CD and NMR studies on the conformational thermostability of 2-thioribothymidine found in the TψC loop of thermophile tRNA

Watanabe, Kimitsuna; Yokoyama, Shigeyuki; Hansske, Fritz; Kasai, Hiroshi; Miyazawa, Tatsuo

doi:10.1016/0006-291x(79)91574-2

Cited by 45 publications

(39 citation statements)

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“…The effects of certain posttranscriptional modifications on specific tRNA functions, such as enforcement of correct codon recognition (59), and on the structural stability of RNA (26,28,54,55) have been well documented. Further, it is known tRNA molecules completely lacking modified nucleosides do not adopt the native conformation without compensation from high magnesium concentrations (20).…”

Section: Discussionmentioning

confidence: 99%

“…The role of posttranscriptionally modified nucleosides in RNA of thermophilic bacteria (54,55) and archaea (26,28) in enforcing conformational stability of RNA has been documented. By contrast, there is no extant literature on the extent of posttranscriptional modification of any RNA in psychrophilic microorganisms or whether specific modified nucleosides are produced in the RNA of these organisms to preserve biological activity and structural integrity at low temperature.…”

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Posttranscriptional modification of tRNA in psychrophilic bacteria

et al. 1997

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Posttranscriptional modification in tRNA is known to play a multiplicity of functional roles, including maintenance of tertiary structure and cellular adaptation to environmental factors such as temperature. Nucleoside modification has been studied in unfractionated tRNA from three psychrophilic bacteria (ANT-300 and Vibrio sp. strains 5710 and 29-6) and one psychrotrophic bacterium (Lactobacillus bavaricus). Based on analysis of total enzymatic hydrolysates by liquid chromatography-mass spectrometry, unprecedented low amounts of modification were found in the psychrophiles, particularly from the standpoint of structural diversity of modifications observed. Thirteen to 15 different forms of posttranscriptional modification were found in the psychrophiles, and 10 were found in L. bavaricus, compared with approximately 29 known to occur in bacterial mesophiles and 24 to 31 known to occur in the archaeal hyperthermophiles. The four most abundant modified nucleosides in tRNA from each organism were dihydrouridine, pseudouridine, 7-methylguanosine, and 5-methyluridine. The molar abundances of the latter three nucleosides were comparable to those found in tRNA from Escherichia coli. By contrast, the high levels of dihydrouridine observed in all three psychrophiles are unprecedented for any organism in any of the three phylogenetic domains. tRNA from these organisms contains 40 to 70% more dihydrouridine, on average, than that of the mesophile E. coli or the psychrotroph L. bavaricus. This finding supports the concept that a functional role for dihydrouridine is in maintenance of conformational flexibility of RNA, especially important to organisms growing under conditions where the dynamics of thermal motion are severely compromised. This is in contrast to the role of modifications contained in RNA from thermophiles, which is to reduce regional RNA flexibility and provide structural stability to RNA for adaptation to high temperature.The structural diversity (31) and multiplicity of roles played by posttranscriptional modification in RNA, particularly tRNA (3, 4, 59), has been clearly established. Despite the fact that 80 different modified nucleosides are presently known (8) to occur in tRNA from organisms representing all three phylogenetic domains (31), nearly all knowledge of posttranscriptional modification in RNA is derived from studies of mesophiles and thermophiles. Of 521 reported tRNA sequences (46), the only apparent exception is the initiator tRNA from the arthropod Euphausia sperba, which inhabits the Antarctic Sea (52). We are unaware of previous investigations reporting modification in tRNA from any psychrophilic microorganism, despite the fact that greater than 80% of the biosphere is characterized by temperatures below 5ЊC. Nevertheless, interest in these organisms and their biotechnological potential has increased substantially in recent years (25, 32), and they represent a fundamentally important but understudied segment of the biosphere. Psychrophilic microorganisms have an optimum temperature for g...

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Section: Discussionmentioning

confidence: 99%

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Posttranscriptional modification of tRNA in psychrophilic bacteria

et al. 1997

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“…The vicinal coupling constants of s2dT and dT are listed in table 2, together with those of s2T and T as in [3]. The fractional populations of the C3 ' -endo and C2' -endo forms of the ribose ring may be obtained as J3,4,/(Jr,2, + J3'4') and Ji,21/(Ji121 + J~!.P), respectively, and the populations of the gg, gt and tg forms have been obtained from J4<5' and J4151 I by the standard method [6] (table 2).…”

