961 research outputs found

    Structural characterization and physical properties of P2O5-CaO-Na2O-TiO2 glasses by Fourier transform infrared, Raman and solid-state magic angle spinning nuclear magnetic resonance spectroscopies.

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    Phosphate-based glasses have been investigated for tissue engineering applications. This study details the properties and structural characterization of titanium ultra-phosphate glasses in the 55(P(2)O(5))-30(CaO)-(25-x)(Na(2)O)-x(TiO(2)) (0≤x≤5) system, which have been prepared via melt-quenching techniques. Structural characterization was achieved by a combination of X-ray diffraction (XRD), and solid-state nuclear magnetic resonance, Raman and Fourier transform infrared spectroscopies. Physical properties were also investigated using density, degradation and ion release studies; additionally, differential thermal analysis was used for thermal analysis of these glasses. The results show that with the addition of TiO(2) the density and glass transition temperature increased whereas the degradation and ion release properties are decreased. From XRD data, TiP(2)O(7) and CaP(2)O(6) were detected in 3 and 5 mol.% TiO(2)-containing glasses. Magic angle spinning nuclear magnetic resonance results confirmed that as TiO(2) is incorporated into the glass; the amount of Q(3) increases as the amount of Q(2) consequently decreases, indicating increasing polymerization of the phosphate network. Spectroscopy results also showed that the local structure of glasses changes with increasing TiO(2) content. As TiO(2) is incorporated into the glass, the phosphate connectivity increases, indicating that the addition of TiO(2) content correlates unequivocally with an increase in glass stability

    Using the Traditional Ex Vivo Whole Blood Model to Discriminate Bacteria by Their Inducible Host Responses

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    \ua9 2024 by the authors.Whole blood models are rapid and versatile for determining immune responses to inflammatory and infectious stimuli, but they have not been used for bacterial discrimination. Staphylococcus aureus, S. epidermidis and Escherichia coli are the most common causes of invasive disease, and rapid testing strategies utilising host responses remain elusive. Currently, immune responses can only discriminate between bacterial ‘domains’ (fungi, bacteria and viruses), and very few studies can use immune responses to discriminate bacteria at the species and strain level. Here, whole blood was used to investigate the relationship between host responses and bacterial strains. Results confirmed unique temporal profiles for the 10 parameters studied: IL-6, MIP-1α, MIP-3α, IL-10, resistin, phagocytosis, S100A8, S100A8/A9, C5a and TF3. Pairwise analysis confirmed that IL-6, resistin, phagocytosis, C5a and S100A8/A9 could be used in a discrimination scheme to identify to the strain level. Linear discriminant analysis (LDA) confirmed that (i) IL-6, MIP-3α and TF3 could predict genera with 95% accuracy; (ii) IL-6, phagocytosis, resistin and TF3 could predict species at 90% accuracy and (iii) phagocytosis, S100A8 and IL-10 predicted strain at 40% accuracy. These data are important because they confirm the proof of concept that host biomarker panels could be used to identify bacterial pathogens

    Ocean acidification impacts on nitrogen fixation in the coastal western Mediterranean Sea

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    The effects of ocean acidification on nitrogen (N2) fixation rates and on the community composition of N2-fixing microbes (diazotrophs) were examined in coastal waters of the North-Western Mediterranean Sea. Nine experimental mesocosm enclosures of ∼50 m3 each were deployed for 20 days during June-July 2012 in the Bay of Calvi, Corsica, France. Three control mesocosms were maintained under ambient conditions of carbonate chemistry. The remainder were manipulated with CO2 saturated seawater to attain target amendments of pCO2 of 550, 650, 750, 850, 1000 and 1250 μatm. Rates of N2 fixation were elevated up to 10 times relative to control rates (2.00 ± 1.21 nmol L-1d-1) when pCO2 concentrations were >1000 μatm and pHT (total scale) < 7.74. Diazotrophic phylotypes commonly found in oligotrophic marine waters, including the Mediterranean, were not present at the onset of the experiment and therefore, the diazotroph community composition was characterised by amplifying partial nifH genes from the mesocosms. The diazotroph community was comprised primarily of cluster III nifH sequences (which include possible anaerobes), and proteobacterial (α and γ) sequences, in addition to small numbers of filamentous (or pseudo-filamentous) cyanobacterial phylotypes. The implication from this study is that there is some potential for elevated N2 fixation rates in the coastal western Mediterranean before the end of this century as a result of increasing ocean acidification. Observations made of variability in the diazotroph community composition could not be correlated with changes in carbon chemistry, which highlights the complexity of the relationship between ocean acidification and these keystone organisms

    Evolutionary factors affecting Lactate dehydrogenase A and B variation in the Daphnia pulex species complex

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    Background: Evidence for historical, demographic and selective factors affecting enzyme evolution can be obtained by examining nucleotide sequence variation in candidate genes such as Lactate dehydrogenase (Ldh). Two closely related Daphnia species can be distinguished by their electrophoretic Ldh genotype and habitat. Daphnia pulex populations are fixed for the S allele and inhabit temporary ponds, while D. pulicaria populations are fixed for the F allele and inhabit large stratified lakes. One locus is detected in most allozyme surveys, but genome sequencing has revealed two genes, LdhA and LdhB. Results: We sequenced both Ldh genes from 70 isolates of these two species from North America to determine if the association between Ldh genotype and habitat shows evidence for selection, and to elucidate the evolutionary history of the two genes. We found that alleles in the pond-dwelling D. pulex and in the lake-dwelling D. pulicaria form distinct groups at both loci, and the substitution of Glutamine (S) for Glutamic acid (F) at amino acid 229 likely causes the electrophoretic mobility shift in the LDHA protein. Nucleotide diversity in both Ldh genes is much lower in D. pulicaria than in D. pulex. Moreover, the lack of spatial structuring of the variation in both genes over a wide geographic area is consistent with a recent demographic expansion of lake populations. Neutrality tests indicate that both genes are under purifying selection, but the intensity is much stronger on LdhA. Conclusions: Although lake-dwelling D. pulicaria hybridizes with the other lineages in the pulex species complex, it remains distinct ecologically and genetically. This ecological divergence, coupled with the intensity of purifying selection on LdhA and the strong association between its genotype and habitat, suggests that experimental studies would be useful to determine if variation in molecular function provides evidence that LDHA variants are adaptive

