Subtle Recognition of 14-Base Pair DNA Sequences via Threading Polyintercalation

ABSTRACT: Small molecules that bind DNA in a sequence-specific manner could act as antibiotic, antiviral, or anticancer agents because of their potential ability to manipulate gene expression. Our laboratory has developed threading poly-intercalators based on 1,4,5,8-naphthalene diimide (NDI) units connected in a head-to-tail fashion by flexible peptide linkers. Previously, a threading tetraintercalator composed of alternating minor−major−minor groove-binding modules was shown to bind specifically to a 14 bp DNA sequence with a dissociation half-life of 16 days [Holman, G. G., et al. (2011) Nat. Chem. 3, 875−881]. Herein are described new NDI-based tetraintercalators with a different major groove-binding module and a reversed N to C directionality of one of the minor groove-binding modules. DNase I footprinting and kinetic analyses revealed that these new tetraintercalators are able to discriminate, by as much as 30-fold, 14 bp DNA binding sites that differ by 1 or 2 bp. Relative affinities were found to correlate strongly with dissociation rates, while overall C2 symmetry in the DNA-binding molecule appeared to contribute to enhanced association rates

Childhood maltreatment and psychotic experiences: exploring the specificity of early maladaptive schemas.

Objective: One potential mechanism that has received limited attention within psychosis research, is early maladaptive schemas (EMS). Our aim was to examine if EMS acts as a potential mediating pathway between early trauma and psychotic symptomology. Methods: A quantitative survey was hosted online. N=302 participants took part. The analysis employed a multiple mediation framework. Results: Analysis demonstrated significant specificity effects. Different forms of child maltreatment were significantly associated with psychosis experiences through specific dimensions of maladaptive schemas. Conclusions: Results indicated specificity effects in that specific types of maltreatment are associated with specific maladaptive schemas. From a practitioner’s perspective, these findings offer credence to cognitive theories of psychopathology, and support the validity of EMS identification and modification among clients with psychotic symptomology; both as a fundamental component of traditional CBT and within specialised schema focused therapy

Obstetricians and Violence against Women

I argue that the American Congress of Obstetricians and Gynecologists (ACOG), as an organization and through its individual members, can and should be a far greater ally in the prevention of violence against women. Specifically, I argue that we need to pay attention to obstetrical practices that inadvertently contribute to the problem of violence against women. While intimate partner violence is a complex phenomenon, I focus on the coercive control of women and adherence to oppressive gender norms. Using physician response to alcohol use during pregnancy and court-ordered medical treatment as examples, I show how some obstetrical practices mirror the attitudes of abusive men insofar as they try to coercively control women\u27s behavior through manipulation and violence. To be greater allies in the prevention of violence against women, obstetricians should stop participating in practices that inadvertently perpetuate violence against women

Effects of High-Fat Diet on eHSP72 and Extra-to-Intracellular HSP70 Levels in Mice Submitted to Exercise under Exposure to Fine Particulate Matter

Obesity, air pollution, and exercise induce alterations in the heat shock response (HSR), in both intracellular 70?kDa heat shock proteins (iHSP70) and the plasmatic extracellular form (eHSP72). Extra-to-intracellular HSP70 ratio (H-index?=?eHSP70/iHSP70 ratio) represents a candidate biomarker of subclinical health status. This study investigated the effects of moderate- and high-intensity exercise in the HSR and oxidative stress parameters, in obese mice exposed to fine particulate matter (PM2.5). Thirty-day-old male isogenic B6129F2/J mice were maintained for 16 weeks on standard chow or high-fat diet (HFD). Then, mice were exposed to either saline or 50?µg of PM2.5 by intranasal instillation and subsequently maintained at rest or subjected to moderate- or high-intensity swimming exercise. HFD mice exhibited high adiposity and glucose intolerance at week 16th. HFD mice submitted to moderate- or high-intensity exercise were not able to complete the exercise session and showed lower levels of eHSP70 and H-index, when compared to controls. PM2.5 exposure modified the glycaemic response to exercise and modified hematological responses in HFD mice. Our study suggests that obesity is a critical health condition for exercise prescription under PM2.5 exposure

Field test of single well DNAPL characterization using alcohol injection/extraction

Soils and groundwater beneath an abandoned process sewer line in the A/M Area of the Savannah River Site (SRS) contain elevated levels of volatile organic compounds, specifically trichloroethylene (TCE) and tetrachloroethylene (PCE), two common chlorinated solvents. These compounds have low aqueous solubilities, thus when released to the subsurface in sufficient quantity, tend to exist as immiscible fluids or nonaqueous phase liquids (NAPLs). Because chlorinated solvents are also denser than water, they are referred to by the acronym DNAPLs, or dense non-aqueous phase liquids. Technologies targeted at efficient characterization or removal of DNAPL are not currently proven. The authors performed injection/extraction characterization tests in six existing wells in A/M Area. Water concentrations for TCE and/or PCE in these wells ranged from 0% to 100% of solubility. For each test, small amounts of solubilizing solution were used to try to confirm or deny the presence or absence of DNAPL in the immediate vicinity of the well screen

VALUE OF PROSTATE SPECIFIC ANTIGEN IN PREDICTING THE EXISTENCE OF BONE METASTASIS IN SCINTIGRAPHY

ABSTRACT Objective: Evaluate the ability of serum concentration of prostate specific antigen (PSA) between 2 cutting points to predict the existence of bone metastasis confirmed by bone scintigraphy in man with prostate cancer. Materials and Methods: Two hundred and fourteen consecutive patients with prostate cancer were evaluated during the present study in the period from 1998 to 2001. From all patients, PSA serum concentrations and bone scintigraphy were obtained. For the study, 2 cutting points of PSA (10 and 20 ng/mL) were adopted to predict the existence of bone metastasis. Results: From the 214 patients, 35 (16.3%) presented positive scintigraphic examinations for the presence of bone metastasis. No patient presented bone metastasis in scintigraphy if having PSA < 10 ng/mL, and in only 1 patient (0.46%) with bone metastasis PSA concentration was < 20 ng/mL. Therefore, when the cutting point adopted for PSA serum concentration was 10 ng/mL, a negative predictive value for bone metastasis was 100% with sensitivity rates of 100%. Nevertheless, the positive predictive value and the specificity of the method were, respectively, 24.5% and 39.7%. When the cutting point of PSA serum concentration was 20 ng/mL, an increment was observed in rates of positive predictive value and specificity (41.5% and 73.2%), respectively, without substantial changes in negative predictive value (99.2%) and sensitivity (97.1%) of the method. Conclusions: Data of present study allow for the conclusion that PSA serum concentration over 20 ng/mL was a more accurate cutting point than PSA serum concentration over 10 ng/mL to predict the presence of bone metastasis in scintigraphy