bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of hypoglycaemia awareness using continuous glucose monitoring
Authors: Kubiak T. , Hermanns N. , Schreckling H. J. , Kulzer B. , Haak T. 
Published: April 2004

AbstractAims  To investigate the possibility of assessing hypoglycaemia awareness in patients with Type 1 diabetes using continuous glucose monitoring.Methods  Twenty patients with Type 1 diabetes were investigated. Ten patients with Type 1 diabetes and strongly impaired hypoglycaemia awareness were compared with 10 patients with intact hypoglycaemia awareness regarding quality of hypoglycaemia perception (number of undetected hypoglycaemic episodes per 24 h, glucose level < 3.3 mmol/l). Hypoglycaemia detection was assessed using the event function of the Continuous Glucose Monitoring System (CGMS™; Medtronic MiniMed®, Northridge, CA, USA). Patients were instructed to enter an event upon suspecting being hypoglycaemic.Results  Satisfactory CGMS performance could be achieved [mean r = 0.893 between calibration measurements and CGMS data, mean absolute difference (MAD) = 20.6%], although artefacts were observable and had to be controlled. Hypoglycaemia unaware patients showed a significantly higher total number of hypoglycaemic episodes (P < 0.05), number of undetected hypoglycaemic episodes (P < 0.01), and mean glucose levels (P < 0.05). Even in aware patients, undetected hypoglycaemia was observable. No significant differences regarding occurrence of nocturnal hypoglycaemia were observable.Conclusions  The possibility of direct assessment of hypoglycaemia awareness using continuous glucose monitoring was demonstrated. Its application in clinical practice could be of use for assessing hypoglycaemia perception and evaluating the impact of treatment changes on hypoglycaemia awareness.
Structural and Genetic Characterization of Glycosylation of Type a Flagellin in
Pseudomonas aeruginosa
Authors: Schirm M. , Arora S. K. , Verma A. , Vinogradov E. , Thibault P. , Ramphal R. , Logan S. M. 
Published: April 2004

ABSTRACT

Type a flagellins from two strains of
Pseudomonas aeruginosa
, strains PAK and JJ692, were found to be glycosylated with unique glycan structures. In both cases, two sites of O-linked glycosylation were identified on each monomer, and these sites were localized to the central, surface-exposed domain of the monomer in the assembled filament. The PAK flagellin was modified with a heterogeneous glycan comprising up to 11 monosaccharide units that were O linked through a rhamnose residue to the protein backbone. The flagellin of JJ692 was less complex and had a single rhamnose substitution at each site. The role of the glycosylation island gene cluster in the production of each of these glycosyl moieties was investigated. These studies revealed that the
orfA
and
orfN
genes were required for attachment of the heterologous glycan and the proximal rhamnose residue, respectively.
Identification of PimR as a Positive Regulator of Pimaricin Biosynthesis in
Streptomyces natalensis
Authors: Antón Nuria , Mendes Marta V. , Martín Juan F. , Aparicio Jesús F. 
Published: April 2004

ABSTRACT

Sequencing of the DNA region on the left fringe of the pimaricin gene cluster revealed the presence of a 3.6-kb gene,
pimR
, whose deduced product (1,198 amino acid residues) was found to have amino acid sequence homology with bacterial regulatory proteins. Database comparisons revealed that PimR represents the archetype of a new class of regulators, combining a
Streptomyces
antibiotic regulatory protein (SARP)-like N-terminal section with a C-terminal half homologous to guanylate cyclases and large ATP-binding regulators of the LuxR family. Gene replacement of
pimR
from
Streptomyces natalensis
chromosome results in a complete loss of pimaricin production, suggesting that PimR is a positive regulator of pimaricin biosynthesis. Gene expression analysis by reverse transcriptase PCR (RT-PCR) of the pimaricin gene cluster revealed that
S. natalensis
ΔPimR shows no expression at all of the cholesterol oxidase-encoding gene
pimE
, and very low level transcription of the remaining genes of the cluster except for the mutant
pimR
gene, thus demonstrating that this regulator activates the transcription of all the genes belonging to the pimaricin gene cluster but not its own transcription.
ScaC, an Adaptor Protein Carrying a Novel Cohesin That Expands the Dockerin-Binding Repertoire of the
Ruminococcus flavefaciens
17 Cellulosome
Authors: Rincón Marco T. , Martin Jennifer C. , Aurilia Vincenzo , McCrae Sheila I. , Rucklidge Garry J. , Reid Martin D. , Bayer Edward A. , Lamed Raphael , Flint Harry J. 
Published: April 2004

