Expanding and Enriching the LncRNA Gene-Disease Landscape Using the GeneCaRNA Database.

The GeneCaRNA human gene database is a member of the GeneCards Suite. It presents ~280,000 human non-coding RNA genes, identified algorithmically from ~690,000 RNAcentral transcripts. This expands by ~tenfold the ncRNA gene count relative to other sources.

The Rise of Boron-Containing Compounds: Advancements in Synthesis, Medicinal Chemistry, and Emerging Pharmacology.

Boron-containing compounds (BCC) have emerged as important pharmacophores. To date, five BCC drugs (including boronic acids and boroles) have been approved by the FDA for the treatment of cancer, infections, and atopic dermatitis, while some natural BCC are included in dietary supplements. Boron's Lewis acidity facilitates a mechanism of action via formation of reversible covalent bonds within the active site of target proteins.

Small-Molecule Phosphine Activation of Protein Function in Zebrafish Embryos with an Expanded Genetic Code.

Conditional control of protein function in a living model organism is an important tool for studying the effects of that protein during development and disease. In this chapter, we walk through the steps to generate a small-molecule-activatable enzyme in zebrafish embryos through the incorporation of a noncanonical amino acid into the protein active site. This method can be applied to many enzyme classes, which we highlight with temporal control of a luciferase and a protease.

Chemically Acylated tRNAs are Functional in Zebrafish Embryos.

Genetic code expansion has pushed protein chemistry past the canonical 22 amino acids. The key enzymes that make this possible are engineered aminoacyl tRNA synthetases. However, as the number of genetically encoded amino acids has increased over the years, obvious limits in the type and size of novel side chains that can be accommodated by the synthetase enzyme become apparent.

Parallel publication of articles and congress presentations for industry-sponsored research: strategies for success.

Recent increases in the practice of parallel publication, during which a peer-reviewed manuscript is published concurrently with the first dissemination of the same key data at a medical congress as a late-breaking abstract, have highlighted substantial value for this method of publication. Parallel publication can increase access to new clinical information for healthcare providers and patients, as well as promote engagement and reach of the publication and presentation. As the practice becomes more common, there is a need for strategies to address the multiple challenges involved in the development process, such as shortened timelines, journal and congress policies, and stakeholder alignment.

(Un)ethical consequences: How psychology's cold war defense of military personnel led to enhanced interrogation techniques in the war on terror.

Cold War interrogation scholarship generated a research literature that included many prominent 20th century psychologists. The return of Korean War prisoners, many of whom had confessed falsely or otherwise collaborated with the enemy during confinement, amplified the intense anti-Communist fears of the Cold War. These events prompted substantial military and other government responses.

Organocatalytic trans Phosphinoboration of Internal Alkynes.

We report the first trans phosphinoboration of internal alkynes. With an organophosphine catalyst, alkynoate esters and the phosphinoboronate Ph P-Bpin are efficiently converted into the corresponding trans-α-phosphino-β-boryl acrylate products in moderate to good yield with high regio- and Z-selectivity. This reaction operates under mild conditions and demonstrates good atom economy, requiring only a modest excess of the phosphinoboronate.

Effect of age and race on quality of life in young breast cancer survivors.

Background: Given their early age at diagnosis, young breast cancer survivors (YBCSs) face issues that differ widely from their older counterparts.

Patients And Methods: We mailed a survey to 2209 patients who were ≤ 45 years at the time of breast cancer (BC) diagnosis. Each survey was composed of the Quality of Life in Adult Cancer Survivors instrument, Menopause Symptom Scale, and questions aimed at obtaining pertinent background information.

Pegylated leptin antagonist with strong orexigenic activity in mice is not effective in chickens.

A chicken gene orthologous to human leptin receptor (LEPR) has been characterized and found to be active in leptin signaling in vitro in response to a variety of recombinant leptins and leptin-containing blood samples. However, the endogenous ligand of chicken LEPR (cLEPR) - the putative chicken leptin - has been reported by us and others to be undetectable at the DNA, mRNA, protein and activity levels. These reports have raised questions as to cLEPR's role.

A miniaturized homogenous assay of mitochondrial membrane potential.

Mitochondrial dysfunction is increasingly associated with disease states. These organelles, responsible for adenosine triphosphate production, have been targeted for improved function in such diseases as Parkinson's, Alzheimer's, type 2 diabetes, and sarcopenia. In addition, the importance of determining if a clinical drug candidate adversely effects mitochondria function, which could lead to overt toxicity, has been recognized.

Apolipoprotein E4 domain interaction mediates detrimental effects on mitochondria and is a potential therapeutic target for Alzheimer disease.

Apolipoprotein (apo) E4 is the major genetic risk factor for late-onset Alzheimer disease (AD). ApoE4 assumes a pathological conformation through an intramolecular interaction mediated by Arg-61 in the amino-terminal domain and Glu-255 in the carboxyl-terminal domain, referred to as apoE4 domain interaction. Because AD is associated with mitochondrial dysfunction, we examined the effect of apoE4 domain interaction on mitochondrial respiratory function.

Lack of leptin activity in blood samples of Adélie penguin and bar-tailed godwit.

Unsuccessful attempts to identify the leptin gene in birds are well documented, despite the characterization of its receptor (LEPR). Since leptin and LEPR have poor sequence conservation among vertebrates, we speculated that a functional assay should represent the best way to detect leptin in birds. Using a leptin bioassay that is based on activation of the chicken LEPR in cultured cells, blood samples from wild birds with extreme seasonal variation in voluntary food intake and fat deposition (Adélie penguins and bar-tailed godwits) were tested for leptin activity.

