Ligand Selectivity in the Recognition of Protoberberine Alkaloids by Hybrid-2 Human Telomeric G-Quadruplex: Binding Free Energy Calculation, Fluorescence Binding, and NMR Experiments.

The human telomeric G-quadruplex (G4) is an attractive target for developing anticancer drugs. Natural products protoberberine alkaloids are known to bind human telomeric G4 and inhibit telomerase. Among several structurally similar protoberberine alkaloids, epiberberine (EPI) shows the greatest specificity in recognizing the human telomeric G4 over duplex DNA and other G4s.

Assessing Vaccine Contraindications Through the Use of the Immunization Action Coalition Screening Checklist.

Immunization action coalition (IAC) provides a checklist that occupational health nurses use to screen for vaccine contraindications to identify and prevent possible adverse effects.

Leveraging Horizontal Density Differences between Ontologies to Identify Missing Child Concepts: A Proof of Concept.

Previously, we investigated pairs of ontologies with local similarities where corresponding "is-a" paths are of different lengths. This indicated the possibility of importing concepts from one ontology into the other. We referred to such structures as diamonds of concepts.

Workspace Disorder Does Not Influence Creativity and Executive Functions.

Recent research by Vohs et al. (2013) garnered media attention after reporting that disordered environments increase creativity. The present research was designed to conceptually replicate and extend this finding by exploring the effect of workspace disorder on creativity.

New Dopamine D3-Selective Receptor Ligands Containing a 6-Methoxy-1,2,3,4-tetrahydroisoquinolin-7-ol Motif.

A series of analogues featuring a 6-methoxy-1,2,3,4-tetrahydroisoquinolin-7-ol unit as the arylamine "head" group of a classical D3 antagonist core structure were synthesized and evaluated for affinity at dopamine D1, D2, and D3 receptors (D1R, D2R, D3R). The compounds generally displayed strong affinity for D3R with very good D3R selectivity. Docking studies at D2R and D3R crystal structures revealed that the molecules are oriented such that their arylamine units are positioned in the orthosteric binding pocket of D3R, with the arylamide "tail" units residing in the secondary binding pocket.

Griffithsin carrageenan fast dissolving inserts prevent SHIV HSV-2 and HPV infections in vivo.

Human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) strategies with proven in vivo efficacy rely on antiretroviral drugs, creating the potential for drug resistance and complicated treatment options in individuals who become infected. Moreover, on-demand products are currently missing from the PrEP development portfolio. Griffithsin (GRFT) is a non-antiretroviral HIV entry inhibitor derived from red algae with an excellent safety profile and potent activity in vitro.

Oxygen-Promoted Chemical Vapor Deposition of Graphene on Copper: A Combined Modeling and Experimental Study.

Mass production of large, high-quality single-crystalline graphene is dependent on a complex coupling of factors including substrate material, temperature, pressure, gas flow, and the concentration of carbon and hydrogen species. Recent studies have shown that the oxidation of the substrate surface such as Cu before the introduction of the C precursor, methane, results in a significant increase in the growth rate of graphene while the number of nuclei on the surface of the Cu substrate decreases. We report on a phase-field model, where we include the effects of oxygen on the number of nuclei, the energetics at the growth front, and the graphene island morphology on Cu.

Detecting Protein Subcellular Localization by Green Fluorescence Protein Tagging and 4',6-Diamidino-2-phenylindole Staining in Caenorhabditis elegans.

In this protocol, a green fluorescence protein (GFP) fusion protein and 4',6-diamidino-2-phenylindole (DAPI) staining are used to track protein subcellular localization changes; in particular, a nuclear translocation under a heat stress condition. Proteins react correspondingly to external and internal signals. A common mechanism is to change its subcellular localization.

Development of a Vaginal Fast-Dissolving Insert Combining Griffithsin and Carrageenan for Potential Use Against Sexually Transmitted Infections.

