bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Global Responses of
Mycobacterium tuberculosis
to Physiological Levels of Copper
Authors: Ward Sarah K. , Hoye Elizabeth A. , Talaat Adel M. 
Published: February 2008

ABSTRACT

Copper (Cu) is a required micronutrient, but it is highly toxic at high concentrations. Therefore, the levels of Cu must be tightly regulated in all living cells. The phagosome of
Mycobacterium tuberculosis
has been shown to have variable levels of Cu. Previously, we showed that
M. tuberculosis
contains a copper-sensitive operon,
cso
, that is induced during early infection in mice. In this study, we showed that
ctpV
, a gene in the
cso
operon, is a copper-responsive gene and most likely encodes an efflux pump for Cu. Furthermore, the transcription of key genes in the
cso
operon is induced by Cu ions and not by other ions, such as Ni and Zn ions. To elucidate copper-responsive genes other than those in the
cso
operon, we utilized DNA microarrays to profile mycobacterial responses to physiological levels of Cu. A transcriptome analysis identified a novel set of 30 copper-responsive genes in
M. tuberculosis
, one-half of which were induced only when toxic levels of Cu were added. Interestingly, several transcriptional regulators, including the
furA
gene, were induced during toxic Cu exposure, indicating that there was a generalized response to oxidative stressors rather than a Cu-specific response. In general, the Cu-induced transcriptome generated should help elucidate the role of the Cu response in maintaining
M. tuberculosis
survival during infection and could provide novel targets for controlling this virulent pathogen.
TrpY Regulation of
trpB2
Transcription in
Methanothermobacter thermautotrophicus
Authors: Karr Elizabeth A. , Sandman Kathleen , Lurz Rudi , Reeve John N. 
Published: February 2008

ABSTRACT

TrpY binds specifically to TRP box sequences upstream of
trpB2
, but the repression of
trpB2
transcription requires additional TrpY assembly that is stimulated by but not dependent on the presence of tryptophan. Inhibitory complex formation is prevented by insertions within the regulatory region and by a G149R substitution in TrpY, even though TrpY(G149R) retains both TRP box DNA- and tryptophan-binding abilities.
Acetamido Sugar Biosynthesis in the Euryarchaea
Authors: Namboori Seema C. , Graham David E. 
Published: February 2008

ABSTRACT

Archaea and eukaryotes share a dolichol phosphate-dependent system for protein N-glycosylation. In both domains, the acetamido sugar
N
-acetylglucosamine (GlcNAc) forms part of the core oligosaccharide. However, the archaeal
Methanococcales
produce GlcNAc using the bacterial biosynthetic pathway. Key enzymes in this pathway belong to large families of proteins with diverse functions; therefore, the archaeal enzymes could not be identified solely using comparative sequence analysis. Genes encoding acetamido sugar-biosynthetic proteins were identified in
Methanococcus maripaludis
using phylogenetic and gene cluster analyses. Proteins expressed in
Escherichia coli
were purified and assayed for the predicted activities. The MMP1680 protein encodes a universally conserved glucosamine-6-phosphate synthase. The MMP1077 phosphomutase converted α-
d
-glucosamine-6-phosphate to α-
d
-glucosamine-1-phosphate, although this protein is more closely related to archaeal pentose and glucose phosphomutases than to bacterial glucosamine phosphomutases. The thermostable MJ1101 protein catalyzed both the acetylation of glucosamine-1-phosphate and the uridylyltransferase reaction with UTP to produce UDP-GlcNAc. The MMP0705 protein catalyzed the C-2 epimerization of UDP-GlcNAc, and the MMP0706 protein used NAD
+
to oxidize UDP-
N
-acetylmannosamine, forming UDP-
N
-acetylmannosaminuronate (ManNAcA). These two proteins are similar to enzymes used for proteobacterial lipopolysaccharide biosynthesis and gram-positive bacterial capsule production, suggesting a common evolutionary origin and a widespread distribution of ManNAcA. UDP-GlcNAc and UDP-ManNAcA biosynthesis evolved early in the euryarchaeal lineage, because most of their genomes contain orthologs of the five genes characterized here. These UDP-acetamido sugars are predicted to be precursors for flagellin and S-layer protein modifications and for the biosynthesis of methanogenic coenzyme B.
Dual Role of LldR in Regulation of the
lldPRD
Operon, Involved in
l
-Lactate Metabolism in
Escherichia coli
Authors: Aguilera Laura , Campos Evangelina , Giménez Rosa , Badía Josefa , Aguilar Juan , Baldoma Laura 
Published: February 2008