ABSTRACT

A new gene, designated
scaC
and encoding a protein carrying a single cohesin, was identified in the cellulolytic rumen anaerobe
Ruminococcus flavefaciens
17 as part of a gene cluster that also codes for the cellulosome structural components ScaA and ScaB. Phylogenetic analysis showed that the sequence of the ScaC cohesin is distinct from the sequences of other cohesins, including the sequences of
R. flavefaciens
ScaA and ScaB. The
scaC
gene product also includes at its C terminus a dockerin module that closely resembles those found in
R. flavefaciens
enzymes that bind to the cohesins of the primary ScaA scaffoldin. The putative cohesin domain and the C-terminal dockerin module were cloned and overexpressed in
Escherichia coli
as His
6
-tagged products (ScaC-Coh and ScaC-Doc, respectively). Affinity probing of protein extracts of
R. flavefaciens
17 separated in one-dimensional and two-dimensional gels with recombinant cohesins from ScaC and ScaA revealed that two distinct subsets of native proteins interact with ScaC-Coh and ScaA-Coh. Furthermore, ScaC-Coh failed to interact with the recombinant dockerin module from the enzyme EndB that is recognized by ScaA cohesins. On the other hand, ScaC-Doc was shown to interact specifically with the recombinant cohesin domain from ScaA, and the ScaA-Coh probe was shown to interact with a native 29-kDa protein spot identified as ScaC by matrix-assisted laser desorption ionization—time of flight mass spectrometry. These results suggest that ScaC plays the role of an adaptor scaffoldin that is bound to ScaA via the ScaC dockerin module, which, via the distinctive ScaC cohesin, expands the range of proteins that can bind to the ScaA-based enzyme complex.
Evidence for the Active Role of a Novel Nuclease from
Helicobacter pylori
in the Horizontal Transfer of Genetic Information
Authors: O'Rourke Eyleen J. , Pinto A. Viviana , Petroni E. Alejandro , Tolmasky Marcelo E. , Ielpi Luis 
Published: April 2004

ABSTRACT

Helicobacter pylori
is a gram-negative bacterium that colonizes the human stomach, causes gastritis, and is associated with ulcers and gastric cancer.
H. pylori
is naturally competent for transformation. Natural genetic transformation is believed to be essential for the genetic plasticity observed in this species. While the relevance of horizontal gene transfer in
H. pylori
adaptiveness and antibiotic resistance is well documented, the DNA transformation machinery components are barely known. No enzymatic activity associated with the transformation process has been determined experimentally and described. We isolated, microsequenced, and cloned a major DNA nuclease from
H. pylori.
This protein, encoded by the open reading frame
hp0323
, was expressed in
Escherichia coli
. The purified protein, NucT, has a cation-independent thermostable nuclease activity that preferentially cleaves single-stranded DNA. NucT is associated with the membrane. NucT-deficient
H. pylori
strains are one or more orders of magnitude less efficient than the parental strain for transformation with either chromosomal or self-replicating plasmid DNA. To the best of our knowledge, NucT is the first nuclease identified in a gram-negative natural transformation system, and its existence suggests that there is a mechanism of DNA processing and uptake similar to the mechanisms in well-studied gram-positive systems.
Modular Organization of the Phd Repressor/Antitoxin Protein
Authors: Smith Jeremy Allen , Magnuson Roy David 
Published: April 2004

ABSTRACT

The P1 plasmid addiction operon is a compact genetic structure consisting of promoter, operator, antitoxin gene (
phd
), and toxin gene (
doc
). The 73-amino-acid antitoxin protein, Phd, has two distinct functions: it represses transcription (by binding to its operator) and it prevents host death (by binding and neutralizing the toxin). Here, we show that the N terminus of Phd is required for repressor but not antitoxin activity. Conversely, the C terminus is required for antitoxin but not repressor activity. Only a quarter of the protein, the resolution limit of this analysis, was required for both activities. We suggest that the plasmid addiction operon is a composite of two evolutionarily separable modules, an operator-repressor module and an antitoxin-toxin module. Consideration of similar antitoxin proteins and their surroundings indicates that modular exchange may contribute to antitoxin and operon diversity.
Molecular Characterization ofBorrelia burgdorferi erpPromoter/Operator Elements
Authors: Babb Kelly , McAlister Jason D. , Miller Jennifer C. , Stevenson Brian 
Published: April 2004

