationalized by the fact that transition from vegetative growth to aerial mycelium production, the first stage of morphological development in these complex bacteria, is coincident with extensive cellular lysis generating abundant amounts of protein that likely serve as the predominant source of carbon and nitrogen for metabolism. We suggest that
bkdR
plays a key role in the ability of
Streptomyces
species to sense nutrient availability and redirect metabolism for the utilization of branched-chain amino acids for energy, carbon, and perhaps even morphogen synthesis. A null mutant of
bkdR
is itself defective in morphogenesis and antibiotic production, suggesting that the role of the
bkdR
gene product may be more global than specific nutrient utilization.
The Cpx Envelope Stress Response Affects Expression of the Type IV Bundle-Forming Pili of EnteropathogenicEscherichiacoli
Authors: Nevesinjac Anna Z. , Raivio Tracy L. 
Published: January 2005

ABSTRACTThe Cpx envelope stress response mediates adaptation to potentially lethal envelope stresses inEscherichiacoli. The two-component regulatory system consisting of the sensor kinase CpxA and the response regulator CpxR senses and mediates adaptation to envelope insults believed to result in protein misfolding in this compartment. Recently, a role was demonstrated for the Cpx response in the biogenesis of P pili, attachment organelles expressed by uropathogenicE. coli. CpxA senses misfolded P pilus assembly intermediates and initiates increased expression of both assembly and regulatory factors required for P pilus elaboration. In this report, we demonstrate that the Cpx response is also involved in the expression of the type IV bundle-forming pili of enteropathogenicE. coli(EPEC). Bundle-forming pili were not elaborated from an exogenous promoter inE. colilaboratory strain MC4100 unless the Cpx pathway was constitutively activated. Further, an EPECcpxRmutant synthesized diminished levels of bundle-forming pili and was significantly affected in adherence to epithelial cells. Since type IV bundle-forming pili are very different from chaperone-usher-type P pili in both form and biogenesis, our results suggest that the Cpx envelope stress response plays a general role in the expression of envelope-localized organelles with diverse structures and assembly pathways.
Biochemical Activities of the
absA
Two-Component System of
Streptomyces coelicolor
Authors: Sheeler Nancy L. , MacMillan Susan V. , Nodwell Justin R. 
Published: January 2005

ABSTRACT

The AbsA1 sensor kinase and its cognate response regulator AbsA2 are important regulators of antibiotic synthesis in
Streptomyces coelicolor
. While certain point mutations in
absA1
reduce or eliminate the synthesis of several antibiotics, null mutations in these genes bring about enhanced antibiotic synthesis. We show here that AbsA1, which is unusual in sequence and structure, is both an AbsA2 kinase and an AbsA2∼P phosphatase. The half-life of AbsA2∼P in solution is 68.6 min, consistent with a role in maintaining a relatively stable state of transcriptional repression or activation. We find that mutations in the
absA
locus that enhance antibiotic synthesis impair AbsA2 kinase activity and that mutations that repress antibiotic synthesis impair AbsA2∼P phosphatase activity. These results support a model in which the phosphorylation state of AbsA2 is determined by the balance of the kinase and phosphatase activities of AbsA1 and where AbsA2∼P represses antibiotic biosynthetic genes either directly or indirectly.
Structural and Genetic Characterization of Enterohemorrhagic
Escherichia coli
O145 O Antigen and Development of an O145 Serogroup-Specific PCR Assay
Authors: Feng Lu , Senchenkova Sof'ya N. , Tao Jiang , Shashkov Alexander S. , Liu Bin , Shevelev Sergei D. , Reeves Peter R. , Xu Jianguo , Knirel Yuriy A. , Wang Lei 
Published: January 2005

