The fifth base: A natural feature of dinoflagellate DNA

The presence of 5-Hydroxymethyluracil which replaces important fractions of thymine in Dinoflagellate DNA is analyzed according to different procaryotic models of biosynthesis. The detection of HOMeU inAmphidinum carterae cells suggests an incorporation of this 5th base during polymerisation of DNA chains rather than a post-synthetic modification of thymines. A relationship between HOMeU and the permanent repair-like DNA synthesis observed inA. carterae is discussed.     

Anticonvulsant use and fracture: a case-control study

Objectives:We aimed to investigate fracture risk associated with anticonvulsant use in a population-based sample of men and women.Methods:Data from 1,458 participants (51.8% women) with a radiologically confirmed incident fracture (cases) were compared to 1,796 participants (46.5% women) without fracture (controls). Lifestyle factors, medication use and medical history were self-reported. Associations between anticonvulsant use and fracture were explored using binary logistic regression following adjustment for confounders.Results:In men, fracture cases and controls differed in age, smoking history, education, alcohol use, and gonadal hormone supplementation. In women, fracture cases and controls differed by previous fracture history, alcohol use, physical activity levels and use of anti-fracture agents. After adjustment for age, pooled anticonvulsant use was associated with a 3.4-fold higher risk of fracture in men and a 1.8-fold higher risk in women. Following further adjustments for confounders these patterns persisted; a 2.8-fold higher fracture risk in men and a 1.8-fold higher fracture risk in women.Conclusions:Anticonvulsant use was associated with increased fracture risk, independent of demographic, lifestyle, medical and medication related factors. While further studies exploring potential underlying mechanisms are warranted, regular monitoring of bone health in anticonvulsant users with risk factors may be useful.     

Lewis base interaction with gallium hydrides: a computational study

The recent synthesis and structural characterization of the complex of 3,5-dimethyl-4-hydropyridyl-gallane 1 with the Lewis base 3,5-dimethylpyridine revealed an unusually large angle α = H-Ga-H, 127(2)°, at variance with expected steric effects of the bulky substituents at the tetrahedrally coordinated Ga center. This finding prompted us to study computationally gallium hydrides using density functional and post-Hartree-Fock methods. For 1, we estimated α at 131° from a calculation on 4-hydropyridyl-gallane, GaH₂(Hpy). This value is reduced by 3° due to the interaction with Lewis base pyridine, to yield α = 128°, in excellent agreement with experiment. With an analysis of orbital interactions and a natural bond orbital analysis, we rationalized structural variations of donor-acceptor adducts LGaH₂X where X is a substituent and L is a Lewis base. Angle α is mainly determined by the polarity of the Ga-X bond: the more electronegative substituent X, the larger α and the stronger the interaction of GaH₂X with L. Interaction with a weak base L slightly distorts the initially planar geometry of the dihydride to a trigonal pyramidal form; for a strong base, the structure can become pseudo-tetrahedral.     

The influence of base identity and base pairing on the function of the alpha-sarcin loop of 23S rRNA.

The alpha-sarcin loop of large subunit rRNAs is one of the sites of interaction of elongation factors with the ribosome, and the target of the cytotoxins alpha-sarcin and ricin. Using a genetic selection for increased frameshifting in a reporter gene, we have isolated a C --> U mutation at position 2666 in the alpha-sarcin loop. In the NMR-derived structure of the loop, bases equivalent to 2666 and 2654 are paired via a non-canonical base pairing interaction. Each of the three base substitutions at C2666 and A2654 was constructed by site-directed mutagenesis of a plasmid borne copy of the rrnB operon of Escherichia coli. Only the C2666 --> U and A2654 --> G mutations that resulted in the formation of canonical A-U and C-G base pairs respectively, increased the levels of stop codon readthrough and frameshifting. The effects of different base pair combinations at positions 2666 and 2654 on ribosome function were then tested by constructing and analyzing all possible base combinations at these sites. All A --> G base substitution mutations at position 2654 and C --> U substitutions at position 2666 increased the levels of translational errors. However, these effects were greatest when G2654 and U2666 had the potential to engage in standard Watson-Crick base pairing interactions. These data indicate that base identity as well as base pairing interactions are important for the function of this essential component of the large subunit rRNA.     

