bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual Role of TOC1 in the Control of Circadian and Photomorphogenic Responses in Arabidopsis[W]
Authors: Más Paloma , Alabadí David , Yanovsky Marcelo J. , Oyama Tokitaka , Kay Steve A. 
Published: January 2003

AbstractTo examine the role of the TOC1 (TIMING OF CAB EXPRESSION1) gene in the Arabidopsis circadian system, we generated a series of transgenic plants expressing a gradation in TOC1 levels. Silencing of the TOC1 gene causes arrhythmia in constant darkness and in various intensities of red light, whereas in blue light, the clock runs faster in silenced plants than in wild-type plants. Increments in TOC1 gene dosage delayed the pace of the clock, whereas TOC1 overexpression abolished rhythmicity in all light conditions tested. Our results show that TOC1 RNA interference and toc1-2 mutant plants displayed an important reduction in sensitivity to red and far-red light in the control of hypocotyl elongation, whereas increments in TOC1 gene dosage clearly enhanced light sensitivity. Furthermore, the red light–mediated induction of CCA1/LHY expression was decreased in TOC1 RNA interference and toc1-2 mutant plants, indicating a role for TOC1 in the phytochrome regulation of circadian gene expression. We conclude that TOC1 is an important component of the circadian clock in Arabidopsis with a crucial function in the integration of light signals to control circadian and morphogenic responses.
ETHYLENE RESPONSE FACTOR1 Integrates Signals from Ethylene and Jasmonate Pathways in Plant Defense[W]
Authors: Lorenzo Oscar , Piqueras Raquel , Sánchez-Serrano Jose J. , Solano Roberto 
Published: January 2003

Abstract
Cross-talk between ethylene and jasmonate signaling pathways determines the activation of a set of defense responses against pathogens and herbivores. However, the molecular mechanisms that underlie this cross-talk are poorly understood. Here, we show that ethylene and jasmonate pathways converge in the transcriptional activation of ETHYLENE RESPONSE FACTOR1 (ERF1), which encodes a transcription factor that regulates the expression of pathogen response genes that prevent disease progression. The expression of ERF1 can be activated rapidly by ethylene or jasmonate and can be activated synergistically by both hormones. In addition, both signaling pathways are required simultaneously to activate ERF1, because mutations that block any of them prevent ERF1 induction by any of these hormones either alone or in combination. Furthermore, 35S:ERF1 expression can rescue the defense response defects of coi1 (coronative insensitive1) and ein2 (ethylene insensitive2); therefore, it is a likely downstream component of both ethylene and jasmonate signaling pathways. Transcriptome analysis in Col;35S:ERF1 transgenic plants and ethylene/jasmonate-treated wild-type plants further supports the notion that ERF1 regulates in vivo the expression of a large number of genes responsive to both ethylene and jasmonate. These results suggest that ERF1 acts downstream of the intersection between ethylene and jasmonate pathways and suggest that this transcription factor is a key element in the integration of both signals for the regulation of defense response genes.
Microbial Biodiversity: Approaches to Experimental Design and Hypothesis Testing in Primary Scientific Literature from 1975 to 1999
Authors: Morris Cindy E. , Bardin Marc , Berge Odile , Frey-Klett Pascale , Fromin Nathalie , Girardin Hélène , Guinebretière Marie-Hélène , Lebaron Philippe , Thiéry Jean M. , Troussellier Marc 
Published: January 2003