ABSTRACT

The
lldPRD
operon of
Escherichia coli
, involved in
l
-lactate metabolism, is induced by growth in this compound. We experimentally identified that this system is transcribed from a single promoter with an initiation site located 110 nucleotides upstream of the ATG start codon. On the basis of computational data, it had been proposed that LldR and its homologue PdhR act as regulators of the
lldPRD
operon. Nevertheless, no experimental data on the function of these regulators have been reported so far. Here we show that induction of an
lldP-lacZ
fusion by
l
-lactate is lost in an Δ
lldR
mutant, indicating the role of LldR in this induction. Expression analysis of this construct in a
pdhR
mutant ruled out the participation of PdhR in the control of
lldPRD
. Gel shift experiments showed that LldR binds to two operator sites, O1 (positions −105 to −89) and O2 (positions +22 to +38), with O1 being filled at a lower concentration of LldR.
l
-Lactate induced a conformational change in LldR that did not modify its DNA binding activity. Mutations in O1 and O2 enhanced the basal transcriptional level. However, only mutations in O1 abolished induction by
l
-lactate. Mutants with a change in helical phasing between O1 and O2 behaved like O2 mutants. These results were consistent with the hypothesis that LldR has a dual role, acting as a repressor or an activator of
lldPRD
. We propose that in the absence of
l
-lactate, LldR binds to both O1 and O2, probably leading to DNA looping and the repression of transcription. Binding of
l
-lactate to LldR promotes a conformational change that may disrupt the DNA loop, allowing the formation of the transcription open complex.
Robert Boyle's 'Designe about Natural History'
Authors: Hunter Michael , Anstey Peter 
Published: February 2008

AbstractThis paper provides an analysis of Robert Boyle's most detailed discussion of the Baconian method of natural history. In a long letter to Henry Oldenburg dated 13 June 1666 and in ancillary manuscript material, Boyle spells out the method or 'Designe' by which he believes experimental programs in natural philosophy should be written up. The 'Designe' is enormously important in giving a clear statement of the precise contours of Boyle's Baconian methodology and providing a key to understanding the rationale, composition and format for many of his published histories. Works such as New Experiments and Considerations Touching Cold, Memoirs for the Natural History of Human Blood and even his more speculative writings such as An Introduction to the History of Particular Qualities are best understood in terms of Boyle's overall method as articulated in his “Designe about Natural History”.
The RAST Server: Rapid Annotations using Subsystems Technology
Authors: Aziz Ramy K , Bartels Daniela , Best Aaron A , DeJongh Matthew , Disz Terrence , Edwards Robert A , Formsma Kevin , Gerdes Svetlana , Glass Elizabeth M , Kubal Michael , Meyer Folker , Olsen Gary J , Olson Robert , Osterman Andrei L , Overbeek Ross A , McNeil Leslie K , Paarmann Daniel , Paczian Tobias , Parrello Bruce , Pusch Gordon D , Reich Claudia , Stevens Rick , Vassieva Olga , Vonstein Veronika , Wilke Andreas , Zagnitko Olga 
Published: February 2008

Abstract

Background
The number of prokaryotic genome sequences becoming available is growing steadily and is growing faster than our ability to accurately annotate them.

Description
We describe a fully automated service for annotating bacterial and archaeal genomes. The service identifies protein-encoding, rRNA and tRNA genes, assigns functions to the genes, predicts which subsystems are represented in the genome, uses this information to reconstruct the metabolic network and makes the output easily downloadable for the user. In addition, the annotated genome can be browsed in an environment that supports comparative analysis with the annotated genomes maintained in the SEED environment.
The service normally makes the annotated genome available within 12–24 hours of submission, but ultimately the quality of such a service will be judged in terms of accuracy, consistency, and completeness of the produced annotations. We summarize our attempts to address these issues and discuss plans for incrementally enhancing the service.

