Twin hydroxymethyluracil-A base pair steps define the binding site for the DNA-bending protein TF1

The DNA-bending protein TF1 is the Bacillus subtilis bacteriophage SPO1- encoded homolog of the bacterial HU proteins and the Escherichia coli integration host factor. We recently proposed that TF1, which binds with high affinity (K(d) was ~3 nM) to preferred sites within the hydroxymethyluracil (hmU)-containing phage genome, identifies its binding sites based on sequence-dependent DNA flexibility. Here, we show that two hmU-A base pair steps coinciding with two previously proposed sites of DNA distortion are critical for complex formation. The affinity of TF1 is reduced 10-fold when both of these hmU-A base pair steps are replaced with A-hmU, G-C, or C-G steps; only modest changes in affinity result when substitutions are made at other base pairs of the TF1 binding site. Replacement of all hmU residues with thymine decreases the affinity of TF1 greatly; remarkably, the high affinity is restored when the two hmU-A base pair steps corresponding to previously suggested sites of distortion are reintroduced into otherwise T- containing DNA. T-DNA constructs with 3-base bulges spaced apart by 9 base pairs of duplex also generate nM affinity of TF1. We suggest that twin hmU-A base pair steps located at the proposed sites of distortion are key to target site selection by TF1 and that recognition is based largely, if not entirely, on sequence-dependent DNA flexibility

Investigating the properties of TBA variants with twin thrombin binding domains

In this paper, we report studies concerning thrombin binding aptamer (TBA) dimeric derivatives in which the 3'-ends of two TBA sequences have been joined by means of linkers containing adenosine or thymidine residues and/or a glycerol moiety. CD and electrophoretic investigations indicate that all modified aptamers are able to form G-quadruplex domains resembling that of the parent TBA structure. However, isothermal titration calorimetry measurements of the aptamer/thrombin interaction point to different affinities to the target protein, depending on the type of linker. Consistently, the best ligands for thrombin show anticoagulant activities higher than TBA. Interestingly, two dimeric aptamers with the most promising properties also show far higher resistances in biological environment than TBA

Smoking habits among Italian adolescents: what has changed in the last decade?

Tobacco use, alcohol abuse, overweight and obesity are risk factors for numerous diseases in Italy as elsewhere. However, children and adolescents are not usually included in official national surveys although it is at this stage of life when unhealthy habits are often established. Italian participation in HBSC and GYTS surveys allows our country to implement standardized surveillance systems providing reliable information on tobacco-related behaviors of this population. Data from three HBSC surveys (2002–2010) show that following the drop in the first half of the decade, prevalence of tobacco use stabilized in the second half. The decline was significant for younger age groups, while prevalence of regular tobacco use remained stable among 15-year-olds. Many adolescents reported being exposed to secondhand smoke, to have at least one parent who smokes, and having seen teachers and students smoking at school. Although the sale of tobacco products to minors is prohibited, the vast majority had no trouble in buying cigarettes. Data from GYTS and HBSC surveys provide a wealth of information about attitudes and behaviors of Italian adolescents with respect to smoking. Despite some progress, sizeable gaps remain in meeting standard recommendations for discouraging smoking initiation and motivating adolescent smokers to quit the habit

Pet exposure and risk of atopic dermatitis at the pediatric age: A meta-analysis of birth cohort studies

Background: Findings on pet exposure and the risk of atopic dermatitis (AD) in children are inconsistent. Objective: With the aim to summarize the results of exposure to different pets on AD, we undertook a meta-analysis of epidemiologic studies on this issue. Methods: In August 2012, we conducted a systematic literature search in Medline and Embase. We included analytic studies considering exposure to dogs, cats, other pets, or pets overall during pregnancy, infancy, and/or childhood, with AD assessment performed during infancy or childhood. We calculated summary relative risks and 95% CIs using both fixed- and random-effects models. We computed summary estimates across selected subgroups. Results: Twenty-six publications from 21 birth cohort studies were used in the meta-analyses. The pooled relative risks of AD for exposure versus no exposure were 0.72 (95% CI, 0.61-0.85; I2 = 46%; results based on 15 studies) for exposure to dogs, 0.94 (95% CI, 0.76-1.16; I2 = 54%; results based on 13 studies) for exposure to cats, and 0.75 (95% CI, 0.67-0.85; I2 = 54%; results based on 11 studies) for exposure to pets overall. No heterogeneity emerged across the subgroups examined, except for geographic area. Conclusion: This meta-analysis reported a favorable effect of exposure to dogs and pets on the risk of AD in infants or children, whereas no association emerged with exposure to cats. \ua9 2013 American Academy of Allergy, Asthma & Immunology

InP/ZnS as a safer alternative to CdSe/ZnS core/shell quantum dots: in vitro and in vivo toxicity assessment

We show that water soluble InP/ZnS core/shell QDs are a safer alternative to CdSe/ZnS QDs for biological applications, by comparing their toxicity in vitro (cell culture) and in vivo (animal model Drosophila). By choosing QDs with comparable physical and chemical properties, we find that cellular uptake and localization are practically identical for these two nanomaterials. Toxicity of CdSe/ZnS QDs appears to be related to the release of poisonous Cd(2+) ions and indeed we show that there is leaching of Cd(2+) ions from the particle core despite the two-layer ZnS shell. Since an almost identical amount of In(III) ions is observed to leach from the core of InP/ZnS QDs, their very low toxicity as revealed in this study hints at a much lower intrinsic toxicity of indium compared to cadmium

The Nordic Nutrition Recommendations and prostate cancer risk in the Cancer of the Prostate in Sweden (CAPS) study.