Precoital, on-demand topical microbicides to reduce a woman's risk of sexually transmitted infections have been in development for nearly 3 decades, but no product has been approved due to acceptability issues and poor adherence in clinical trials. We set out to develop a self-administered vaginal fast-dissolving insert (FDI) produced by freeze-drying that would deliver safe and effective amounts of the antiviral agents griffithsin (GRFT) and carrageenan (CG) and would have properties women and their partners find acceptable. We evaluated FDI physical criteria, attributes of the gel produced upon dissolving, and GRFT stability.

Complex overlapping concepts: An effective auditing methodology for families of similarly structured BioPortal ontologies.

In previous research, we have demonstrated for a number of ontologies that structurally complex concepts (for different definitions of "complex") in an ontology are more likely to exhibit errors than other concepts. Thus, such complex concepts often become fertile ground for quality assurance (QA) in ontologies. They should be audited first.

Prenatal exposure to disaster-related traumatic stress and developmental trajectories of temperament in early childhood: Superstorm Sandy pregnancy study.

Background: Little is known about the impact of prenatal maternal stress (PNMS) on the developmental trajectory of temperament and few studies have been able to incorporate a natural disaster as a quasi-experimental stressor. The current study investigated PNMS related to Superstorm Sandy ('Sandy'), a hurricane that struck the New York metropolitan area in October 2012, in terms of objective exposure during pregnancy, subjective stress reaction as assessed by maternal symptoms of post-traumatic stress, and their impact on the developmental changes in temperament during early childhood.

Method: A subsample of 318 mother-child dyads was drawn from the Stress in Pregnancy Study.

Working Memory and Consciousness: The Current State of Play.

Working memory (WM), an important posit in cognitive science, allows one to temporarily store and manipulate information in the service of ongoing tasks. WM has been traditionally classified as an explicit memory system-that is, as operating on and maintaining only consciously perceived information. Recently, however, several studies have questioned this assumption, purporting to provide evidence for unconscious WM.

" Former Soviet Union Mothers' Beliefs about Autonomy Development.

This qualitative study examined Former Soviet Union (FSU) mothers' explicit and implicit attitudes and parenting practices around adolescents' autonomy development. Interviews were conducted with 10 mothers who had immigrated from the FSU to the US between 10 and 25 years ago, and who had daughters between the ages of 13 and 17 years. Mothers predominantly defined autonomy in terms of adolescents' ability to carry out instrumental tasks, make correct decisions, and financially provide for themselves, but rarely mentioned psychological or emotional independence.

The gravity of an edge.

We describe a methodology for characterizing the relative structural importance of an arbitrary network edge by exploiting the properties of a -shortest path algorithm. We introduce the metric , measuring how often an edge occurs in any possible network path, as well as -Gravity, a lower bound based on paths enumerated while solving the -shortest path problem. The methodology is demonstrated using Granovetter's original network examples as well as the well-known Florentine families of the Italian Renaissance and the Krebs 2001 terrorist networks.

Using Facebook as a Platform to Direct Young Black Men Who Have Sex With Men to a Video-Based HIV Testing Intervention: A Feasibility Study.

Objective: A randomized control pilot study was conducted with Black men who have sex with men (BMSM; = 42) aged 18-30 years to examine the feasibility of implementing a video intervention delivered using Facebook to motivate HIV testing.

Methods: At baseline, participants were unaware of their HIV status and had not tested for HIV in the past 6 months, residing in Los Angeles County. The intervention content included topics such as social influence, HIV knowledge, stigma, HIV positive knowledge, and benefits of knowing one's HIV status.

Addressing the Antinomy Between Health Education and Health Literacy in Advancing Personal Health and Public Health Outcomes.

Background: Health literacy evolved from a standard of English language proficiency designed to promote patient compliance into an inferential for promoting positive health decision-making and health outcomes. In turn, the United States relegated health literacy as a national strategy to improve personal health and health care outcomes as well as reduce national health care expenditures.