Conclusion
By providing accurate, rapid annotation freely to the community we have created an important community resource. The service has now been utilized by over 120 external users annotating over 350 distinct genomes.
Splenic rupture after colonoscopy: Report of a case and review of literature
Authors: Cappellani Alessandro , Di Vita Maria , Zanghì Antonio , Cavallaro Andrea , Alfano Giovanni , Piccolo Gaetano , Lo Menzo Emanuele 
Published: February 2008

Abstract
Splenic rupture is a rare complication of colonoscopy. For this reason the diagnosis could be delayed and the outcome dismal. Fifty-four cases of splenic rupture after colonoscopy have been described in the literature. The majority of the cases required emergent or delayed splenectomy, 13 of these cases were treated conservatively. The main feature that stands out from the review of the literature is the "surprise" of this unexpected complication. This factor explains the elevated mortality (2 out of 54 cases), likely due to the delay in diagnosis. The case here described is probably among the most complex published in the literature; in fact the presence of dense intra-abdominal adhesions not only contributed to the complication itself, but also explain the confinement of the hemoperitoneum to the left supra-mesocolic space and the delayed presentation (13 days from the time of the trauma).
A Confucian perspective on bioethical principles in ethics consultation
Authors: Tai MC , Hill D 
Published: February 2008

With the rapid development of biotechnology, the physician is now more able to keep a patient's life going indefinitely on a life support system. The question of whether we should switch off the machine often arises when, according to the medical prognosis, there is no hope of recovery, or in a no-win situation where you are 'damned if you do and damned if you don't'. In a case which seems without hope, the dilemma of whether to prolong a life or let it go disturbs many people, including health professionals as well as the family of the patient. In this painful situation, an ethics consultant who has received intensive training can help the concerned parties to arrive at what may be the best decision. How do Asians, especially those living in countries influenced by Confucian teachings, reach their answers? Three aspects are usually considered: (1) motivation and situation; (2) reasonableness and propriety; and (3) lawfulness and legality. More specifically, three questions are deliberated, as follows. (1) Where an action has already been taken, what motivated it and in what situation? Or, where a decision has still to be made, what should motivate it, and what are the relevant features of the situation? (2) Was the attempted resolution of the dilemma, or is its prospective resolution, reasonable and in accordance with traditional principles of ethical behaviour? (3) Was the action taken lawful, or would the intended action be lawful? This approach to finding an answer has been practised for centuries in Confucian society. But what is legal may not always be reasonable, what is reasonable may not always be compassionate, and what is compassionate may not always be either legal or reasonable. Principles to guide decision-making are therefore called for. This article, written by Michael Cheng-tek Tai in collaboration with Donald Hill, discusses the Confucian method of solving a problem and examines its principal features and how they are applied in ethics consultations. The article is followed by a series of questions and answers and a commentary by Donald Hill.
Ethical issues in child protection
Authors: Larcher Vic 
Published: February 2008

The management of child protection concerns arouses strong emotions and controversies and creates ethical tensions for all concerned. This paper provides a rational analysis of some of the issues involved and suggests responses to them. The ethical and legal duties of health-care professionals are to act in the best interests of the child by safeguarding children and reporting concerns. But this may involve conflicts with parents and produce reluctance of professionals to become involved, especially in controversial types of abuse. Mandatory reporting of concerns might overcome such reluctance, but may be ineffective in the face of diagnostic uncertainties. Assembly of a stronger diagnostic evidence base would seem ethically justified, but organization of the necessary case controlled studies might be problematic. Even with a comprehensive evidence base, individual diagnoses of abuse will always involve value judgements that should be underpinned by effective training and assessment of core competencies of professionals. These manoeuvres are unlikely to prevent both justified and vexatious complaints, often in relation to breaches in professional duties or concerning professional misconduct. The tendency to blame experts may have contributed to a reluctance of other professionals to become involved, despite proposals for reforms in the expert witness and court systems. Current approaches to child protection may neither promote greater understanding nor be in the best interests of children. A revised social contract for the effective protection of children could include: a duty of care that adequately addresses the primacy of the child's welfare; the acquisition of a sound evidence base; professional transparency and accountability (but with protection from malicious and vexatious complaints); and a shift emphasis towards a more inquisitorial system that embraced the principles of truth and reconciliation.
Identification of L-plastin autoantibody in plasma of patients with non-Hodgkin's lymphoma using a proteomics-based analysis
Authors: Ueda Kazuhito , Nakanishi Toyofumi , Shimizu Akira , Takubo Takayuki , Matsuura Nariaki 
Published: February 2008

