G4 resolvase 1 binds both DNA and RNA tetramolecular quadruplex with high affinity and is the major source of tetramolecular quadruplex G4-DNA and G4-RNA resolving activity in HeLa cell lysates.

Quadruplex structures that result from stacking of guanine quartets in nucleic acids possess such thermodynamic stability that their resolution in vivo is likely to require specific recognition by specialized enzymes. We previously identified the major tetramolecular quadruplex DNA resolving activity in HeLa cell lysates as the gene product of DHX36 (Vaughn, J. P.

Risk perception and water purification practices for water-borne parasitic infections in remote Nepal.

This study assesses water-borne infection risk perception and water boiling habits in a remote Sankhuwasava region of Nepal using a brief interview-style questionnaire. All subjects were aware of the risks associated with drinking unpurified water, but a majority (65%) reported they did not boil water regularly, and almost 60% of villagers interviewed had history of infection despite their boiling practices. In contrast to reports from other communities in Nepal, risk awareness was sufficient in this region.

Strength training recommendations for the young athlete.

In recent years there has been a significant increase in the number of youth participating in organized and competitive sports. Recent studies have supported the participation of preadolescent athletes in strength training to improve health and performance in sports. This article presents the most recent data available to help youth develop a safe and effective strength training program.

The effect of cigarette price increases on smoking cessation in California.

We investigated whether smoking cessation increased in California after a cigarette manufacturer's retail price increase and an increase in the state cigarette excise tax. The sample for this study was drawn from the 1996 and 1999 California Tobacco Surveys. The rate of unsuccessful and successful quit attempts and the rate of abstinence were calculated for each month of the 14-month period preceding each survey administration.

Nicotine effects on affective response in depression-prone smokers.

Rationale: Comorbidity between cigarette smoking and depression is thought to arise because depression-prone smokers self-administer nicotine to improve mood. Yet little evidence supports this view, and nicotine's effect on positive affect deficiency in depression remains largely unstudied.

Objectives: We hypothesized that (1) nicotine would dispel negative affect and enhance positive affect and (2) effects would be stronger for smokers vulnerable to depression, particularly during a depressed state.

Alternative splicing of an rnp-4f mRNA isoform retaining an evolutionarily-conserved 5'-UTR intronic element is developmentally regulated and shown via RNAi to be essential for normal central nervous system development in Drosophila melanogaster.

Two major mRNA isoforms arise via alternative splicing in the 5'-UTR of Drosophila splicing assembly factor rnp-4f pre-mRNA, designated "long" (unspliced) and "short" (alternatively spliced). The coding potential for the two isoforms is identical, raising interesting questions as to the control mechanism and functional significance of this 5'-UTR intronic splicing decision. Developmental Northerns show that two temporally distinct rnp-4f mRNA degradation episodes occur during embryogenesis.

On the functions of the h subunit of eukaryotic initiation factor 3 in late stages of translation initiation.

Background: The eukaryotic translation initiation factor 3 (eIF3) has multiple roles during the initiation of translation of cytoplasmic mRNAs. How individual subunits of eIF3 contribute to the translation of specific mRNAs remains poorly understood, however. This is true in particular for those subunits that are not conserved in budding yeast, such as eIF3h.

Murine airway histology and intracellular uptake of inhaled amorphous itraconazole.

Aerosolization of amorphous itraconazole may be a safe and effective method of pulmonary delivery. Our objective was to evaluate the histologic effects, immunogenic potential, and cellular uptake of aerosolized amorphous itraconazole. Mice received amorphous itraconazole (30mg/kg), excipient placebo, or saline control by nebulization every 12h for up to 12 days.

Atom-by-atom extraction using the scanning tunneling microscope tip-cluster interaction.

We investigate the atomistic details of a single atom-extraction process realized by using the scanning tunneling microscope tip-cluster interaction on a Ag(111) surface at 6 K. Single atoms are extracted from a silver cluster one atom at a time using small tunneling biases less than 35 mV. Combined total energy calculations and molecular dynamics simulations show a lowering of the atom-extraction barrier upon approaching the tip to the cluster.

