241 research outputs found

    DNA Renaturation at the Water-Phenol Interface

    Get PDF
    We study DNA adsorption and renaturation in a water-phenol two-phase system, with or without shaking. In very dilute solutions, single-stranded DNA is adsorbed at the interface in a salt-dependent manner. At high salt concentrations the adsorption is irreversible. The adsorption of the single-stranded DNA is specific to phenol and relies on stacking and hydrogen bonding. We establish the interfacial nature of a DNA renaturation at a high salt concentration. In the absence of shaking, this reaction involves an efficient surface diffusion of the single-stranded DNA chains. In the presence of a vigorous shaking, the bimolecular rate of the reaction exceeds the Smoluchowski limit for a three-dimensional diffusion-controlled reaction. DNA renaturation in these conditions is known as the Phenol Emulsion Reassociation Technique or PERT. Our results establish the interfacial nature of PERT. A comparison of this interfacial reaction with other approaches shows that PERT is the most efficient technique and reveals similarities between PERT and the renaturation performed by single-stranded nucleic acid binding proteins. Our results lead to a better understanding of the partitioning of nucleic acids in two-phase systems, and should help design improved extraction procedures for damaged nucleic acids. We present arguments in favor of a role of phenol and water-phenol interface in prebiotic chemistry. The most efficient renaturation reactions (in the presence of condensing agents or with PERT) occur in heterogeneous systems. This reveals the limitations of homogeneous approaches to the biochemistry of nucleic acids. We propose a heterogeneous approach to overcome the limitations of the homogeneous viewpoint

    Lead-free piezoceramics - Where to move on?

    Get PDF
    Lead-free piezoceramics aiming at replacing the market-dominant lead-based ones have been extensively searched for more than a decade worldwide. Some noteworthy outcomes such as the advent of commercial products for certain applications have been reported, but the goal, i.e., the invention of a lead-free piezocermic, the performance of which is equivalent or even superior to that of PZT-based piezoceramics, does not seem to be fulfilled yet. Nevertheless, the academic effort already seems to be culminated, waiting for a guideline to a future research direction. We believe that a driving force for a restoration of this research field needs to be found elsewhere, for example, intimate collaborations with related industries. For this to be effectively realized, it would be helpful for academic side to understand the interests and demands of the industry side as well as to provide the industry with new scientific insights that would eventually lead to new applications. Therefore, this review covers some of the issues that are to be studied further and deeper, so-to-speak, lessons from the history of piezoceramics, and some technical issues that could be useful in better understanding the industry demands. As well, the efforts made in the industry side will be briefly introduced for the academic people to catch up with the recent trends and to be guided for setting up their future research direction effectively.ope

    Seasonal variations in pore water and sediment geochemistry of littoral lake sediments (Asylum Lake, MI, USA)

    Get PDF
    BACKGROUND: Seasonal changes in pore water and sediment redox geochemistry have been observed in many near-surface sediments. Such changes have the potential to strongly influence trace metal distribution and thus create seasonal fluctuations in metal mobility and bioavailability. RESULTS: Seasonal trends in pore water and sediment geochemistry are assessed in the upper 50 cm of littoral kettle lake sediments. Pore waters are always redox stratified, with the least compressed redox stratification observed during fall and the most compressed redox stratification observed during summer. A 2-step sequential sediment extraction yields much more Fe in the first step, targeted at amorphous Fe(III) (hydr)oxides (AEF), then in the second step, which targets Fe(II) monosulfides. Fe extracted in the second step is relatively invariant with depth or season. In contrast, AEF decreases with sediment depth, and is seasonally variable, in agreement with changes in redox stratification inferred from pore water profiles. A 5-step Tessier extraction scheme was used to assess metal association with operationally-defined exchangeable, carbonate, iron and manganese oxide (FMO), organic/sulfide and microwave-digestible residual fractions in cores collected during winter and spring. Distribution of metals in these two seasons is similar. Co, As, Cd, and U concentrations approach detection limits. Fe, Cu and Pb are mostly associated with the organics/sulfides fraction. Cr and Zn are mostly associated with FMO. Mn is primarily associated with carbonates, and Co is nearly equally distributed between the FMO and organics/sulfide fractions. CONCLUSION: This study clearly demonstrates that near-surface lake sediment pore water redox stratification and associated solid phase geochemistry vary significantly with season. This has important ramifications for seasonal changes in the bioavailability and mobility of trace elements. Without rate measurements, it is not possible to quantify the contribution of various processes to natural organic matter degradation. However, the pore water and solid phase data suggest that iron reduction and sulfate reduction are the dominant pathways in the upper 50 cm of these sediments

    Functional Impairment of Central Memory CD4 T Cells Is a Potential Early Prognostic Marker for Changing Viral Load in SHIV-Infected Rhesus Macaques