ABSTRACT

Enterohemorrhagic
Escherichia coli
O145 strains are emerging as causes of hemorrhagic colitis and hemolytic uremic syndrome. In this study, we present the structure of the
E. coli
O145 O antigen and the sequence of its gene cluster. The O145 antigen has repeat units containing three monosaccharide residues: 2-acetamido-2-deoxy-
d
-glucose (GlcNAc), 2-acetamidoylamino-2,6-dideoxy-
l
-galactose, and
N
-acetylneuraminic acid. It is very closely related to
Salmonella enterica
serovar Touera and
S. enterica
subsp.
arizonae
O21 antigen. The
E. coli
O145 gene cluster is located between the JUMPStart sequence and the
gnd
gene and consists of 15 open reading frames. Putative genes for the synthesis of the O-antigen constituents, for sugar transferase, and for O-antigen processing were annotated based on sequence similarities and the presence of conserved regions. The putative genes located in the
E. coli
O145 O-antigen gene cluster accounted for all functions expected for synthesis of the structure. An
E. coli
O145 serogroup-specific PCR assay based on the genes
wzx
and
wzy
was also developed by screening
E. coli
and
Shigella
isolates of different serotypes.
SigB-Dependent In Vitro Transcription ofprfAand Some Newly Identified Genes ofListeria monocytogenesWhose Expression Is Affected by PrfA In Vivo
Authors: Rauch Marcus , Luo Qin , Müller-Altrock Stefanie , Goebel Werner 
Published: January 2005

ABSTRACTRecent studies have identified several new genes inListeria monocytogeneswhich are positively or negatively affected by PrfA and grouped into three classes (E. Milohanic et al., Mol. Microbiol.47:1613-1625, 2003). In vitro transcription performed with promoters of some class III genes showed strict SigB-dependent but PrfA-independent transcription initiation. Transcription starting at theprfApromoter PprfA2was also optimal with SigB-loaded RNA polymerase, suggesting a direct link between SigB- and PrfA-dependent gene expression.
The Royal Society of Medicine
Authors: Hunting P 
Published: January 2005

Abstract
With a membership of just over 17 500 the Royal Society of Medicine is the largest medical society in Britain. Its ancestor, the Medical and Chirurgical Society of London, was founded in 1805 when a band of malcontents seceded from the Medical Society of London. By the charter of 1834 the Society became the Royal Medical and Chirurgical Society, which amalgamated with over a dozen other societies to create the Royal Society of Medicine in 1907. It occupies number 1 Wimpole Street, a monumental building that has been redeveloped for the Society’s bicentenary in 2005.
National review of urology outpatient practice in the UK
Authors: Gilmore P E , Shackley D C , Clarke N W , Betts C D , O’Flynn K J 
Published: January 2005

AbstractObjectiveTo audit the current UK outpatient workload and compare this to the national standards as set out by the British Association of Urological Surgeons (BAUS) in A Quality Urological Service for Patients in the New Millennium published in October 2000.Participants520 UK (NHS) and 21 Republic of Ireland (non-NHS) consultant urologists registered with BAUS in 2000.Main outcome measuresExtent to which consultant urologists are able to comply with guidelines set out by their specialist association, the BAUS and by the Royal College of Surgeons of England.ResultsThe questionnaire return rate was 61% (318/520; regional range 42%–75%). The median “routine” clinics/week was two (1–5) with a mean of 13 (1–40) new and 26 (7–80) follow ups. Fifteen percent (49/318) of consultants worked alone in clinic; of the remainder assistance included specialist registrar 67% (212/318), staff grade/associate specialist 32% (102/318), senior house officer 53% (172/318), and pre-registration house officer 2% (7/318). Only 21% (66/318; regional range 0%–46%) of responding consultants followed the BAUS recommendations for outpatient workload/manpower.ConclusionsA minority of consultants are able to adhere to the outpatient workload guidelines as set out by BAUS council in 2000. In addition, there appears to be significant variations within and between training regions. Development of this project into a regional audit tool may allow intraregional guideline formation governing hospital outpatient workload.
Towards optimization of selective photothermolysis: prothrombotic pharmaceutical agents as potential adjuvants in laser treatment of port wine stains
Authors: Beek Johan F. , Moldovan Nicanor I. , van der Horst Chantal M. A. M. , van Gemert Martin J. C. , Heger Michal 
Published: January 2005