SUMMARYResearch interest in microbial biodiversity over the past 25 years has increased markedly as microbiologists have become interested in the significance of biodiversity for ecological processes and as the industrial, medical, and agricultural applications of this diversity have evolved. One major challenge for studies of microbial habitats is how to account for the diversity of extremely large and heterogeneous populations with samples that represent only a very small fraction of these populations. This review presents an analysis of the way in which the field of microbial biodiversity has exploited sampling, experimental design, and the process of hypothesis testing to meet this challenge. This review is based on a systematic analysis of 753 publications randomly sampled from the primary scientific literature from 1975 to 1999 concerning the microbial biodiversity of eight habitats related to water, soil, plants, and food. These publications illustrate a dominant and growing interest in questions concerning the effect of specific environmental factors on microbial biodiversity, the spatial and temporal heterogeneity of this biodiversity, and quantitative measures of population structure for most of the habitats covered here. Nevertheless, our analysis reveals that descriptions of sampling strategies or other information concerning the representativeness of the sample are often missing from publications, that there is very limited use of statistical tests of hypotheses, and that only a very few publications report the results of multiple independent tests of hypotheses. Examples are cited of different approaches and constraints to experimental design and hypothesis testing in studies of microbial biodiversity. To prompt a more rigorous approach to unambiguous evaluation of the impact of microbial biodiversity on ecological processes, we present guidelines for reporting information about experimental design, sampling strategies, and analyses of results in publications concerning microbial biodiversity.
Role ofRAD52Epistasis Group Genes in Homologous Recombination and Double-Strand Break Repair
Authors: Symington Lorraine S. 
Published: January 2003

SUMMARYThe process of homologous recombination is a major DNA repair pathway that operates on DNA double-strand breaks, and possibly other kinds of DNA lesions, to promote error-free repair. Central to the process of homologous recombination are the RAD52 group genes (RAD50, RAD51, RAD52, RAD54, RDH54/TID1, RAD55, RAD57, RAD59, MRE11, and XRS2), most of which were identified by their requirement for the repair of ionizing-radiation-induced DNA damage in Saccharomyces cerevisiae. The Rad52 group proteins are highly conserved among eukaryotes, and Rad51, Mre11, and Rad50 are also conserved in prokaryotes and archaea. Recent studies showing defects in homologous recombination and double-strand break repair in several human cancer-prone syndromes have emphasized the importance of this repair pathway in maintaining genome integrity. Although sensitivity to ionizing radiation is a universal feature of rad52 group mutants, the mutants show considerable heterogeneity in different assays for recombinational repair of double-strand breaks and spontaneous mitotic recombination. Herein, I provide an overview of recent biochemical and structural analyses of the Rad52 group proteins and discuss how this information can be incorporated into genetic studies of recombination.
Regulation of Bacterial Drug Export Systems
Authors: Grkovic Steve , Brown Melissa H. , Skurray Ronald A. 
Published: January 2003

SUMMARY
The active transport of toxic compounds by membrane-bound efflux proteins is becoming an increasingly frequent mechanism by which cells exhibit resistance to therapeutic drugs. This review examines the regulation of bacterial drug efflux systems, which occurs primarily at the level of transcription. Investigations into these regulatory networks have yielded a substantial volume of information that has either not been forthcoming from or complements that obtained by analysis of the transport proteins themselves. Several local regulatory proteins, including the activator BmrR from Bacillus subtilis and the repressors QacR from Staphylococcus aureus and TetR and EmrR from Escherichia coli, have been shown to mediate increases in the expression of drug efflux genes by directly sensing the presence of the toxic substrates exported by their cognate pump. This ability to bind transporter substrates has permitted detailed structural information to be gathered on protein-antimicrobial agent-ligand interactions. In addition, bacterial multidrug efflux determinants are frequently controlled at a global level and may belong to stress response regulons such as E. coli mar, expression of which is controlled by the MarA and MarR proteins. However, many regulatory systems are ill-adapted for detecting the presence of toxic pump substrates and instead are likely to respond to alternative signals related to unidentified physiological roles of the transporter. Hence, in a number of important pathogens, regulatory mutations that result in drug transporter overexpression and concomitant elevated antimicrobial resistance are often observed.
Biochemistry and Comparative Genomics of SxxK Superfamily Acyltransferases Offer a Clue to the Mycobacterial Paradox: Presence of Penicillin-Susceptible Target Proteins versus Lack of Efficiency of Penicillin as Therapeutic Agent
Authors: Goffin Colette , Ghuysen Jean-Marie 
Published: January 2003