    Association of specific chromosome alterations with tumour phenotype in posterior uveal melanoma

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    Posterior uveal melanomas have recurrent alterations of chromosomes 1, 3, 6 and 8. In particular, changes of chromosomes 3 and 8 occur in association, appear to characterize those tumours with a ciliary body component, and have been shown to be of prognostic significance. The relevance of other chromosome alterations is less certain. We have performed cytogenetic analysis on 42 previously untreated primary posterior uveal melanomas. Of interest was the observation that as tumour size increased the involvement of specific chromosome changes, and the amount of chromosome abnormalities likewise increased. Loss, or partial deletions, of the short arm of chromosome 1 were found to associate with larger ciliary body melanomas; typically, loss of the short arm resulted from unbalanced translocations, the partners of which varied. Trisomy of chromosome 21 occurred more often in ciliary body melanomas, whilst rearrangements of chromosomes 6 and 11 were primarily related to choroidal melanomas. Our results imply that alterations of chromosome 1 are important in the progression of some uveal melanomas, and that other chromosome abnormalities, besides those of chromosomes 3 and 8, are associated with ocular tumours of particular locations. © 2000 Cancer Research Campaig

    HAGE (DDX43) is a biomarker for poor prognosis and a predictor of chemotherapy response in breast cancer

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    Background: HAGE protein is a known immunogenic cancer-specific antigen. Methods: The biological, prognostic and predictive values of HAGE expression was studied using immunohistochemistry in three cohorts of patients with BC (n=2147): early primary (EP-BC; n=1676); primary oestrogen receptor-negative (PER-BC; n=275) treated with adjuvant anthracycline-combination therapies (Adjuvant-ACT); and primary locally advanced disease (PLA-BC) who received neo-adjuvant anthracycline-combination therapies (Neo-adjuvant-ACT; n=196). The relationship between HAGE expression and the tumour-infiltrating lymphocytes (TILs) in matched prechemotherapy and postchemotherapy samples were investigated. Results: Eight percent of patients with EP-BC exhibited high HAGE expression (HAGEþ) and was associated with aggressive clinico-pathological features (Ps<0.01). Furthermore, HAGEþexpression was associated with poor prognosis in both univariate and multivariate analysis (Ps<0.001). Patients with HAGE+ did not benefit from hormonal therapy in high-risk ER-positive disease. HAGE+ and TILs were found to be independent predictors for pathological complete response to neoadjuvant-ACT; P<0.001. A statistically significant loss of HAGE expression following neoadjuvant-ACT was found (P=0.000001), and progression-free survival was worse in those patients who had HAGE+ residual disease (P=0.0003). Conclusions: This is the first report to show HAGE to be a potential prognostic marker and a predictor of response to ACT in patients with BC

    Schizophrenia copy number variants and associative learning

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    Large-scale genomic studies have made major progress in identifying genetic risk variants for schizophrenia. A key finding from these studies is that there is an increased burden of genomic copy number variants (CNVs) in schizophrenia cases compared with controls. The mechanism through which these CNVs confer risk for the symptoms of schizophrenia, however, remains unclear. One possibility is that schizophrenia risk CNVs impact basic associative learning processes, abnormalities of which have long been associated with the disorder. To investigate whether genes in schizophrenia CNVs impact on specific phases of associative learning we combined human genetics with experimental gene expression studies in animals. In a sample of 11 917 schizophrenia cases and 16 416 controls, we investigated whether CNVs from patients with schizophrenia are enriched for genes expressed during the consolidation, retrieval or extinction of associative memories. We show that CNVs from cases are enriched for genes expressed during fear extinction in the hippocampus, but not genes expressed following consolidation or retrieval. These results suggest that CNVs act to impair inhibitory learning in schizophrenia, potentially contributing to the development of core symptoms of the disorder

    Hampered Foraging and Migratory Performance in Swans Infected with Low-Pathogenic Avian Influenza A Virus

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    It is increasingly acknowledged that migratory birds, notably waterfowl, play a critical role in the maintenance and spread of influenza A viruses. In order to elucidate the epidemiology of influenza A viruses in their natural hosts, a better understanding of the pathological effects in these hosts is required. Here we report on the feeding and migratory performance of wild migratory Bewick's swans (Cygnus columbianus bewickii Yarrell) naturally infected with low-pathogenic avian influenza (LPAI) A viruses of subtypes H6N2 and H6N8. Using information on geolocation data collected from Global Positioning Systems fitted to neck-collars, we show that infected swans experienced delayed migration, leaving their wintering site more than a month after uninfected animals. This was correlated with infected birds travelling shorter distances and fuelling and feeding at reduced rates. The data suggest that LPAI virus infections in wild migratory birds may have higher clinical and ecological impacts than previously recognised
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