Methods: We reviewed the literature to assess the empirical research about health literacy and health behavior and health status outcomes.

Resolving the Ligand-Binding Specificity in c-MYC G-Quadruplex DNA: Absolute Binding Free Energy Calculations and SPR Experiment.

We report the absolute binding free energy calculation and surface plasmon resonance (SPR) experiment for ligand binding with the c-MYC G-quadruplex DNA. The unimolecular parallel DNA G-quadruplex formed in nuclease hypersensitivity element III of the c-MYC gene promoter regulates the c-MYC transcription and is recognized as an emerging drug target for cancer therapy. Quindoline derivatives have been shown to stabilize the G-quadruplex and inhibit the c-MYC expression in cancer cells.

Preschool Predictors of ADHD Symptoms and Impairment During Childhood and Adolescence.

Purpose Of Review: This paper summarizes key, recently published research examining longitudinal outcomes for preschoolers with high levels of inattention and/or hyperactivity/impulsivity.

Recent Findings: Symptom trajectories show that hyperactivity/impulsivity declines across childhood. At the group level, the course of inattention appears more variable.

A first linkage map and downy mildew resistance QTL discovery for sweet basil (Ocimum basilicum) facilitated by double digestion restriction site associated DNA sequencing (ddRADseq).

Limited understanding of sweet basil (Ocimum basilicum L.) genetics and genome structure has reduced efficiency of breeding strategies. This is evidenced by the rapid, worldwide dissemination of basil downy mildew (Peronospora belbahrii) in the absence of resistant cultivars.

Chloride intracellular channel proteins respond to heat stress in Caenorhabditis elegans.

Chloride intracellular channel proteins (CLICs) are multi-functional proteins that are expressed in various cell types and differ in their subcellular location. Two CLIC homologs, EXL-1 (excretory canal abnormal like-1) and EXC-4 (excretory canal abnormal- 4), are encoded in the Caenorhabditis elegans genome, providing an excellent model to study the functional diversification of CLIC proteins. EXC-4 functions in excretory canal formation during normal animal development.

MIV-150 and zinc acetate combination provides potent and broad activity against HIV-1.

We previously showed that the combination of the non-nucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 with zinc acetate (ZA) formulated in a carrageenan (CG; MZC) gel provided macaques significant protection against vaginal simian-human immunodeficiency virus-RT (SHIV-RT) challenge, better than either MIV-150/CG or ZA/CG. The MZC gel was shown to be safe in a phase 1 clinical trial. Herein, we used in vitro approaches to study the antiviral properties of ZA and the MIV-150/ZA combination, compared to other NNRTIs.

Pixuna virus modifies host cell cytoskeleton to secure infection.

Pixuna virus (PIXV) is an enzootic member of the Venezuelan Equine Encephalitis Virus complex and belongs to the New World cluster of alphaviruses. Herein we explore the role of the cellular cytoskeleton during PIXV replication. We first identified that PIXV undergoes an eclipse phase consisting of 4 h followed by 20 h of an exponential phase in Vero cells.

An intravaginal ring that releases three antiviral agents and a contraceptive blocks SHIV-RT infection, reduces HSV-2 shedding, and suppresses hormonal cycling in rhesus macaques.

Women globally need access to multipurpose prevention technologies (MPTs) that prevent human immunodeficiency virus (HIV), sexually transmitted infections that increase HIV acquisition/transmission risk, and unintended pregnancy. Seeking an MPT with activity against HIV, herpes simplex virus-2 (HSV-2), and human papillomavirus (HPV), we developed a prototype intravaginal ring (IVR), the MZCL IVR, which released the antiviral agents MIV-150, zinc acetate, and carrageenan (MZC for short) and the contraceptive levonorgestrel (LNG). Previously, we showed that an MZC gel has potent activity against immunodeficiency viruses, HSV-2, and HPV and that the MZCL (MZC with LNG) IVR releases all four components in macaques in vivo at levels associated with efficacy.