ABSTRACTManyBorrelia burgdorferiErp outer surface proteins have been demonstrated to bind the host complement regulator factor H, which likely contributes to the ability of these organisms to evade the host innate immune system.B. burgdorfericontrols Erp protein synthesis throughout the bacterial infectious cycle, producing the proteins during mammalian infections but repressing their synthesis during tick infections. Defining the mechanism by whichB. burgdorferiregulates the expression of these virulence determinants will provide important insight into the biological and pathogenic properties of the Lyme disease spirochete. The present study demonstrates that two highly conserved DNA sequences located 5′ oferpoperons specifically bind bacterial proteins. Analyses withB. burgdorferiof transcriptional fusions betweenerppromoter/operator DNAs and the gene for green fluorescent protein indicated that the expression of these operons is regulated at the level of transcriptional initiation. These analyses also indicated significant differences in the promoter strengths of variouserpoperons, which likely accounts for reported variations in expression levels of different Erp proteins. Mutagenesis of promoter-gfpfusions demonstrated that at least one of the proteins which binderpoperator DNA functions as a repressor of transcription.
Mutational Analysis of RsbT, an Activator of theBacillus subtilisStress Response Transcription Factor, σB
Authors: Woodbury Robyn L. , Luo Tingqiu , Grant Lindsay , Haldenwang W. G. 
Published: April 2004

ABSTRACTσB, the stress-activated σ factor ofBacillus subtilis, requires the RsbT protein as an essential positive regulator of its physical stress pathway. Stress triggers RsbT to both inactivate the principal negative regulator of the physical stress pathway (RsbS) by phosphorylation and activate a phosphatase (RsbU) required for σBinduction. Neither the regions of RsbT that are involved in responding to stress signaling nor those required for downstream events have been established. We used alanine scanning mutagenesis to examine the contributions of RsbT's charged amino acids to the protein's stability and activities. Eleven of eighteenrsbTmutations blocked σBinduction by stress. The carboxy terminus of RsbT proved to be particularly important for accumulation inBacillus subtilis. Four of the five most carboxy-terminal mutations yieldedrsbTalleles whose products were undetectable inB. subtilisextracts. Charged amino acids in the central region of RsbT were less critical, with four of the five substitutions in this region having no measurable effect on RsbT accumulation or activity. Only when the substitutions extended into a region of kinase homology was σBinduction affected. Six other RsbT variants, although present at levels adequate for activity, failed to activate σBand displayed significant changes in their ability to interact with RsbT's normal binding partners in a yeast dihybrid assay. These changes either dramatically altered the proteins' tertiary structure without affecting their stability or defined regions of RsbT that are involved in multiple interactions.
Conserved Glycines in the C Terminus of MinC Proteins Are Implicated in Their Functionality as Cell Division Inhibitors
Authors: Ramirez-Arcos S. , Greco V. , Douglas H. , Tessier D. , Fan D. , Szeto J. , Wang J. , Dillon J. R. 
Published: April 2004

ABSTRACT

Alignment of 36 MinC sequences revealed four completely conserved C-terminal glycines. As MinC inhibits cytokinesis in
Neisseria gonorrhoeae
and
Escherichia coli
, the functional importance of these glycines in
N. gonorrhoeae
MinC (MinC
Ng
) and
E. coli
MinC (MinC
Ec
) was investigated through amino acid substitution by using site-directed mutagenesis. Each mutant was evaluated for its ability to arrest cell division and to interact with itself and MinD. In contrast to overexpression of wild-type MinC, overexpression of mutant proteins in
E. coli
did not induce filamentation, indicating that they lost functionality. Yeast two-hybrid studies showed that MinC
Ec
interacts with itself and MinD
Ec
; however, no interactions involving MinC
Ng
were detected. Therefore, a recombinant MinC protein, with the N terminus of MinC
Ec
and the C terminus of MinC
Ng
, was designed to test for a MinC
Ng
-MinD
Ng
interaction. Each MinC mutant interacted with either MinC or MinD but not both, indicating the specificity of glycine residues for particular protein-protein interactions. Each glycine was mapped on the C-terminal surfaces (A, B, and C) of the solved
Thermotoga maritima
MinC structure. We found that MinC
Ec
G161, residing in close proximity to the A surface, is involved in homodimerization, which is essential for MinC function. Glycines corresponding to MinC
Ec
G135, G154, and G171, located within or adjacent to the B-C surface junction, are critical for MinC-MinD interactions. Circular dichroism revealed no gross structural perturbations of the mutant proteins, although the contribution of glycines to protein flexibility and stability cannot be discounted. Using molecular modeling, we propose that exposed conserved MinC glycines interact with exposed residues of the α-7 helix of MinD.
A Promoter Mutation Causes Differential Nitrate Reductase Activity of
Mycobacterium tuberculosis
and
Mycobacterium bovis
Authors: Stermann Marion , Sedlacek Ludwig , Maass Silvia , Bange Franz-Christoph 
Published: April 2004

