| 1. |
- Freyhult, Eva, et al.
(författare)
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Fisher: a program for the detection of H/ACA snoRNAs using MFE secondary structure prediction and comparative genomics - assessment and update
- 2008
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Ingår i: BMC Research Notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 1:49, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe H/ACA family of small nucleolar RNAs (snoRNAs) plays a central role in guiding the pseudouridylation of ribosomal RNA (rRNA). In an effort to systematically identify the complete set of rRNA-modifying H/ACA snoRNAs from the genome sequence of the budding yeast, Saccharomyces cerevisiae, we developed a program - Fisher - and previously presented several candidate snoRNAs based on our analysis [1]. FindingsIn this report, we provide a brief update of this work, which was aborted after the publication of experimentally-identified snoRNAs [2] identical to candidates we had identified bioinformatically using Fisher. Our motivation for revisiting this work is to report on the status of the candidate snoRNAs described in [1], and secondly, to report that a modified version of Fisher together with the available multiple yeast genome sequences was able to correctly identify several H/ACA snoRNAs for modification sites not identified by the snoGPS program [3]. While we are no longer developing Fisher, we briefly consider the merits of the Fisher algorithm relative to snoGPS, which may be of use for workers considering pursuing a similar search strategy for the identification of small RNAs. The modified source code for Fisher is made available as supplementary material. ConclusionOur results confirm the validity of using minimum free energy (MFE) secondary structure prediction to guide comparative genomic screening for RNA families with few sequence constraints.
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| 2. |
- Andriesse, Hanneke, et al.
(författare)
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Reliability and validity of motion analysis in children treated for congenital clubfoot according to the Clubfoot Assessment Protocol (CAP) using inexperienced assessors
- 2009
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Ingår i: BMC Research Notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Background. The Clubfoot Assessment Protocol (CAP) was developed for follow-up of children treated for clubfoot. The objective of this study was to analyze reliability and validity of the six items used in the domain CAPMotion Quality using inexperienced assessors. Findings. Four raters (two paediatric orthopaedic surgeons, two senior physiotherapists) used the CAP scores to analyze, on two different occasions, 11 videotapes containing standardized recordings of motion activity according to the domain CAPMotion Quality These results were compared to a criterion (two raters, well experienced CAP assessors) for validity and for checking for learning effect. Weighted kappa statistics, exact percentage observer agreement (Po), percentage observer agreement including one level difference (Po-1) and amount of scoring scales defined how reliability was to be interpreted. Inter- and intra rater differences were calculated using median and inter quartile ranges (IQR) on item level and mean and limits of agreement on domain level. Inter-rater reliability varied between fair and moderate (kappa) and had a mean agreement of 48/88% (Po/Po-1). Intra -rater reliability varied between moderate to good with a mean agreement of 63/96%. The intra- and inter-rater differences in the present study were generally small both on item (0.00) and domain level (-1.10). There was exact agreement of 51% and Po-1 of 91% of the six items with the criterion. No learning effect was found. Conclusion. The CAPMotion quality can be used by inexperienced assessors with sufficient reliability in daily clinical practice and showed acceptable accuracy compared to the criterion.
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| 3. |
- Benamer, Hani Ts, et al.
(författare)
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The Libyan doctors' brain drain: an exploratory study.
- 2009
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Ingår i: BMC Research Notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 2:Dec 8
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: Medical emigration from developing to developed countries is a well established phenomenon of substantial importance. Though Libya is classified as an upper-middle income country, it has been affected by this trend. This study was undertaken to identify some of the possible reasons behind the emigration of Libyan doctors and factors that might motivate them to return. FINDINGS: Seventy-four completed questionnaires were analysed. Median age of the respondents was 43 years (33-60) and median duration of stay outside Libya was 15 years (6-29). Most of the participants were resident in Europe (66%). The desire to further their education and research was the main reason given by 88% of the respondents for leaving Libya, while 50% of them gave that as the main reason for staying abroad. One-third of the respondents (31%) cited economic factors as the main reason for not returning. None of the respondents ruled out returning to Libya, and about half of them stated that they definitely or probably will return to Libya. 58% ranked reform of the Libyan health system as the most important reason that could induce them to return to Libya. CONCLUSION: The study shows that reforming the health care system in Libya might induce some of the physicians who moved abroad mainly for educational and economic reasons to return to Libya to practice medicine.
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| 4. |
- Pasupuleti, Mukesh, et al.
(författare)
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Antimicrobial activity of a C-terminal peptide from human extracellular superoxide dismutase
- 2009
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Ingår i: BMC research notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 2, s. 136-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Antimicrobial peptides (AMP) are important effectors of the innate immune system. Although there is increasing evidence that AMPs influence bacteria in a multitude of ways, bacterial wall rupture plays the pivotal role in the bactericidal action of AMPs. Structurally, AMPs share many similarities with endogenous heparin-binding peptides with respect to secondary structure, cationicity, and amphipathicity. FINDINGS: In this study, we show that RQA21 (RQAREHSERKKRRRESECKAA), a cationic and hydrophilic heparin-binding peptide corresponding to the C-terminal region of extracellular superoxide dismutase (SOD), exerts antimicrobial activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis and Candida albicans. The peptide was also found to induce membrane leakage of negatively charged liposomes. However, its antibacterial effects were abrogated in physiological salt conditions as well as in plasma. CONCLUSION: The results provide further evidence that heparin-binding peptide regions are multifunctional, but also illustrate that cationicity alone is not sufficient for AMP function at physiological conditions. However, our observation, apart from providing a link between heparin-binding peptides and AMPs, raises the hypothesis that proteolytically generated C-terminal SOD-derived peptides could interact with, and possibly counteract bacteria. Further studies are therefore merited to study a possible role of SOD in host defence.