SummaryFor the past two decades much research on selective photothermolysis of port wine stain vasculature has been devoted to optimizing laser parameters. Unfortunately, 60% of patients still respond suboptimally to laser therapy, despite significant innovations in treatment strategies and laser technology. Here we present a novel treatment approach based on combining selective photothermolysis with the administration of prothrombotic and/or anti-fibrinolytic pharmaceutical agents, with the aim of enhancing vaso-occlusion and post-treatment remodelling in difficult-to-target vessels. A hypercoagulable state of blood will instill laser-induced occlusive thrombosis in a wider array of vessel diameters at greater dermal depths, whereby larger vascular segments will ultimately undergo the chronic inflammatory processes that result in blood volume reduction, and thus lesional blanching. With thrombosis as a primary trigger for these inflammatory processes, we have extrapolated the thresh-old damage profile that is required for clinically relevant thrombus formation. Consequently, a recently proposed model of thrombus organization, in which recanalization is associated with endothelial progenitor cell-mediated neovasculogenesis, is elaborated in the framework of lesional blanching and juxtaposed to angiogenic reconstruction of affected dermal vasculature. Since neovasculogenesis and angiogenesis are regulated by the degree of vaso-occlusion and corollary drop in local oxygen tension, both can be manipulated by the administration of procoagulant pharmaceuticals. Lastly, in an effort to optimally balance selective photothermolysis with pharmacokinetics and clinical safety, the use of a gold nanoshell drug delivery system, in which the procoagulant drugs are encapsulated by a wavelength-modulated, gold-coated polymer matrix, is proposed. We have termed this modality site-specific pharmaco-laser therapy.
The spacer domain of ADAMTS13 contains a major binding site for antibodies in patients with thrombotic thrombocytopenic purpura
Authors: Luken Brenda M. , Turenhout Ellen A.M. , Hulstein Janine J.J. , Van Mourik Jan A. , Fijnheer Rob , Voorberg Jan 
Published: January 2005

SummaryThrombotic thrombocytopenic purpura (TTP) is a microangiopathy often associated with a severely decreased activity of ADAMTS13. In plasma of the majority of patients withTTP, antibodies are present that inhibit the vonWillebrand factor (VWF) processing activity of ADAMTS13.We describe a sensitive assay that monitors binding of recombinant ADAMTS13 to immobilized IgG derived from patient plasma. Analysis of fifteen patients with TTP and severely reduced ADAMTS13 activity revealed that in all patients antibodies directed toADAMTS13 were present. Levels of anti-ADAMTS13 antibodies varied considerably among patients, specific antibody levels in plasma range from less than 100 ng/ml to over 1 μg/ml. Longitudinal analysis in three patients revealed that anti-ADAMTS13 antibody levels declined with different kinetics. For further characterization of anti- ADAMTS13 antibodies, we prepared a series of recombinan fragments corresponding to the various ADAMTS13 domains. All seven TTP plasma samples tested, showed reactivity of antibodies towards a fragment consisting of the disintegrin/ TSR1/cysteine-rich/spacer domains. In one patient, we also observed reactivity towards the TSR2–8 repeats. No binding of antibodies to propeptide, metalloprotease and CUB domains was detected. To further delineate the binding site in the disintegrin/ TSR1/cysteine-rich/spacer region, we prepared additional ADAMTS13 fragments. Antibodies directed towards the cysteine- rich/spacer fragment were found in all plasma samples analyzed. No antibodies reacting with the disintegrin/TSR1 domains were detected. A recombinant fragment comprising the spacer domain was recognized by all patients samples analyzed, suggesting that the 130-amino-acid spacer domain harbors a major binding site for anti-ADAMTS-13 antibodies.
Identification and characterization of the plasma kallikrein-kinin system inhibitor, haemaphysalin, from hard tick, Haemaphysalis longicornis
Authors: Kato Noriko , Okayama Takahide , Isawa Haruhiko , Yuda Masao , Chinzei Yasuo , Iwanaga Shiroh 
Published: January 2005