Background The diagnosis of malignant lymphoma (ML) such as non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL) was mainly performed by morphological examination and gene analysis. There are only a few serum/plasma biomarkers such as lactate dehydrogenase and soluble interleukin-2 receptor α to diagnose ML. The classifications are various, and therefore the cell surface markers using flow cytometry or lymph node biopsy have been examined. It is difficult, however, to distinguish the two diseases, NHL and HL, from each other. Methods In order to identify the haematological malignancy-associated autoimmunoreactivity (autoantibodies) in patients' plasma, a novel proteomics-based approach using electrophoresis/mass spectrometry was applied. Solubilized proteins from a Burkitt's lymphoma cell line (Raji) were separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and Western blotting analysis, in which the plasma of individual patients with haematological malignancies was tested for primary antibodies, followed by visualization with anti-IgG antibody conjugated with horseradish peroxidase. Results Two proteins, L-plastin and α-enolase, capable of reacting with the antibodies in plasma of patients with NHL, were detected using matrix-assisted laser desorption ionization/time-of-flight mass spectrometry and tandem mass spectrometry. The rates of the detections of an anti L-plastin autoantibody were significantly higher: 0.84 (21/25) in patients with NHL; 0.00 (0/4) in HL; 0.38 (5/13) in autoimmune diseases; 0.20 (2/10) in leukaemia; and 0.13 (1/8) in healthy controls. In contrast, those of anti α-enolase antibody were not specific to NHL. Conclusions We first identified autoantibody against L-plastin in plasma of patients with NHL, suggesting that the autoantibody can be a new diagnostic biomarker for NHL.
Altered red cell membrane compositions related to functional vitamin B12 deficiency manifested by elevated urine methylmalonic acid concentrations in patients with schizophrenia
Authors: Özcan Ömer , İpçioğlu Osman Metin , Gültepe Mustafa , Başoğlu Cengiz 
Published: February 2008

Background Abnormal cell membrane composition and functional cobalamin (vitamin B12) deficiency was reported in schizophrenic individuals. We aimed to investigate the relationship between cobalamin state and cell membrane composition in patients with schizophrenia. Methods Malondialdehyde (MDA), cholesterol, and phospholipid classes in the erythrocyte membranes of 18 schizophrenic and 20 healthy individuals of the same age and sex distribution were determined. Serum vitamin B12, plasma total homocysteine, serum folate, and urine methylmalonic acid (uMMA) concentrations were measured in both groups. Results In the schizophrenic group, uMMA, membrane MDA, membrane cholesterol, membrane phosphatidylinositol concentrations were significantly higher and the membrane phosphatidylserine concentrations were lower than the control group values. In schizophrenic individuals, uMMA concentrations have a significant positive correlation with membrane MDA and a negative correlation with membrane cholesterol concentrations ( P < 0.05). The negative correlation of uMMA with membrane cholesterol concentrations may be a biological response to the increased membrane rigidity. Also, a free radical elevation related to the elevated uMMA concentrations in the erythrocyte membrane, might reflect the role of methylmalonic acid (MMA) in membrane damage. Conclusion Our present findings suggest that, functional vitamin B12 deficiency representing itself by MMA elevations in schizophrenic individuals could damage cell membrane.
The commutability of external quality assurance serum and reference serum materials between the VITROS® Albumin Slide and four other routine albumin methods
Authors: Gould N , Møller J , Andrieux L 
Published: February 2008

