generation-zerovalent-metal-core-nanoparticles-using-n-2-aminoethyl-3

Generation of Zerovalent Metal Core Nanoparticles Using n-(2-aminoethyl)-3-aminosilanetriol

In this work, a facile one-pot reaction for the formation of metal nanoparticles in a water solution through the use of ...

William Paterson University

We have utilized a computational structure-based approach to identify nonpeptidic small organic compounds that bind to a human leukocyte antigen (HLA) DR1301 molecule (HLA-DR1301 or DR1301) and block the presentation of myelin basic protein peptide 152-165 (MBP 152-165) to T cells. A three-dimensional (3D) structure of DR1301 was derived by homology modeling followed by extensive molecular dynamics simulation for structural refinement. Computational structure-based database searching was performed to identify nonpeptidic small-molecule candidates from the National Cancer Institute (NCI) database containing over 150 000 compounds that can effectively interact with the peptide-binding groove of the HLA molecule. By in vitro testing of 106 candidate small molecules, two lead compounds were confirmed to specifically block IL-2 secretion by DR1301-restricted T cells in a dose-dependent and reversible manner. The specificity of blocking DR1301-restricted MBP presentation was further validated in a binding assay using an analogue of the most potent lead compound. Computational docking was performed to predict the three-dimensional binding model of these confirmed small molecule blockers to the DR1301 molecule and to gain structural insight into their interactions. Our results suggest that computational structure-based searching is an effective approach to discover nonpeptidic small organic compounds to block the interaction between DR1301 and T cells. The nonpeptidic small organic compounds identified in this study are useful pharmacological tools to study the interactions between HLA molecules and T cells and a starting point for the development of a novel therapeutic strategy for the treatment of multiple sclerosis (MS) or other immune-related disorders.

Structure-based discovery of nonpeptidic small organic compounds to block the T cell response to myelin basic protein.

The human transcription factor Sp3 has been widely studied at the translational level and has been described as a regulatory factor for a number of genes. Sp3 is currently characterized as a bifunctional transcription factor having the ability to behave as both an activator and/or a repressor in various promoter regions. Previous translational studies have attempted to determine the basis for these diverse functions with mostly contradictory evidence to date. Little data are available, however, concerning genomic structure, full-length cDNA, potential transcript variants, or location of translation initiation sites for the large isoform of the Sp3 gene. In this study, bacterial artificial chromosome (BAC) sequencing, reverse transcription-polymerase chain reaction (RT-PCR), genomic PCR, and database mining indicate that the Sp3 gene encompasses seven exons spanning more than 55 kb of genomic DNA on Chromosome 2. The 5' end of this sequence contains a large CpG island. This work also detected a processed pseudogene, psiSp3, located on Chromosome 13, spanning approximately 4.0 kb. Northern blot analysis detected three predominant transcripts at 4.0, 6.0 and 2.5 kb. Sequence analysis indicated that alternative splicing of exon 3 allows for multiple transcripts of Sp3. Each sequenced transcript possesses three to five potential translation initiation sites. This diversity at the level of gene expression will likely be key to understanding the diverse functions of Sp3.

Human transcription factor Sp3: genomic structure, identification of a processed pseudogene, and transcript analysis.

The silencing of gene expression through DNA methylation contributes to defects in antigen presentation and apoptosis in melanoma and renal cell cancer. To determine how a hypomethylating agent would modulate the toxicity and antitumor activity of immunotherapy, we initiated a phase I trial of 5-aza-2'-deoxycytidine (decitabine) plus high-dose interleukin 2 (IL-2).

Phase I trial of sequential low-dose 5-aza-2'-deoxycytidine plus high-dose intravenous bolus interleukin-2 in patients with melanoma or renal cell carcinoma.

Increasing patient volume and residents' work hour restrictions have increased the workload at trauma centers. Further, comprehensive tertiary surveys after initial stabilization and appropriate follow-up plans for incidental findings are time consuming. Midlevel providers (MLP) can help streamline this process. We initiated a care plan in which MLPs conducted all tertiary surveys and coordinated follow-ups for incidental findings.

Optimal management strategy for incidental findings in trauma patients: an initiative for midlevel providers.

The potential for storing additional C in U.S. Corn Belt soils - to offset rising atmospheric [CO(2)] - is large. Long-term cultivation has depleted substantial soil organic matter (SOM) stocks that once existed in the region's native ecosystems. In central Illinois, free-air CO(2) enrichment technology was used to investigate the effects of elevated [CO(2)] on SOM pools in a conservation tilled corn-soybean rotation. After 5 and 6 y of CO(2) enrichment, we investigated the distribution of C and N among soil fractions with varying ability to protect SOM from rapid decomposition. None of the isolated C or N pools, or bulk-soil C or N, was affected by CO(2) treatment. However, the site has lost soil C and N, largely from unprotected pools, regardless of CO(2) treatment since the experiment began. These findings suggest management practices have affected soil C and N stocks and dynamics more than the increased inputs from CO(2)-stimulated photosynthesis.

Elevated carbon dioxide does not offset loss of soil carbon from a corn-soybean agroecosystem.

Increased patient volume and residents' work hour restrictions have escalated the workload at trauma centers. Because tertiary surveys (TSs) are integral to care, midlevel providers (MLPs) can help streamline this time-consuming process. In this study, we implemented a care plan in which MLPs conduct all TSs, initiate appropriate consultations, and offload residents' work hours.

An initiative by midlevel providers to conduct tertiary surveys at a level I trauma center.

Reported herein is the use of chiral cationic polyamines for two intriguing applications: fabrication of chiral covalently-linked microcapsules, and enantiospecific delivery of siRNA to Huh 7 cells. The microcapsules are easily fabricated from homochiral polymers, and the resulting architectures can be used for supramolecular chiral catalysis and many other potential applications. Enantiospecific delivery of siRNA to Huh 7 cells is seen by one 'enantiomer' of the polymers delivering siRNA with significantly improved transfection efficiency and reduced toxicity compared to the 'enantiomeric' polymer and commercially available transfection reagents. Taken together, the use of these easily accessible polyamine structures for diverse applications is highlighted in this Letter herein and can lead to numerous future research efforts.

Article	Year
Structure-based discovery of nonpeptidic small organic compounds to block the T cell response to myelin basic protein. Journal of medicinal chemistry\| PubMed ID: 15456243	2004
Human transcription factor Sp3: genomic structure, identification of a processed pseudogene, and transcript analysis. Gene\| PubMed ID: 15474306	2004
Phase I trial of sequential low-dose 5-aza-2'-deoxycytidine plus high-dose intravenous bolus interleukin-2 in patients with melanoma or renal cell carcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research\| PubMed ID: 16899610	2006
Optimal management strategy for incidental findings in trauma patients: an initiative for midlevel providers. The Journal of trauma\| PubMed ID: 18695467	2008
Elevated carbon dioxide does not offset loss of soil carbon from a corn-soybean agroecosystem. Environmental pollution (Barking, Essex : 1987)\| PubMed ID: 19631429	2010
An initiative by midlevel providers to conduct tertiary surveys at a level I trauma center. The Journal of trauma\| PubMed ID: 20453759	2010
Chiral cationic polyamines for chiral microcapsules and siRNA delivery. Bioorganic & medicinal chemistry letters\| PubMed ID: 24035095	2013

Kelly Moran

Biography

JoVE Journal Publications

Other Publications