SUMMARY

The bacterial acyltransferases of the SxxK superfamily vary enormously in sequence and function, with conservation of particular amino acid groups and all-α and α/β folds. They occur as independent entities (free-standing polypeptides) and as modules linked to other polypeptides (protein fusions). They can be classified into three groups. The group I SxxK
d
,
d
-acyltransferases are ubiquitous in the bacterial world. They invariably bear the motifs SxxK, SxN(D), and KT(S)G. Anchored in the plasma membrane with the bulk of the polypeptide chain exposed on the outer face of it, they are implicated in the synthesis of wall peptidoglycans of the most frequently encountered (4→3) type. They are inactivated by penicillin and other β-lactam antibiotics acting as suicide carbonyl donors in the form of penicillin-binding proteins (PBPs). They are components of a morphogenetic apparatus which, as a whole, controls multiple parameters such as shape and size and allows the bacterial cells to enlarge and duplicate their particular pattern. Class A PBP fusions comprise a glycosyltransferase module fused to an SxxK acyltransferase of class A. Class B PBP fusions comprise a linker, i.e., protein recognition, module fused to an SxxK acyltransferase of class B. They ensure the remodeling of the (4→3) peptidoglycans in a cell cycle-dependent manner. The free-standing PBPs hydrolyze
d
,
d
peptide bonds. The group II SxxK acyltransferases frequently have a partially modified bar code, but the SxxK motif is invariant. They react with penicillin in various ways and illustrate the great plasticity of the catalytic centers. The secreted free-standing PBPs, the serine β-lactamases, and the penicillin sensors of several penicillin sensory transducers help the
d
,
d
-acyltransferases of group I escape penicillin action. The group III SxxK acyltransferases are indistinguishable from the PBP fusion proteins of group I in motifs and membrane topology, but they resist penicillin. They are referred to as Pen
r
protein fusions. Plausible hypotheses are put forward on the roles that the Pen
r
protein fusions, acting as
l
,
d
-acyltransferases, may play in the (3→3) peptidoglycan-synthesizing molecular machines. Shifting the wall peptidoglycan from the (4→3) type to the (3→3) type could help Mycobacterium tuberculosis and Mycobacterium leprae survive by making them penicillin resistant.
A rational approach to uninvestigated dyspepsia in primary care: review of the literature
Authors: Arents N L A , Thijs J C , Kleibeuker J H 
Published: January 2003

AbstractIn this paper the rationale and limitations of the four most important approach strategies to dyspepsia in primary care (empiric treatment, prompt endoscopy, “test-and-scope”, and “test-and-treat”) are analysed. It is concluded that in the absence of alarm symptoms, a “test-and-treat” approach is currently the most rational approach provided that three conditions are met: (1) a highly accurate test should be used, (2) the prevalence of Helicobacter pylori in the population should not be too low, and (3) an effective anti-H pylori regimen should be prescribed taking sufficient time to instruct and motivate the patient.
Management of motor neurone disease
Authors: Howard R S , Orrell R W 
Published: January 2003

Abstract
Motor neurone disease is a progressive neurodegenerative disorder leading to severe disability and death. It is clinically characterised by mixed upper and lower motor neurone involvement affecting bulbar, limb, and respiratory musculature. Recent guidelines have established diagnostic criteria and defined management of the condition. In a proportion of familial amyotrophic lateral sclerosis there is a mutation in the gene encoding the enzyme copper/zinc superoxide dismutase 1; this has allowed mutation screening and generated considerable laboratory based research. The diagnosis must be given with care and consideration and close follow up is essential. Management involves a multidisciplinary team based in the hospital and the community. Riluzole is the only drug shown to have a disease modifying effect and has been approved by the National Institute for Clinical Excellence. The essence of care is good symptomatic management, including nutritional support with percutaneous endoscopic gastrostomy and ventilatory care with non-invasive ventilation. Palliative care should be introduced before the terminal stages after careful discussion with the patient and carers. Knowledge of this condition has grown dramatically recently with a parallel improvement in treatment and ability to deal with the most troublesome problems.
An algorithm for the investigation and management of patients with suspected deep venous thrombosis at a district general hospital
Authors: Walsh K , Kelaher N , Long K , Cervi P 
Published: January 2003