AbstractObjectiveThe Nordic Nutrition Recommendations (NNR) aim at preventing diet-associated diseases such as cancer in the Nordic countries. We evaluated adherence to the NNR in relation to prostate cancer (PC) in Swedish men, including potential interaction with a genetic risk score and with lifestyle factors.DesignPopulation-based case–control study (Cancer of the Prostate in Sweden (CAPS), 2001–2002). Using data from a semi-quantitative FFQ, we created an NNR adherence score and estimated relative risks of PC by unconditional logistic regression. Individual score components were modelled separately and potential modifying effects were assessed on the multiplicative scale.SettingFour regions in the central and northern parts of Sweden.SubjectsIncident PC patients (n 1386) and population controls (n 940), frequency-matched on age and region.ResultsNo overall association with PC was found, possibly due to the generally high adherence to the NNR score and its narrow distribution in the study population. Among individual NNR score components, high compared with low intakes of polyunsaturated fat were associated with an increased relative risk of localized PC. No formal interaction with genetic or lifestyle factors was observed, although in stratified analysis a positive association between the NNR and PC was suggested among men with a high genetic risk score but not among men with a medium or low genetic risk score.ConclusionsOur findings do not support an association between NNR adherence and PC. The suggestive interaction with the genetic risk score deserves further investigations in other study populations

Mediterranean Diet Score and prostate cancer risk in a Swedish population-based case–control study

Several individual components of the Mediterranean diet have been shown to offer protection against prostate cancer. The present study is the first to investigate the association between adherence to the Mediterranean diet and the relative risk of prostate cancer. We also explored the usefulness of the Mediterranean Diet Score (MDS) in a non-Mediterranean population. FFQ data were obtained from 1482 incident prostate cancer patients and 1108 population-based controls in the Cancer of the Prostate in Sweden (CAPS) study. We defined five MDS variants with different components or using either study-specific intakes or intakes in a Greek reference population as cut-off values between low and high intake of each component. Unconditional logistic regression was used to estimate the relative risk of prostate cancer for high and medium v. low MDS, as well as potential associations with the individual score components. No statistically significant association was found between adherence to the Mediterranean diet based on any of the MDS variants and prostate cancer risk (OR range: 0·96–1·19 for total prostate cancer, comparing high with low adherence). Overall, we found little support for an association between the Mediterranean diet and prostate cancer in this Northern European study population. Despite potential limitations inherent in the study or in the build-up of a dietary score, we suggest that the original MDS with study-specific median intakes as cut-off values between low and high intake is useful in assessing the adherence to the Mediterranean diet in non-Mediterranean populations

The Lantern Vol. 55, No. 1, Fall 1988

• The Third Grade Gorilla • Friend, I Am Not Yet A Poet • Twisted • The Final Journey • Ritu Miltonis • Hearthside • The Ogre • O Indestructible Everlasting • December 1, 1988 • Our Church • Louise • Gazebo For Learned Women • Hanging Mirror • Of Football and Flashlights • The Ragged Brown Peasant • Judgement of the Serpent • Sidewalk Wars • I Guess That\u27s Why I Went Awayhttps://digitalcommons.ursinus.edu/lantern/1133/thumbnail.jp

MicroRNA 199b-5p delivery through stable nucleic acid lipid particles (SNALPs) in tumorigenic cell lines

MicroRNA (miR)-199b-5p has been shown to regulate Hes-1, a downstream effector of the canonical Notch and noncanonical SHH pathways, whereby it impairs medulloblastoma (MB) cancer stem cells (CSCs) through a decrease in the CD133+/CD15+ cell population. Here, we have developed stable nucleic acid lipid particles (SNALPs) that encapsulate miR-199b-5p. The efficacy of the miR- 199b-5p delivery by these SNALPs is demonstrated by significant impairment of Hes-1 levels and CSC markers in a range of different tumorigenic cell lines: colon (HT- 29, CaCo-2, and SW480), breast (MDA-MB231T and MCF-7), prostate (PC-3), glioblastoma (U-87), and MB(Daoy, ONS-76, and UW-228). After treatment with SNALP miR-199b-5p, there is also impairment of cell pro- liferation and no signs of apoptosis, as measured by cas- pases 3/7 activity and annexin V fluorescence cell sorter analyses. These data strengthen the importance of such carriers for miRNA delivery, which show no cytotoxic effects and provide optimal uptake into cells. Thus, efficient target downregulation in different tumorigenic cell lines will be the basis for future preclinical studies