ABSTRACT

The recent publication of the genome sequence of
Mycobacterium bovis
showed >99.95% identity to
M. tuberculosis
. No genes unique to
M. bovis
were found. Instead numerous single-nucleotide polymorphisms (SNPs) were identified. This has led to the hypothesis that differential gene expression due to SNPs might explain the differences between the human and bovine tubercle bacilli. One phenotypic distinction between
M. tuberculosis
and
M. bovis
is nitrate reduction, which not only is an essential diagnostic tool but also contributes to mycobacterial pathogenesis. We previously showed that
narGHJI
encodes a nitrate reductase in both
M. tuberculosis
and
M. bovis
and that NarGHJI-mediated nitrate reductase activity was substantially higher in the human tubercle bacillus. In the present study we used a genetic approach to demonstrate that an SNP within the promoter of the nitrate reductase gene cluster
narGHJI
is responsible for the different nitrate reductase activity of
M. tuberculosis
and
M. bovis
. This is the first example of an SNP that leads to differential gene expression between the human and bovine tubercle bacilli.
Cold blast furnace syndrome: a new source of toxic inhalation by nitrogen oxides: Table 1
Authors: Tague I , Llewellin P , Burton K , Buchan R , Yates D H 
Published: April 2004

Aim:To describe a new toxic inhalation syndrome in blast furnace workers.Methods:Fourteen workers developed acute respiratory symptoms shortly after exposure to “air blast” from blast furnace tuyeres. These included chest tightness, dyspnoea, rigors, and diaphoresis. Chest radiographs showed pulmonary infiltrates, and lung function a restrictive abnormality. This report includes a description of clinical features of the affected workers and elucidation of the probable cause of the outbreak.Results:Clinical features and occupational hygiene measurements suggested the most likely cause was inhalation of nitrogen oxides at high pressure and temperature. While the task could not be eliminated, engineering controls were implemented to control the hazard. No further cases have occurred.Conclusions:“Cold blast furnace syndrome” represents a previously undescribed hazard of blast furnace work, probably due to inhalation of nitrogen oxides. It should be considered in the differential diagnosis of acute toxic inhalational injuries in blast furnace workers.
Exposure of pregnant women to tap water related activities
Authors: Kaur S , Nieuwenhuijsen M J , Ferrier H , Steer P 
Published: April 2004

Background:Evidence for an association between exposure of pregnant women to chlorination disinfection by-products and adverse birth outcomes is inconsistent and inconclusive.Aims:To evaluate the use of a questionnaire in a population of pregnant women to assess their exposure to water, examine the validity of the questionnaire by a seven day diary, and to obtain a better understanding of the exposure of pregnant women to water in Central London.Methods:A total of 147 pregnant women were asked to complete a questionnaire. Information was requested on their exposure to water from cooking and washing up, showering and bathing, food and drink, and swimming. Demographic and socioeconomic information were also recorded. For validation purposes, women were asked to complete a seven day diary at home.Results:The average exposure duration was 338.5 min/week for cooking and washing up, 172.2 min/week for bathing and showering, and 67.9 min/month for swimming. The total fluid intake was 18.9 l/week of which, on average, 18% was cold tap water; 30% of this tap water was consumed outside the home. The correlation between questionnaire and diary data was generally good to very good, although women tended to overestimate their exposure in the questionnaire compared to the diary.Conclusions:Information was obtained on the daily exposure of pregnant women in Central London to chlorinated water at home, work, and elsewhere. The questionnaire was found to be a valid method to assess the exposure of pregnant women to water and the response rate was higher than for diaries.
All-cause and cause specific mortality in a cohort of 20 000 construction workers; results from a 10 year follow up
Authors: Arndt V , Rothenbacher D , Daniel U , Zschenderlein B , Schuberth S , Brenner H 
Published: April 2004