Abstract
The aim was to show that clinical assessment and serial Dopplers could be used to exclude deep venous thrombosis (DVT), and also that clinical assessment in combination with D-dimers could be used to exclude DVT. This was a prospective trial. Patients underwent clinical assessment, colour flow Doppler, and D-dimer measurement. Patients with an equivocal first Doppler and patients with a moderate/high pre-test clinical score had a repeat Doppler. Follow up information was obtained to see if further thromboembolism developed. Outcome measures included the reliability of the clinical assessment, Doppler, and D-dimer in excluding DVT. One hundred and ninety four patients were enrolled. The negative predictive value of a low medical pre-test score in excluding DVT was 92%. Eighty eight patients underwent D-dimer measurement. The negative predictive value of a D-dimer &lt;400 units was 96%. The negative predictive value of a low clinical pre-test score and D-dimer &lt;400 units was 100%. The negative predictive value of a low clinical pre-test score and D-dimer &lt;800 units was 97%. The negative predictive value of the combination of a low clinical pre-test score and D-dimer &lt;400 units was 100%. Twenty three per cent of patients had a low clinical pre-test score and D-dimer &lt;400 units. Thus, a DVT could be excluded in 23% of referred patients. This information could be used to reduce Doppler requests by 23%. No patient in whom clinical assessment and serial Dopplers had excluded a DVT suffered further thromboembolism on follow up. This study has thus shown that a low medical pre-test score and negative Doppler reliably exclude DVT; a low pre-test score and negative D-dimer would reliably exclude DVT.
Dorsalis pedis arterial pulse: palpation using a bony landmark
Authors: Mowlavi A , Whiteman J , Wilhelmi B J , Neumeister M W , McLafferty R 
Published: January 2003

Abstract

Introduction
The unreliability of the pulse examination of the foot has primarily been due to variability of technique between examiners. Whereas the groove between the medial malleolus and the Achilles tendon more readily defines the location of the posterior tibial pulse, the location of the dorsalis pedis pulse remains vague. In this paper a novel method of locating the dorsalis pedis pulse by physical examination is described.

Methods
Forty one consecutive patients admitted to a general surgery service of a tertiary medical centre within a two month period were examined. Using the dorsal most prominence of the navicular bone as a landmark, the distance to the dorsalis pedis pulse in bilateral lower extremities was measured by palpation and compared to Doppler ultrasound. Measurements were confirmed by two separate examiners blinded to each others’ results.

Results
The dorsalis pedis artery was palpable in 78% of extremities and present by Doppler ultrasound in 95%. The location of the left dorsalis pedis artery was a mean (SD) 9.8 (1.4) mm by palpation and 11.1 (2.1) mm by Doppler ultrasound from the dorsal most prominence of the navicular bone. The right dorsalis pedis artery was 10.4 (3.4) mm by palpation and 11.5 (0.7) mm from the dorsal most prominence of the navicular bone. No significant differences in location of the dorsalis pedis artery were observed bilaterally between Doppler ultrasound and palpation; No significant differences were observed comparing contralateral dorsalis pedis arteries nor any differences between the examiners’ results.

Conclusion
The dorsal most prominence of the navicular bone provides a bony landmark to readily locate the dorsalis pedis artery. Reliability of the examination may be increased as to the patency of the dorsalis pedis artery by using this dependable anatomic landmark.
Guidelines, compliance, and effectiveness: a 12 months’ audit in an acute district general healthcare trust on the two week rule for suspected colorectal cancer
Authors: Debnath D , Dielehner N , Gunning K A 
Published: January 2003

Abstract

Objectives
The Department of Health had recently introduced guidelines so that all suspected colorectal cancer patients could be seen by a specialist within two weeks of referral by their general practitioners. The usefulness and practicality of such a decision had been questioned. The aims of this study were to measure the compliance to the guidelines and evaluate the effectiveness of such referrals.

Methods
All patients who were referred to the rapid access colorectal clinic between August 2000 and July 2001 were included.