Optimization of privileged structures for selective and potent melanocortin subtype-4 receptor ligands.

Design, syntheses and structure-activity relationships of N-acetylated piperazine privileged structures containing MC4R agonist compounds were described. The most potent derivatives were low nM MC4R selective full agonists. Several compounds from the series had modest pharmacokinetic properties.

Melanocortin potentiates leptin-induced STAT3 signaling via MAPK pathway.

The co-existence of receptors for leptin and melanocortin in cerebral microvessels suggests possible interactions between leptin and alpha-melanocyte stimulating hormone (MSH) signaling. In this study, we showed that ObRb and melanocortin receptor MC3R and MC4R were present in enriched cerebral microvessels. To test the interactions between ObRb and MC3R or MC4R-mediated cellular signaling, we over-expressed these plasmids in RBE4 cerebral microvascular endothelial cells and HEK293 cells in culture.

Monitoring leptin activity using the chicken leptin receptor.

We report on the construction of a leptin bioassay based on the activation of chicken leptin receptor in cultured cells. A human embryonic kidney (HEK)-293 cell line, stably transfected with the full-length cDNA of chicken leptin receptor together with a STAT3-responsive reporter gene specifically responded to recombinant human and Xenopus leptins. The observed higher sensitivity of chicken leptin receptor to the former is in agreement with the degree of sequence similarity among these species (about 60 and 38% identical amino acids between humans and chickens, and between humans and Xenopus respectively).

Randomized pilot test of a lifestyle physical activity intervention for breast cancer survivors.

Objective: This paper will report the results of a pilot test of a 6-month, 21-session intervention to increase breast cancer survivors' physical activity by teaching them to incorporate short periods of moderate activity into their daily routines (lifestyle intervention). The effect of the intervention on physical performance, quality of life, and physical activity are reported.

Methods: Sixty breast cancer survivors were randomized to either a lifestyle intervention or a standard care control group.

Discovery and activity of (1R,4S,6R)-N-[(1R)-2-[4-cyclohexyl-4-[[(1,1-dimethylethyl)amino]carbonyl]-1-piperidinyl]-1-[(4-fluorophenyl)methyl]-2-oxoethyl]-2-methyl-2-azabicyclo[2.2.2]octane-6-carboxamide (3, RY764), a potent and selective melanocortin subtype-4 receptor agonist.

A novel isoquinuclidine containing selective melanocortin subtype-4 receptor small molecule agonist, 3 (RY764), is reported. Its in vivo characterization revealed mechanism-based food intake reduction and erectile activity augmentation in rodents.

2-Piperazinecarboxamides as potent and selective melanocortin subtype-4 receptor agonists.

We report the discovery and optimization of substituted 2-piperazinecarboxamides as potent and selective agonists of the melanocortin subtype-4 receptor. The 5- and 6-alkylated piperazine compounds exhibit low bioactivation potential as measured by covalent binding in microsome preparations.

Discovery of (2S)-N-[(1R)-2-[4-cyclohexyl-4-[[(1,1-dimethylethyl)amino]carbonyl]-1-piperidinyl]-1-[(4-fluorophenyl)methyl]-2-oxoethyl]-4-methyl-2-piperazinecarboxamide (MB243), a potent and selective melanocortin subtype-4 receptor agonist.

We report the discovery and optimization of substituted 2-piperazinecarboxamides as potent and selective agonists of the melanocortin subtype-4 receptor. Further in vivo development of lead agonist, MB243, is disclosed.

Activation of MAP kinase by MC4-R through PI3 kinase.

The melanocortin 4 receptor (MC4-R) is a Galpha s-coupled receptor known to increase cAMP production following agonist stimulation. We demonstrate that the mitogen-activated protein kinases p42 (ERK2) and p44 (ERK1) are also activated by MC4-R following treatment with the MC4-R agonist NDP-alpha-MSH in stably transfected CHO-K1 cells. This time- and dose-dependent response is abolished by the MC4-R antagonist SHU-9119.

Design and syntheses of melanocortin subtype-4 receptor agonists: evolution of the pyridazinone archetype.

The discovery and optimization of a new class of non-peptidyl, pyridazinone derived melanocortin subtype-4 receptor agonists is disclosed.

Self-reported health status, health vulnerability, and smoking behavior in college students: implications for intervention.

Health-related factors, including prevalence of respiratory symptoms and perceived health status, were analyzed by smoking status and by stages of change for quitting to evaluate their potential use as motivators for tobacco cessation. Data were obtained from a survey of 1,283 Houston-area community college students. Respiratory symptoms were most frequent among current smokers and least frequent among never smokers.

Predictors of susceptibility to smoking and ever smoking: a longitudinal study in a triethnic sample of adolescents.

This report describes a longitudinal study of the natural course of smoking initiation in a school-based, ethnically diverse (42% White, 37% African American, 20% Hispanic) sample of adolescents in grades 5, 8, and 12 who were followed prospectively for 1 year. A cohort of 659 students was identified who were never smokers at baseline and who completed questionnaires both at baseline and at 1-year follow-up. From this cohort, predictor variables were used to identify ethnic-specific risk factors for (a) "susceptibility to smoking" among the 509 students who were nonsusceptible, never smokers at baseline and (b) "ever smoking" among all 659 students who were never smokers at baseline (both susceptible and nonsusceptible).

Serum leptin activity in obese and lean patients.

Blood levels of the satiety hormone leptin are directly correlated to fat stores in obese and lean people. Therefore, leptin resistance is the logical explanation for the phenomenon of common obesity. However, the important question of whether or not the intrinsic leptin activity could differ between obese and lean people has not been examined before.