Cryogenic liquids, nanoparticles, and microencapsulation.

The biopharmaceutical classification system (BCS) is used to group pharmaceutical actives depending upon the solubility and permeability characteristics of the drug. BCS class II compounds are poorly soluble but highly permeable, exhibiting bioavailability that is limited by dissolution. The dissolution rate of BCS class II drug substances may be accelerated by enhancing the wetting of the bulk powder and by reducing the primary particle size of the drug to increase the surface area.

Supersaturation produces high bioavailability of amorphous danazol particles formed by evaporative precipitation into aqueous solution and spray freezing into liquid technologies.

The bioavailability of high surface area danazol formulations was evaluated in a mouse model to determine what effect high supersaturation, as measured in vitro, has on the absorption of a poorly water soluble drug. Danazol, a biopharmaceutics classification system II (BCS II) compound, was used as the model drug. Evaporative precipitation into aqueous solution (EPAS) and spray freezing into liquid (SFL) technologies were used to prepare powders of danazol/PVP K-15 in a 1:1 ratio.

Targeted high lung concentrations of itraconazole using nebulized dispersions in a murine model.

Purpose: The purpose of this study was to investigate the delivery of itraconazole (ITZ) particles to a murine lung model by nebulization.

Methods: Three ITZ formulations were prepared and characterized in the dry state using contact angle, dissolution, X-ray powder diffraction, scanning electron microscopy, and Brunauer-Emmett-Teller surface area analysis. Aerodynamic particle size distributions and lung deposition studies in 14 outbred male ICR mice were performed using aqueous dispersions of all the formulations.

Further differentiation of murine double-positive thymocytes is inhibited in adenosine deaminase-deficient murine fetal thymic organ culture.

Murine fetal thymic organ culture (FTOC) was used to investigate the mechanism by which a lack of adenosine deaminase (ADA) leads to a failure of T cell production in the thymus. We previously showed that T cell development was inhibited beginning at the CD4(-)CD8(-)CD25(+)CD44(low) stage in ADA-deficient FTOC initiated at day 15 of gestation when essentially all thymocytes are CD4(-)CD8(-). In the present study, we asked whether thymocytes at later stages of differentiation would also be sensitive to ADA inhibition by initiating FTOC when substantial numbers of CD4(+)CD8(+) thymocytes were already present.

Single dose and multiple dose studies of itraconazole nanoparticles.

The objective of this study was to determine and compare the lung and serum concentrations in mice following oral and pulmonary dosing of amorphous nanoparticulate itraconazole (ITZ) compositions as well as the Sporanox oral solution (itraconazole/Janssen). Second, the steady state partitioning of ITZ in lung tissue and circulatory compartments following repeated oral and pulmonary dosing was determined. The pulmonary formulation (ITZ-pulmonary) consisted of ITZ, polysorbate 80, and poloxamer 407 in a 1:0.

Alternative pre-mRNA splicing in Drosophila spliceosomal assembly factor RNP-4F during development.

The 5'- and 3'-UTR regions in pre-mRNAs play a variety of roles in controlling eukaryotic gene expression, including translational modulation. Here we report the results of a systematic study of alternative splicing in rnp-4f, which encodes a Drosophila spliceosomal assembly factor. We show that most of the nine introns are constitutively spliced, but several patterns of alternative splicing are observed in two pre-mRNA regions including the 5'-UTR.

Moving: characteristics of dogs and cats and those relinquishing them to 12 U.S. animal shelters.

The National Council on Pet Population Study and Policy Regional Shelter Survey identified moving as the most often cited of 71 reasons for relinquishing dogs and the 3rd most common reason for relinquishing cats. Most relinquished companion animals were less than 3 years old and female. Dogs were most often intact, whereas cats were most often altered.