Section: Conformation Of Ribose Moietymentioning

confidence: 99%

“…This modification ps2T] has been found to cont~bute to the the~ostability of extreme thermophile tRNAs [1,2]. For elucidating the molecular mechanism of such thermostability of tRNAs, we have studied the conformational characteristics of s2T in comparison with T [3]. By proton NMR analyses, we have found that the ribose moiety of $1: predominantly takes the C3 ' -endo-gg form and the enthalpy difference between the C2' and C3 ' -endo forms is much larger in sZT (1 .O kcal .…”

Section: F Introductionmentioning

confidence: 99%

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NMR analyses on the molecular mechanism of the conformational rigidity of 2‐thioribothymidine, a modified nucleoside in extreme thermophile tRNAs

et al. 1983

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'H-NMR analyses have been made on the conformations of Zthioribothymidine (s2T), 2-thiodeoxyribothyrnidine (s2dT), as well as ribothymidine (T) and deoxyribothymidine (dT). s2T and s2dT exclusively take the anti form rather than the syn form. The C3 ' -endo-gg form of the sugar moiety is remarkably stabilized on modification of T to s2T, but not on m~ifi~tion of dT to s2dT. The steric effects of the 2-~ioc~bonyl group and the 2'-hydroxyl group cause the rigidity of the C3'-endo-gg form of s2T. Such rigidity of s% probably contributes to the thermostability of 2-thiopyrimidine polyribonucleotides and extreme thermophile tRNAs.tRNA Extreme thermophile Thermostability NMR 2-Thiopyrimidine polyribonucleotide 2-Thioribothymidine

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Economic evaluation of a diabetes disease management programme with a central role for the diabetes nurse specialist

Steuten

Bruijsten

Vrijhoef

2007

European Diabetes Nursing

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Background: In the region of Maastricht, The Netherlands, a disease management programme (DMP) for patients with diabetes mellitus was implemented. The programme aims to improve quality of care within existing budgets. To achieve this, diabetes nurse specialists (DNSs) were given a central role within a multidisciplinary team of care providers. This study describes the cost-effectiveness of this approach. Aim: To measure the incremental cost-effectiveness of a diabetes DMP, with a central role for the diabetes nurse specialist, in comparison to usual diabetes care. Methods: Within the DMP, patients with low, medium and high complexities of care are cared for by general practitioners, DNSs and endocrinologists, respectively. The DNSs independently treat patients assigned to them and pay special attention to extensive self-management education. A quasi-experimental trial with two-year follow-up (n=473) was undertaken to measure the cost-effectiveness of the DMP compared with usual care. Results: A total of 23% of patients were assigned to the GP, 66% to the DNS and 10% to the endocrinologist. Statistical significant improvements in glycaemic control, health-related quality of life, compliance and most aspects of self-care behaviour were found. No statistically significant changes were found concerning total costs of care. All improvements were greatest in patients assigned to DNS. Conclusion: A DMP in which DNSs play a central role is associated with improved quality of care within existing budgets. Patients assigned to DNS benefit most, indicating that the central role of DNS in the diabetes DMP is one of its critical success factors.Eur Diabetes Nursing 2007; 4(2): 64-71. Key WordsDiabetes nurse specialist; multidisciplinary team; disease management programme; economic evaluation February 2002, patients were recruited from a convenience sample of nine randomly chosen general practices (involving 12 GPs) and the hospital's outpatient department; they were followed for 24 months. Subsequently, patients with a diagnosis of diabetes mellitus and aged ≥16 years were invited to participate. Since the DMP aimed to cover the entire population of people with diabetes (including patients with complications and/or co-morbidity), only patients with severe co-morbidity, such as pre-terminal renal failure or carcinoma and/or those needing dialysis, were excluded. Authors Study designA single-group pre-post test design was applied, 18 since the DMP was implemented region-wide and a 'fair' comparison region was unavailable. In all potential comparison regions, innovations that would bias the measure of usual care, such as self-management programmes or electronic patient record devices, were being implemented. Disease management programmeThe DMP involves all patients with type 1 or 2 diabetes mellitus who are known by the GP. The main features of the DMP are: use of evidencebased guidelines; central co-ordination of care; assignment of patients to a care provider; and central data collection with annual individual feedbac...

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CD and NMR studies on the conformational thermostability of 2-thioribothymidine found in the TψC loop of thermophile tRNA

Cited by 45 publications

References 17 publications

Posttranscriptional modification of tRNA in psychrophilic bacteria

Posttranscriptional modification of tRNA in psychrophilic bacteria

NMR analyses on the molecular mechanism of the conformational rigidity of 2‐thioribothymidine, a modified nucleoside in extreme thermophile tRNAs

Economic evaluation of a diabetes disease management programme with a central role for the diabetes nurse specialist

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