23Na NMR relaxation study of the effects of conformation and base composition on the interactions of counterions with double-helical DNA

NMR relaxation rates (T1(-1) and T2(-1)) have been determined for 23Na in aqueous salt solutions containing various types of helical double-stranded deoxyribonucleic acids. These measurements were performed on three synthetic polynucleotides having different overall conformations, poly-(dA-dT).poly(dA-dT) (alternating B-DNA), poly(dG-dC).poly(dG-dC) at low salt (B-DNA), and Br-poly(dG-dC).Br-poly(dG-dC) (left-handed Z-DNA), and on four types of natural DNA differing in base composition, Clostridium perfringens (26% GC), calf thymus (40% GC), Escherichia coli (50% GC), and Micrococcus lysodeikticus (72% GC). For all types of DNA investigated, except poly(dA-dT).poly(dA-dT), the 23Na NMR spectra measured at 21 degrees C and an applied field of 4.7 T are non-Lorentzian. These non-Lorentzian spectra were analyzed on the basis of the two-state model and the standard theory of nonexponential quadrupolar relaxation processes in order to obtain estimates of the correlation times (tau c) characteristic of the sodium nuclei associated with the various nucleic acids. All of the correlation times estimated in this way are in the range of nanoseconds. The magnitudes of these correlation times show a significant dependence on the overall conformation of the nucleic acid (B vs. Z) but not on its base composition. To investigate the concentration dependence of tau c, sodium or magnesium salts were added to solutions of Br-poly(dG-dC).Br-poly(dG-dC) (Z-DNA).(ABSTRACT TRUNCATED AT 250 WORDS)     

Reduced trabecular bone mineral density and cortical thickness accompanied by increased outer bone circumference in metacarpal bone of rheumatoid arthritis patients: a cross-sectional study

Introduction

The objective of this study was to assess three-dimensional bone geometry and density at the epiphysis and shaft of the third meta-carpal bone of rheumatoid arthritis (RA) patients in comparison to healthy controls with the novel method of peripheral quantitative computed tomography (pQCT).

Methods

PQCT scans were performed in 50 female RA patients and 100 healthy female controls at the distal epiphyses and shafts of the third metacarpal bone, the radius and the tibia. Reproducibility was determined by coefficient of varia-tion. Bone densitometric and geometric parameters were compared between the two groups and correlated to disease characteristics.

Results

Reproducibility of different pQCT parameters was between 0.7% and 2.5%. RA patients had 12% to 19% lower trabecular bone mineral density (BMD) (P ≤ 0.001) at the distal epiphyses of radius, tibia and metacarpal bone. At the shafts of these bones RA patients had 7% to 16% thinner cortices (P ≤ 0.03). Total cross-sectional area (CSA) at the metacarpal bone shaft of pa-tients was larger (between 5% and 7%, P < 0.02), and relative cortical area was reduced by 13%. Erosiveness by Ratingen score correlated negatively with tra-becular and total BMD at the epiphyses and shaft cortical thickness of all measured bones (P < 0.04).

Conclusions

Reduced trabecular BMD and thinner cortices at peripheral bones, and a greater bone shaft diameter at the metacarpal bone suggest RA spe-cific bone alterations. The proposed pQCT protocol is reliable and allows measuring juxta-articular trabecular BMD and shaft geometry at the metacarpal bone.     

Symbiotic complexity: discovery of a fifth symbiont in the attine ant-microbe symbiosis

The fungus-growing ant-microbe mutualism is a classic example of organismal complexity generated through symbiotic association. The ants have an ancient obligate mutualism with fungi they cultivate for food. The success of the mutualism is threatened by specialized fungal parasites (Escovopsis) that consume the cultivated fungus. To defend their nutrient-rich garden against infection, the ants have a second mutualism with bacteria (Pseudonocardia), which produce antibiotics that inhibit the garden parasite Escovopsis. Here we reveal the presence of a fourth microbial symbiont associated with fungus-growing ants: black yeasts (Ascomycota; Phialophora). We show that black yeasts are commonly associated with fungus-growing ants, occurring throughout their geographical distribution. Black yeasts grow on the ants' cuticle, specifically localized to where the mutualistic bacteria are cultured. Molecular phylogenetic analyses reveal that the black yeasts form a derived monophyletic lineage associated with the phylogenetic diversity of fungus growers. The prevalence, distribution, localization and monophyly indicate that the black yeast is a fifth symbiont within the attine ant-microbe association, further exemplifying the complexity of symbiotic associations.     

The mechanism of TC23O's thermostability: a molecular dynamics simulation study

The quasielastic neutron scattering index beta and the modulus of a protein's quasi-electric dipole moment were utilized to quantitate the thermostability of wildtype TC23O and its mutants. Charged residues Arg314, Glu246, Glu291, and some prolines near the C-terminus of the sequence (Pro228, Pro296, and Pro308) were identified to be critical for the thermostability of wildtype TC23O according to these two criteria. By analyzing the molecular conformation changes during the simulation, it was demonstrated how the mutant P228S was destabilized by disrupting two salt-bridges Asp116OD1-Lys215N and Glu210OE1-Lys217N at an adjacent beta-turn. The destabilization of P296S also shown to be intimate correlated with the break down of ion pair Lys188N-Glu291OE1. The sensitivity of its electrostatic network to the local structure is an important feature. It reveals that the 'proline effect' and electrostatic interactions together influences the thermostability of TC23O a lot.     

The interaction of polyamines with DNA: a 23Na NMR study.