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| 5. |
- Hedlund, Joel, et al.
(författare)
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BRICHOS - a superfamily of multidomain proteins with diverse functions.
- 2009
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Ingår i: BMC research notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 2, s. 180-
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: The BRICHOS domain has been found in 8 protein families with a wide range of functions and a variety of disease associations, such as respiratory distress syndrome, dementia and cancer. The domain itself is thought to have a chaperone function, and indeed three of the families are associated with amyloid formation, but its structure and many of its functional properties are still unknown. FINDINGS: The proteins in the BRICHOS superfamily have four regions with distinct properties. We have analysed the BRICHOS proteins focusing on sequence conservation, amino acid residue properties, native disorder and secondary structure predictions. Residue conservation shows large variations between the regions, and the spread of residue conservation between different families can vary greatly within the regions. The secondary structure predictions for the BRICHOS proteins show remarkable coherence even where sequence conservation is low, and there seems to be little native disorder. CONCLUSIONS: The greatly variant rates of conservation indicates different functional constraints among the regions and among the families. We present three previously unknown BRICHOS families; group A, which may be ancestral to the ITM2 families; group B, which is a close relative to the gastrokine families, and group C, which appears to be a truly novel, disjoint BRICHOS family. The C-terminal region of group C has nearly identical sequences in all species ranging from fish to man and is seemingly unique to this family, indicating critical functional or structural properties.
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| 6. |
- Lövborg, Henrik, et al.
(författare)
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Structure-activity relationship analysis of cytotoxic cyanoguanidines : selection of CHS 828 as candidate drug.
- 2009
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Ingår i: BMC research notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 2, s. 114-
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: N-(6-(4-chlorophenoxy)hexyl)-N'-cyano-N''-4-pyridyl guanidine) (CHS 828) is the first candidate drug from a novel group of anti-tumour agents - the pyridyl cyanoguanidines, shown to be potent compounds interfering with cellular metabolism (inhibition of nicotinamide phosphoribosyl transferase) and NF-kappaB signalling. Substituted cyanoguanidines are also found in anti-hypertensive agents such as the potassium channel opener pinacidil (N-cyano-N'-(4-pyridyl)-N''-(1,2,2-trimethylpropyl)guanidine) and histamine-II receptor antagonists (e.g. cimetidine, N-cyano-N'-methyl-N''-[2-[[(5-methylimidazol-4-yl]methyl]thio]ethyl)guanidine). In animal studies, CHS 828 has shown very promising activity, and phase I and II studies resulted in further development of a with a water soluble prodrug. FINDINGS: To study the structural requirements for cyanoguanidine cytotoxicity a set of 19 analogues were synthesized. The cytotoxic effects were then studied in ten cell lines selected for different origins and mechanisms of resistance, using the fluorometric microculture cytotoxicity assay (FMCA). The compounds showed varying cytotoxic activity even though the dose-response curves for some analogues were very shallow. Pinacidil and cimetidine were found to be non-toxic in all ten cell lines. Starting with cyanoguanidine as the crucial core it was shown that 4-pyridyl substitution was more efficient than was 3-pyridyl substitution. The 4-pyridyl cyanoguanidine moiety should be linked by an alkyl chain, optimally a hexyl, heptyl or octyl chain, to a bulky end group. The exact composition of this end group did not seem to be of crucial importance; when the end group was a mono-substituted phenyl ring it was shown that the preferred position was 4-substitution, followed by 3- and, finally, 2-substitution as the least active. Whether the substituent was a chloro, nitro or methoxy substituent seemed to be of minor importance. Finally, the activity patterns in the ten cell lines were compared. Substances with similar structures correlated well, whilst substances with large differences in molecular structure demonstrated lower correlation coefficients. CONCLUSION: According to this structure-activity relationship (SAR) study, CHS 828 meets the requirements for optimal cytotoxic activity for this class of compounds.
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| 7. |
- Chatterjee, Koushik, et al.
(författare)
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Fas and FasL gene polymorphisms are not associated with cervical cancer but differ among Black and Mixed-ancestry South Africans
- 2009
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Ingår i: BMC research notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 2, s. 238-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cervical cancer is one of the most important cancers in African women. Polymorphisms in the Fas (FasR) and Fas ligand (FasL) genes have been reported to be associated with cervical cancer in certain populations. This study investigated whether these polymorphisms are associated with cervical cancer or human papillomavirus (HPV) infection in South African women. FINDINGS: Participants were 447 women with invasive cervical cancer (106 black African and 341 women of mixed-ancestry) and 424 healthy women controls, matched by age, (101 black African and 323 women of mixed-ancestry) and domicile (rural or urban). Two polymorphisms in Fas gene (FasR-1377G/A, FasR-670A/G) and one in FasL gene (FasL844T/C) were genotyped by TaqMan. None of the polymorphisms, or the Fas haplotypes, showed a significant association with cervical cancer. There was also no association with HPV infection in the control group. However, on analysis of the control group, highly significant allele, genotype and haplotype differences were found between the two ethnic groups. There were generally low frequencies of FasR-1377A alleles, FasR-670A alleles and FasL-844C alleles in black women compared to the women of mixed-ancestry. CONCLUSION: This is the first study on the role of Fas and FasL polymorphisms in cervical cancer in African populations. Our results suggest that these SNPs are not associated with cervical cancer in these populations. The allele frequencies of the three SNPs differed markedly between the indigenous African black and mixed-ancestry populations.
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| 8. |
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