SummaryThe plasma kallikrein-kinin system inhibitor, haemaphysalin, from the hard tick, Haemaphysalis longicornis, was identified. It was found that haemaphysalin inhibited activation of the plasma kallikrein-kinin system by interfering with reciprocal activation between factor XII and prekallikrein. It did not, however, inhibit amidolytic activities of factor XIIa and kallikrein. Direct binding assay indicated that factor XII/XIIa and high molecular weight kininogen (HK) are the target molecules of haemaphysalin, and that Zn2+ ions are involved in the interactions of haemaphysalin with these target molecules. This suggests that haemaphysalin interacts with target molecules by recognizing their conformational changes induced by Zn2+ ions. Furthermore, haemaphysalin interacted with the fibronectin type II domain and domain D5, the cell binding domains of factor XII and HK, respectively. This finding suggests that haemaphysalin interferes with the association of factor XII and the prekallikrein-HK complex with a biologic activating surface by binding to these cell-binding domains, leading to inhibition of the reciprocal activation between factor XII and prekallikrein.
Ultrasound elastography for the age determination of venous thrombi
Authors: Barbera Letterio , Muth-Werthmann Dajana , Siebers Stefan , Ermert Helmut , Philippou Stathis , Mumme Achim , Geier Bruno 
Published: January 2005

SummaryThe exact age determination of venous thrombi is important if thrombolytic therapy or surgical thrombectomy is considered. Clinical symptoms as well as duplex-ultrasound and phlebography are unreliable in this respect and do not allow an exact age estimation. Ultrasound elastography can provide information about the elastic properties of thrombi. Since thrombus elasticity decreases with age due to the organisation process, it should be possible to use elastography to stage the degree of organisation and thereby determine the age of venous thrombi. Experimental venous thrombi aging 1, 3, 6, 9, 12 and 15 days were created in a porcine model by laparoscopic ligation of the infrarenal Vena cava in combination with transfemoral infusion of thrombin. The thrombosed iliac veins were explanted and embedded in gelatine, after that they underwent examination by ultrasound elastography. In addition, histological evaluation of the thrombi was performed. Elastography demonstrated a decline in thrombus elasticity between days 6 and 12 with the 12-day-old thrombi being about 3 times harder then the 6-dayold thrombi. This correlated with the histological findings, which demonstrated a marked increase in fibroblast and collagen production in the clots during this time, with the 12– and 15-day thrombi showing signs of advanced organisation. In conclusion, in an experimental setting, ultrasound elastography was helpful in determining the exact age of venous thrombi. The differences in elasticity were most pronounced between days 6 and 12, which is also the most relevant time frame when considering invasive therapies in human venous thrombosis.
Roles of the multifunctional glycoprotein, emmprin (basigin; CD147), in tumour progression
Authors: Yan Li , Zucker Stanley , Toole Bryan P. 
Published: January 2005

SummaryEmmprin (basigin;CD147) is a widely distributed cell surface glycoprotein that belongs to the Ig superfamily and is highly enriched on the surface of malignant tumour cells. Emmprin is involved in numerous physiological and pathological systems and exhibits several molecular and cellular characteristics, but a major function of emmprin is stimulation of synthesis of several matrix metalloproteinases. In tumours, emmprin most likely stimulates matrix metalloproteinase production in stromal fibroblasts and endothelial cells as well as in tumour cells themselves by a mechanism involving homophilic interactions between emmprin molecules on apposing cells or on neighbouring cells after membrane vesicle shedding. Membrane-associated cofactors, including caveolin-1 and annexin II, regulate emmprin activity. Emmprin induces angiogenesis via stimulation of VEGF production, invasiveness via stimulation of matrix metalloproteinase production and multidrug resistance via hyaluronan-mediated up-regulation of ErbB2 signaling and cell survival pathway activities. Although the detailed mechanisms whereby it regulates these numerous phenomena are not yet known, it is clear that emmprin is a major mediator of malignant cell behavior.
The urokinase plasminogen activator and its receptor
Authors: Alfano Daniela , Franco Paola , Vocca Immacolata , Gambi Nadia , Pisa Viviana , Mancini Alessandro , Caputi Mario , Carriero Maria Vincenza , Iaccarino Ingram , Stoppelli Maria Patrizia 
Published: January 2005