The interaction between a variety of polyamines, both naturally occurring and synthetic, and calf thymus DNA has been studied using 23Na NMR. The relaxation behaviour of 23Na reflects the extent of interaction of Na+ with DNA phosphate groups and therefore the extent of charge neutralisation of DNA phosphate groups (P) by polyamine amino and imino groups (N) in solutions of DNa, polyamine and Na+. The studies reveal that whereas spermine and spermidine are capable of expelling nearly all of the Na+ ions from DNA at N/P approximately 1, diamines such as putrescine and homologues of spermine and spermidine are capable of neutralising only roughly 50% of DNA phosphates. The results provide a challenge to current models of DNA-polyamine interactions.     

侵袭性肺曲霉病临床和病理分析——附23例报告

目的 分析侵袭性肺曲霉病(IPA)临床和组织病理特征,为探讨IPA早期诊断和临床病理分型提供依据.方法 非选择性地总结本院34年来512例成人(年龄≥16岁)尸检资料,依据病理切片真菌形态确定IPA患者共23例,并进行临床和病理对照分析.结果 23例中有明确基础疾病者21例,有明确诱因者20例.临床上表现有发热等中毒症状者17例(73.91%),合并呼吸道症状者18例(78.26%),存在肺部和肺外栓塞征象者9例(3.91%).胸部影像表现和病理检查符合急性支气管肺炎型15例次,血管侵袭型12例次,急性气管支气管炎型5例次,粟粒型3例次和胸膜炎型1例次.其中急性支气管炎型和血管侵袭型常合并存在,并成为患者致死的直接原因.结论 IPA临床表现复杂多变,探讨临床尤其是胸部影像学检查和组织病理分型有利于患者的早期诊断和判断预后.     

Methodological reflections on using pilot data from fracture patients to develop a qualitative study

Background

Qualitative studies are particularly valued for their exploratory nature but, like other research methods, they do require careful planning to ensure rigorous study design. Our objective was to undertake a pilot study to inform the development of a larger qualitative study.

Results

We conducted a series of brief interviews with out-patients in a hospital setting. The interviews were designed to elicit superficial information about whether (and how) post-fracture osteoporosis investigation and/or treatment were being initiated among patients receiving treatment or follow-up for a current or recent fracture. We used thematic analysis to identify key themes in the data that related to the broader research questions.We analysed data obtained from 11 out of a total of 12 interviews conducted. Participants were male and female, aged 19-83 years of age (median age 57 years). Participants attended 2-8 medical appointments to seek treatment and follow up for a current or recent fracture. The following four overarching themes emerged from thematic analysis of the data: fracture event, referral pathway, osteoporosis investigation and/or treatment, and communication by health practitioners and staff.

Conclusions

This pilot study was necessarily tentative and exploratory in nature, but provided a helpful snapshot of some typical experiences in the public health system following fracture. Several themes emerged for consideration in the design of the main study.Despite its critics, theoretical sampling and saturation continue to provide sustainable methods for ensuring that relevant themes and categories are covered in sufficient depth and breadth, appropriate to the needs of the study.

     

Infarction in the territory of the anterior cerebral artery: clinical study of 51 patients

Background

Little is known about clinical features and prognosis of patients with ischaemic stroke caused by infarction in the territory of the anterior cerebral artery (ACA). This single centre, retrospective study was conducted with the following objectives: a) to describe the clinical characteristics and short-term outcome of stroke patients with ACA infarction as compared with that of patients with ischaemic stroke due to middle cerebral artery (MCA) and posterior cerebral artery (PCA) infarctions, and b) to identify predictors of ACA stroke.

Methods

Fifty-one patients with ACA stroke were included in the "Sagrat Cor Hospital of Barcelona Stroke Registry" during a period of 19 years (1986–2004). Data from stroke patients are entered in the stroke registry following a standardized protocol with 161 items regarding demographics, risk factors, clinical features, laboratory and neuroimaging data, complications and outcome. The characteristics of these 51 patients with ACA stroke were compared with those of the 1355 patients with MCA infarctions and 232 patients with PCA infarctions included in the registry.

Results

Infarctions of the ACA accounted for 1.3% of all cases of stroke (n = 3808) and 1.8% of cerebral infarctions (n = 2704). Stroke subtypes included cardioembolic infarction in 45.1% of patients, atherothrombotic infarction in 29.4%, lacunar infarct in 11.8%, infarct of unknown cause in 11.8% and infarction of unusual aetiology in 2%. In-hospital mortality was 7.8% (n = 4). Only 5 (9.8%) patients were symptom-free at hospital discharge. Speech disturbances (odds ratio [OR] = 0.48) and altered consciousness (OR = 0.31) were independent variables of ACA stroke in comparison with MCA infarction, whereas limb weakness (OR = 9.11), cardioembolism as stroke mechanism (OR = 2.49) and sensory deficit (OR = 0.35) were independent variables associated with ACA stroke in comparison with PCA infarction.

Conclusion

Cardioembolism is the main cause of brain infarction in the territory of the ACA. Several clinical features are more frequent in stroke patients with ACA infarction than in patients with ischaemic stroke due to infarction in the MCA and PCA territories.