Background Between-method differences in external quality assurance schemes (EQAS) are assumed to be indicative of between-method differences in results for fresh diagnostic serum samples. However, this assumption is only valid if the EQAS fluid is shown to be commutable between methods with the fresh human samples. Using fresh human serum samples, we studied the commutability of six UK National EQAS (UKNEQAS) samples and two reference serum preparations using five methods for the measurement of albumin. Methods The VITROS® Albumin Slide was compared with two liquid reagent bromocresol green-based methods and two immunoturbidimetric methods. Thirty fresh human serum samples, six UKNEQAS samples and two reference materials were analysed over a period of five days by all methods. The reference materials were: a certified protein reference material, CRM470 (protein reference preparation) and the Scandinavian NFKK Reference Serum X. Results A concentration-dependent tendency towards non-commutability was seen for the six UKNEQAS samples. Two of the methods recovered the CRM470 above the upper limit of the expected range and the remaining three were within the expected range. Conclusions Assessment of commutability is important in the investigation of between-method differences in EQAS. External quality assurance and reference materials should have been demonstrated to be commutable and be available at multiple concentrations, before they may be considered appropriate for the assessment of accuracy.
Measurement of breath hydrogen and methane, together with lactase genotype, defines the current best practice for investigation of lactose sensitivity
Authors: Waud Jonathan P , Matthews Stephanie B , Campbell Anthony K 
Published: February 2008

Background Currently, there is no ‘gold standard’ for detecting patients with sensitivity to lactose. Biochemical investigation by a breath hydrogen test alone detects <50% cases. Breath methane and symptoms are not recorded as standard practice. The clinical value of analysing C/T13910 and G/A22018 polymorphisms, strongly associated with lactose sensitivity, has not been established. Methods Two hundred and ten patients with unexplained gut and systemic symptoms and controls were challenged with 50 g lactose. Breath hydrogen and methane were measured and symptoms recorded. All were genotyped for two polymorphisms, C/T13910 and G/A22018. Results CC13910/GG22018 in 14.5%, CT13910/GA22018 in 39% and TT13910/AA22018 in 46.5%. One hundred percent of CC13910/GG22018 were lactose sensitive having a breath hydrogen >20 ppm within 6 h and symptoms. But the breath hydrogen test lacked sensitivity and specificity in the other groups. There was elevated breath hydrogen in 21% of CT13910/GA22018 and 15% of TT13910/AA22018 by 6 h, whereas 17 and 30.9% had elevated breath methane alone. Breath methane and breath hydrogen with clinical symptoms improved sensitivity and specificity, increasing detection of lactose sensitivity in genotypes CT/GA and TT/AA from <50 to >75%. Conclusions The data presented define the current best practice for the clinical identification of lactose sensitivity. Patients were first genotyped. Those identified as CC with symptoms should immediately undertake a 12-week lactose-free diet. Those identified as CT or TT should undertake a breath hydrogen and methane test. Those positive for hydrogen or methane along with symptoms or with symptoms only, should also undertake a lactose-free diet. Those with high hydrogen without symptoms should be investigated for causes other than lactose sensitivity.
A critical analysis of mini peer assessment tool (mini-PAT)
Authors: Abdulla Aza 
Published: February 2008

The structured evaluation of doctors’ performance through peer review is a relatively new phenomenon brought about by public demand for accountability to patients. Medical knowledge (as assessed by examination score) is no longer a good predictor of individual performance, humanistic qualities and communication skills. The process of peer review (or multi-source assessment) was developed over the last two decades in the USA and has started to pick up momentum in the UK through the introduction of Modernizing Medical Careers. However the concept is not new. Driven by market forces, it was initially developed by industrial organizations to improve leadership qualities with a view to increasing productivity through positive behaviour change and self-awareness. Multi-source feedback is not without its problems and may not always produce its desired outcomes. In this article we review the evidence for peer review and critically discuss the current process of mini peer assessment tool (mini-PAT) as the assessment tool for peer review employed in UK.