The effect of over-the-counter sales of the nicotine patch and nicotine gum on smoking cessation in California.

The Food and Drug Administration approved over-the-counter (OTC) sale of nicotine gum and nicotine patches in 1996. We used data from the 1996 California Tobacco Survey to compare the rates of nicotine replacement therapy (NRT) use and smoking abstinence in California for each month during a period immediately preceding and immediately following the OTC availability of nicotine gum and patches. For smokers eligible to report a quit attempt, the proportion making a quit attempt using NRT and the proportion remaining abstinent was calculated for each of the 12 months prior to the survey interview.

The DEXH protein product of the DHX36 gene is the major source of tetramolecular quadruplex G4-DNA resolving activity in HeLa cell lysates.

G4-DNA is a highly stable alternative DNA structure that can form spontaneously in guanine-rich regions of single-stranded DNA under physiological conditions. Since a number of biological processes create such single-stranded regions, G4-DNA occurrence must be regulated. To date, resolution of tetramolecular G4-DNA into single strands (G4-resolvase activity) has been observed only in recombinant RecQ DNA helicases.

Fetal oxygen tension promotes tenascin-C-dependent lung branching morphogenesis.

Tenascin-C (TN-C) is a mesenchyme-derived extracellular matrix (ECM) glycoprotein required for fetal lung branching morphogenesis. Given that the low oxygen (O(2)) environment of the fetus is also essential for normal lung branching morphogenesis, we determined whether fetal O(2) tension supports this process by promoting TN-C expression. Initial studies showed that 15-day fetal rat lung explants cultured for 2 days at 3% O(2) not only branched well, but they also expressed higher levels of TN-C when compared to lungs maintained at 21% O(2), which branched poorly.

Transcobalamin 776C->G polymorphism negatively affects vitamin B-12 metabolism.

Background: A common genetic polymorphism [transcobalamin (TC) 776C-->G] may affect the function of transcobalamin, the protein required for vitamin B-12 cellular uptake and metabolism. Remethylation of homocysteine is dependent on the production of 5-methyltetrahydrofolate and adequate vitamin B-12 for the methionine synthase reaction.

Objectives: The objectives were to assess the influence of the TC 776C--> G polymorphism on concentrations of the transcobalamin-vitamin B-12 complex (holo-TC) and to determine the combined effects of the TC 776C-->G and methylenetetrahydrofolate reductase (MTHFR) 677C-->T polymorphisms and vitamin B-12 status on homocysteine concentrations.

Comparison of powder produced by evaporative precipitation into aqueous solution (EPAS) and spray freezing into liquid (SFL) technologies using novel Z-contrast STEM and complimentary techniques.

The objective of this study was to compare the properties of particles formed by nucleation and polymer stabilization (e.g. evaporative precipitation into aqueous solution (EPAS)) versus rapid freezing (e.

Stability of the topoisomerase II closed clamp conformation may influence DNA-stimulated ATP hydrolysis.

Type II DNA topoisomerases catalyze changes in DNA topology and use nucleotide binding and hydrolysis to control conformational changes required for the enzyme reaction. We examined the ATP hydrolysis activity of a bisdioxopiperazine-resistant mutant of human topoisomerase II alpha with phenylalanine substituted for tyrosine at residue 50 in the ATP hydrolysis domain of the enzyme. This substitution reduced the DNA-dependent ATP hydrolysis activity of the mutant protein without affecting the relaxation activity of the enzyme.

Methionine synthase reductase 66A->G polymorphism is associated with increased plasma homocysteine concentration when combined with the homozygous methylenetetrahydrofolate reductase 677C->T variant.

Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) are important for homocysteine remethylation. This study was designed to determine the influence of genetic variants (MTHFR 677C-->T, MTHFR 1298A-->C, and MTRR 66A-->G), folate, and vitamin B-12 status on plasma homocysteine in women (20-30 y; n = 362). Plasma homocysteine was inversely (P < 0.