    Get PDF
    In HIV infection there is a paucity of literature about the degree of immune dysfunction to potentially correlate and/or predict disease progression relative to CD4+ T cells count or viral load. We assessed functional characteristics of memory T cells subsets as potential prognostic markers for changing viral loads and/or disease progression using the SHIV-infected rhesus macaque model. Relative to long-term non-progressors with low/undetectable viral loads, those with chronic plasma viremia, but clinically healthy, exhibited significantly lower numbers and functional impairment of CD4+ T cells, but not CD8+ T cells, in terms of IL-2 production by central memory subset in response to PMA and ionomycine (PMA+I) stimulation. Highly viremic animals showed impaired cytokine-production by all T cells subsets. These results suggest that functional impairment of CD4+ T cells in general, and of central memory subset in particular, may be a potential indicator/predictor of chronic infection with immune dysfunction, which could be assayed relatively easily using non-specific PMA+I stimulation

    Inflammatory arthritis in HIV positive patients: A practical guide

    Get PDF
    Background: Musculoskeletal manifestations of the human immunodeficiency virus (HIV) have been described since the outset of the global HIV epidemic. Articular syndromes that have been described in association with HIV include HIV-associated arthropathy, seronegative spondyloarthropathies (SPA) (reactive arthritis, psoriatic arthritis (PsA) and undifferentiated SPA), rheumatoid arthritis (RA) and painful articular syndrome. Methods: We carried out a computer-assisted search of PubMed for the medical literature from January 1981 to January 2015 using the keywords HIV, acquired immune-deficiency syndrome, rheumatic manifestations, arthritis, spondyloarthropathy, anti-TNF and disease modifying antirheumatic drugs. Only English language literature was included and only studies involving adult human subjects were assessed. Results: There are challenges in the management of inflammatory arthritis in patients who are HIV-positive, including difficulties in the assessment of disease activity and limited information on the safety of immunosuppressive drugs in these individuals. Conclusions: This review focuses on the clinical characteristics of the inflammatory articular syndromes that have been described in association with HIV infection and discusses the therapeutic options for these patients

    PR1-Specific T Cells Are Associated with Unmaintained Cytogenetic Remission of Chronic Myelogenous Leukemia After Interferon Withdrawal

    Get PDF
    Interferon-alpha (IFN) induces complete cytogenetic remission (CCR) in 20-25% CML patients and in a small minority of patients; CCR persists after IFN is stopped. IFN induces CCR in part by increasing cytotoxic T lymphocytes (CTL) specific for PR1, the HLA-A2-restricted 9-mer peptide from proteinase 3 and neutrophil elastase, but it is unknown how CCR persists after IFN is stopped.We reasoned that PR1-CTL persist and mediate CML-specific immunity in patients that maintain CCR after IFN withdrawal. We found that PR1-CTL were increased in peripheral blood of 7/7 HLA-A2+ patients during unmaintained CCR from 3 to 88 months after IFN withdrawal, as compared to no detectable PR1-CTL in 2/2 IFN-treated CML patients not in CCR. Unprimed PR1-CTL secreted IFNgamma and were predominantly CD45RA+/-CD28+CCR7+CD57-, consistent with functional naïve and central memory (CM) T cells. Similarly, following stimulation, proliferation occurred predominantly in CM PR1-CTL, consistent with long-term immunity sustained by self-renewing CM T cells. PR1-CTL were functionally anergic in one patient 6 months prior to cytogenetic relapse at 26 months after IFN withdrawal, and in three relapsed patients PR1-CTL were undetectable but re-emerged 3-6 months after starting imatinib.These data support the hypothesis that IFN elicits CML-specific CM CTL that may contribute to continuous CCR after IFN withdrawal and suggest a role for T cell immune therapy with or without tyrosine kinase inhibitors as a strategy to prolong CR in CML

    The bisphosphonate pamidronate induces apoptosis in human melanoma cells in vitro

    Get PDF
    Pamidronate belongs to the class of nitrogen-containing bisphosphonates that are potent inhibitors of bone resorption frequently used for the treatment of osteoporosis and cancer-induced osteolysis. The inhibition of osteoclasts’ growth has been suggested as the main mechanism of the inhibitory effect of pamidronate on bone metastases. Recent findings indicated that bisphosphonates also have a direct apoptotic effect on other types of tumour cells. Nitrogen-containing bisphosphonates were shown to inhibit farnesyl diphosphate synthase, thus blocking the synthesis of higher isoprenoids. By this mechanism they inactivate monomeric G-proteins of the Ras and Rho families for which prenylation is a functional requirement. On the background of the known key role of G-proteins in tumorigenesis, we investigated a possible beneficial use of pamidronate in the treatment of malignant melanoma. Our results indicate that pamidronate inhibits the cell growth and induces apoptosis in human melanoma cells in vitro. Susceptibility to pamidronate did not correlate to CD95 ligand sensitivity or p53 mutational status. Furthermore it is interesting to note that overexpression of bcl-2 did not abolish pamidronate-induced apoptosis. These data suggests that pamidronate has a direct anti-tumour effect on malignant melanoma cells, independently of the Bax/Bcl-2 level
    corecore