Background:Construction workers are potentially exposed to many health hazards, including human carcinogens such as asbestos, silica, and other so-called “bystander” exposures from shared work places. The construction industry is also a high risk trade with respect to accidents.Methods:A total of 19 943 male employees from the German construction industry who underwent occupational health examinations between 1986 and 1992 were followed up until 1999/2000.Results:A total of 818 deaths occurred during the 10 year follow up (SMR 0.71; 95% CI 0.66 to 0.76). Among those were 299 deaths due to cancer (SMR 0.89; 95% CI 0.79 to 1.00) and 312 deaths due to cardiovascular diseases (SMR 0.59; 95% CI 0.51 to 0.68). Increased risk of mortality was found for non-transport accidents (SMR 1.61; 95% CI 1.15 to 2.27), especially due to falls (SMR 1.87; 95% CI 1.18 to 2.92) and being struck by falling objects (SMR 1.90; 95% CI 0.88 to 3.64). Excess mortality due to non-transport accidents was highest among labourers and young and middle-aged workers. Risk of getting killed by falling objects was especially high for foreign workers (SMR 4.28; 95% CI 1.17 to 11.01) and labourers (SMR 6.01; 95% CI 1.63 to 15.29).Conclusion:Fatal injuries due to falls and being struck by falling objects pose particular health hazards among construction workers. Further efforts are necessary to reduce the number of fatal accidents and should address young and middle-aged, semi-skilled and foreign workers, in particular. The lower than expected cancer mortality deserves careful interpretation and futher follow up of the cohort.
Molecular Genetics of Type 2 Diabetes—Candidate Genes
Authors: Groop Leif , Ridderstråle Martin 
Published: April 2004

AbstractAbout 150 million people are diagnosed with type 2 diabetes today and it is predicted that this number will double within the next 15 years. There is evidence that type 2 diabetes is inherited; however, it is unlikely that the cause of the explosion of type 2 diabetes is found in our genes. It is rather the rapid change of the environment with an affluent westernized society that triggers the epidemic in genetically predisposed individuals. In this chapter we discuss potential candidate genes that could contribute to this genetic predisposition to type 2 diabetes.
Monogenic Disorders of the β‐Cell
Authors: Pearson Ewan R. , Hattersley Andrew T. 
Published: April 2004

AbstractDefects in pancreatic β‐cell glucose–insulin secretion coupling can cause undersecretion of insulin and hence hyperglycemia and diabetes, or more rarely oversecretion of insulin and hypoglycemia. The most common cause of β‐cell dysfunction is seen in type 2 diabetes but this is polygenic and still imprecisely defined. Monogenic disorders of the β‐cell account for 3–4% of diabetes and so they are an important cause of diabetes in their own right. The recognition of a monogenic etiology of diabetes has clinical management implications determining clinical course, nonpancreatic manifestations, and choice of treatment. In addition to this clinical importance, the discovery and study of monogenic disorders has given further insight into the physiology and pathophysiology of the β‐cell. This chapter will focus on the most prevalent of the monogenic disorders of the β‐cell: maturity‐onset diabetes of the young and mitochondrial inherited diabetes and deafness. We will also discuss hyperinsulinemia, Wolfram syndrome, thiamine responsive megaloblastic anemia syndrome, Wolcott–Rallison syndrome, mutant insulins, and familial hyperproinsulinemia.
Dietary Management of Diabetes Mellitus in India and South East Asia
Authors: Ramachandran Ambady , Snehalatha Chamukuttan , Viswanathan Vijay 
Published: April 2004

AbstractDietary modifications play a major role in the management of diabetes mellitus. It is generally accepted that a high‐carbohydrate, high‐fiber, low‐fat diet with calorie restrictions is the ideal diet. Among the South East Asian populations, as the composition of the prescribed diet is very similar to the usual diet, its acceptance and adherence by the diabetic subjects is fairly easy. Dietary prescription should aim to optimize both glycemia and plasma lipids to help prevent the long‐term vascular and other diabetic complications. Meal planning with food items of low glycemic index with inclusion of plenty of fresh vegetables is advisable. Avoidance of obesity from childhood should be a long‐term goal. Constant motivation through nutrition counseling and education in an appropriate way will help in achieving dietary targets. The younger generation should be given education regarding a healthy diet which will help reduce the occurrence of nutritional deficiencies and obesity, and delay or prevent the onset of diabetes.