Settings
Darlington Memorial Hospital and Bishop Auckland General Hospital, both under South Durham Health Care Trust, were considered for the study.

Measures
Date of referral, referring practitioner, time of appointment, reasons for referral, and diagnosis.

Results
A total of 239 referrals were made; 96.2% of patients were given appointments within two weeks. Rectal bleed was the commonest (32%) cause for referral. Diverticular disease was the most frequent (29%) condition diagnosed. Altogether 97.4% of referrals were incomplete and 37.6% did not comply with the guidelines. Twenty one colorectal cancers (8.9%) were diagnosed. The early cancer detection rate was 4.6%.

Conclusions
This audit showed that compliance to the guidelines was associated with a higher cancer detection rate. The majority of patients received appointments within two weeks. Contrary to some speculations, the number of referrals was not limitless. However a high number of referrals failed to adhere to the guidelines. The cancer (particularly early cancer) detection rate was disappointingly low. This does not reflect an efficient system of referral and potential benefits to patients remain questionable.
Epidemiology, public health and the problem of personality disorder
Authors: Coid Jeremy 
Published: January 2003

BackgroundThe public health problem-solving paradigm is a comprehensive method not previously applied to preventive interventions for personality disorder.AimsTo present an overview for clinical psychiatrists.MethodReview of epidemiological research into DSM–IV Axis II disorders and application to the paradigm.ResultsPersonality disorder affects a substantial proportion of the population. Burdens on health care, social and criminal justice agencies have yet to be accurately quantified. Debates continue over case definition, but there is increasing information on prevalence using ‘broad’ definitions and aetiology. A conceptual framework, based on development, suggests preventive interventions should be targeted in childhood. The public health approach also requires monitoring of risk factors operating at the population level.ConclusionsServices in England and Wales for persons with personality disorder are currently inadequate. The problem-solving paradigm suggests new preventive interventions. Psychiatrists should renegotiate their relationship with policy-makers and reconsider their preventive role.
Combining depot antipsychotic medications with novel antipsychotics in forensic patients: a practice in search of a principle
Authors: Bains Jatinder J. S. , Nielssen Olav B. 
Published: January 2003

OBJECTIVEWe observed a pattern of combining depot antipsychotic medication with the newer ‘atypical’ antipsychotics in forensic patients. We aimed to determine the prevalence and rationale for such ‘combination therapy’.METHODThe medical records of forensic patients in 3 forensic hospitals in New South Wales, Australia, were reviewed and the responsible psychiatrists asked to explain the rationale for treatment of those patients on combination therapy.ResultsTwenty-two per cent of the forensic patient population were receiving combination therapy. The reasons given for combination therapy were the presence of treatment-resistant illness, to ensure adherence to at least part of the treatment and to assist transfer to lower security units.CONCLUSIONSSuch a high prevalence of a practice that is discouraged and without theoretical justification is a cause for concern. It appeared to reflect the practical difficulties of managing forensic patients.
Descriptive study of the effects of altering formulation of prescribed methadone from injectable to oral
Authors: Myton Tracey , Fletcher Keron 
Published: January 2003

Aims and MethodTo describe an enforced but gentle transition from prescribed intravenous methadone to oral methadone in 14 opiate-dependent patients. We examined their case notes looking for ease of transition, evidence of illicit drug use before and during the 6 months following transition and progress 3 years later.ResultsEight patients immediately stopped injecting, the remainder used intravenous heroin in addition to prescribed oral methadone for some months. There were no serious adverse events. Three years later, four patients had ceased opiate use altogether and six were maintained on oral methadone (five of these without illicit use). Two patients were prescribed oral methadone by their general practitioner and one was no longer in treatment.Clinical ImplicationsWe show that it is possible to alter the formulation of prescribed methadone without deterioration in clinical stability or losing patients from treatment. This is an important conclusion as it is presumed that one of the aims of treatment with intravenous methadone is to move patients away from injectable to oral use. Offering patients a transition period of 6 months and a choice of the process of transition may be helpful.