SummaryThe urinary-type plasminogen activator, or uPA, controls matrix degradation through the conversion of plasminogen into plasmin and is regarded as the critical trigger for plasmin generation during cell migration and invasion, under physiological and pathological conditions (such as cancer metastasis).The proteolytic activity of uPA is responsible for the activation or release of several growth factors and modulates the cell survival/apoptosis ratio through the dynamic control of cell-matrix contacts. The urokinase receptor (uPAR), binding to the EGF-like domain of uPA, directs membrane-associated extracellular proteolysis and signals through transmembrane proteins, thus regulating cell migration, adhesion and cytoskeletal status. However, recent evidence highlights an intricate relationship linking the uPA/uPAR system to cell growth and apoptosis.
Poly(ADP-ribosyl)ation, a molecular switch of transcription, shows an attractive relationship with urokinase expression
Authors: Caldini Riccardo , Rosso Mario Del , Chevanne Marta 
Published: January 2005

SummaryPoly(ADP-ribosyl)ation is a posttranslational modification of proteins that consists in the transfer of ADP-ribose units from NAD+ onto protein acceptors to form long and branched polymers. PARP activity is stimulated either by genotoxic stimuli or by environmental factors. The negative charged polymers alter functional activity of several proteins involved in genome stability, gene expression, cell proliferation and differentiation. Increasing evidence supports the view that PARP, for its crucial position in DNA repair and DNA transcription, influences cell survival not only during tissue injure, but also in environmental homeostasis modification. Therefore, it may be considered a molecular switch in the control of transcription, eventually leading to the choice of cell for life and death. This review summarizes the recent findings on PARP activity and special emphasis is given to its role in urokinase-type plasminogen activator upregulation.
CD4+CD25+ regulatory T cells control induction of autoimmune hemolytic anemia
Authors: Mqadmi Amina , Zheng Xiaoying , Yazdanbakhsh Karina 
Published: January 2005

Abstract
Autoimmune hemolytic anemia (AIHA) is the result of increased destruction of red blood cells (RBCs) due to the production of autoantibodies, and it can be life-threatening. To study the mechanisms that trigger AIHA, we used the Marshall-Clarke and Playfair model of murine AIHA, in which mice repeatedly immunized with rat RBCs develop erythrocyte autoantibodies as well as rat-specific alloantibodies. We analyzed the role of CD25+ T-regulatory subsets in controlling AIHA in C57/Bl6 mice using antibody depletion studies. Treatment with anti-CD25 antibody but not isotype control prior to immunization with rat RBCs increased the incidence of AIHA from 30% to 90%. Adoptive transfer of purified splenic population of CD4+CD25+ but not CD4+CD25- cells from immunized mice into naive recipients prevented the induction of autoantibody production. Altogether, our data establish a critical role for CD4+CD25+ cells for control of AIHA, which may help to establish therapeutic strategies for treatment of AIHA.
Changes in extracranial arteries in obstructive sleep apnoea
Authors: Schulz R. , Seeger W. , Fegbeutel C. , Hüsken H. , Bödeker R. H. , Tillmanns H. , Grebe M. 
Published: January 2005

Obstructive sleep apnoea (OSA) is linked with increased cardiovascular morbidity and mortality, possibly through an enhancement of atherosclerotic vascular changes. Up to now, however, only a few studies have tried to evaluate the occurrence of atherosclerosis in patients with OSA.In the present study, ultrasonography of the large extracranial vessels was performed in a group of consecutively admitted OSA patients (n = 35) and a control group of non-OSA patients (n = 35). Common carotid artery-intima media thickness (CCA-IMT) was measured at the far wall of both proximal carotid arteries. Furthermore, the presence of plaques and stenoses of the extracranial vessels was determined. All measurements were carried out blinded to the status of the patients.In the OSA group, CCA-IMT was significantly increased when compared with the non-OSA patients and was related to the degree of nocturnal hypoxia. Additionally, the formation of plaques was more pronounced and extracranial vessel stenosis was more common in the OSA patients.In conclusion, these findings are in favour of an independent influence of obstructive sleep apnoea on atherosclerotic changes of the arterial wall, and represent further strong arguments for obstructive sleep apnoea being a risk factor on its own for the emergence of cardiovascular disease.