Gold nanoparticles: the importance of physiological principles to devise strategies for targeted drug delivery.

Nanotechnology and its promise for clinical translation to targeted drug delivery with limited accompanying toxicity provide exciting research opportunities that demand multidisciplinary approaches. To make rapid progress in the design of nano-platforms for drug delivery and toward their use in the clinic, basic and mechanistic studies must first be tested in vitro and then progress to in vivo studies in animal models, incorporating an understanding of body functioning. Recently, gold nanoparticles (Au NPs) have gained much attention as model drug delivery platforms because of their advantageous surface characteristics that allow easy functionalization with chemical and biological molecules and also due to their apparently low toxicity.

Mechanisms of Yin Yang 1 in oncogenesis: the importance of indirect effects.

Yin Yang 1 (YY1) is a ubiquitously expressed transcription factor that performs numerous functions including transcriptional regulation, cell growth control, apoptosis, large-scale chromosomal dynamics, and X-chromosome inactivation. YY1 clearly is able to control cell functions, including proliferation, by acting as a transcription factor either to activate or repress specific genes. Based on its ability to regulate cell growth control genes, it has been argued that YY1 can function as an oncogene that initiates oncogenesis.

Gold-peptide nanoconjugate cellular uptake is modulated by serum proteins.

Gold nanoparticles (Au NPs, 20 nm) were conjugated with two different cysteine-terminated peptides. Radio-ligand binding studies were conducted to characterize Au NP-peptide binding, suggesting both covalent and noncovalent interactions. The interactions of serum proteins with Au NP-peptide nanoconjugates were determined using gel electrophoresis and dynamic light scattering.

Glowing locked nucleic acids: brightly fluorescent probes for detection of nucleic acids in cells.

Fluorophore-modified oligonucleotides have found widespread use in genomics and enable detection of single-nucleotide polymorphisms, real-time monitoring of PCR, and imaging of mRNA in living cells. Hybridization probes modified with polarity-sensitive fluorophores and molecular beacons (MBs) are among the most popular approaches to produce hybridization-induced increases in fluorescence intensity for nucleic acid detection. In the present study, we demonstrate that the 2'-N-(pyren-1-yl)carbonyl-2'-amino locked nucleic acid (LNA) monomer X is a highly versatile building block for generation of efficient hybridization probes and quencher-free MBs.

Sexual dimorphism in hepatic gene expression and the response to dietary carbohydrate manipulation in the zebrafish (Danio rerio).

In this study, we tested for the presence of sexual dimorphism in the hepatic transcriptome of the adult zebrafish and examined the effect of long term manipulation of dietary carbohydrate on gene expression in both sexes. Zebrafish were fed diets comprised of 0%, 15%, 25%, or 35% carbohydrate from the larval stage through sexual maturity, then sampled for hepatic tissue, growth, proximate body composition, and retention efficiencies. Using Affymetrix microarrays and qRT-PCR, we observed substantial sexual dimorphism in the hepatic transcriptome.

Early developmental expression of two insulins in zebrafish (Danio rerio).

We have cloned a second insulin gene in zebrafish and studied temporal and spatial expression of two zebrafish insulin genes. Zebrafish insulin-a (insa) and -b (insb) mRNAs are derived from two different DNA contigs on chromosomes 5 and 14, respectively, representing two different insulin genes. Real-time PCR studies suggest that insa is a maternal and also a postzygotic transcript.

Identification and characterization of the zebrafish and fugu genes encoding tuberoinfundibular peptide 39.

Although the PTH type 2 receptor (PTH2R) has been isolated from mammals and zebrafish, only its mammalian agonist, tuberoinfundibular peptide 39 (TIP39), has been characterized thus far. To determine whether zebrafish TIP39 (zTIP39) functions similarly with the zebrafish PTHR (zPTH2R) and human PTH2Rs and to determine its tissue-specific expression, fugu (Takifugu rubripes) and zebrafish (Danio rerio) genomic databases were screened with human TIP39 (hTIP39) sequences. A single TIP39 gene was identified for each fish species, which showed significant homology to mammalian TIP39.

Identification and characterization of two parathyroid hormone-like molecules in zebrafish.

Zebrafish (Danio rerio) have receptors homologous to the human PTH (hPTH)/PTHrP receptor (PTH1R) and PTH-2 receptor (PTH2R) and an additional receptor (PTH3R) with high homology to the PTH1R. To find natural ligands for zPTH1R and zPTH3R, we searched the zebrafish genomic database and discovered two distinct regions that, when translated (zPTH1 and zPTH2), showed high homology to hPTH. Isolation of cDNAs and determination of the intron/exon boundaries revealed genomic structures which were similar to known PTHs.