77 research outputs found
Contributions to peptidomimetic design: predictive computational studies and syntheses of linker molecules
In an effort to partially mimic the complex interaction between nerve growth
factor (NGF) and its membrane-bound tyrosine kinase A receptor (TrkA), several small
organic molecules with functionalities similar to the side-chains of the amino acid
residues of NGF critical to binding were devised. These molecules were studied
computationally using the program Affinity. Each molecule was individually docked onto
one of the binding sites on TrkA as determined by mutagenesis studies and the x-ray
crystal structure obtained from the Protein Data Bank.
One of the strategies to enhance binding of active peptidomimetics to their target
proteins is to link them together to form either homodimers or heterodimers. However,
these dimers have low solubility in water and mimic only residues that are close together
on the protein. Triethylene oxide- and hexaethylene oxide-based linker molecules were
designed to circumvent these limitations. The increased polarity will improve the watersolubility
and the added lengths, which can be controlled and varied by simple chemical
manipulations, will allow for mimicking critical residues that are farther apart on the
protein
Isolation of a Glucosamine Binding Leguminous Lectin with Mitogenic Activity towards Splenocytes and Anti-Proliferative Activity towards Tumor Cells
A dimeric 64-kDa glucosamine-specific lectin was purified from seeds of Phaseolus vulgaris cv. “brown kidney bean.” The simple 2-step purification protocol involved affinity chromatography on Affi-gel blue gel and gel filtration by FPLC on Superdex 75. The lectin was absorbed on Affi-gel blue gel and desorbed using 1M NaCl in the starting buffer. Gel filtration on Superdex 75 yielded a major absorbance peak that gave a single 32-kDa band in SDS-PAGE. Hemagglutinating activity was completely preserved when the ambient temperature was in the range of 20°C–60°C. However, drastic reduction of the activity occurred at temperatures above 65°C. Full hemagglutinating activity of the lectin was observed at an ambient pH of 3 to 12. About 50% activity remained at pH 0–2, and only residual activity was observed at pH 13–14. Hemagglutinating activity of the lectin was inhibited by glucosamine. The brown kidney bean lectin elicited maximum mitogenic activity toward murine splenocytes at 2.5 µM. The mitogenic activity was nearly completely eliminated in the presence of 250 mM glucosamine. The lectin also increased mRNA expression of the cytokines IL-2, TNF-α and IFN-γ. The lectin exhibited antiproliferative activity toward human breast cancer (MCF7) cells, hepatoma (HepG2) cells and nasopharyngeal carcinoma (CNE1 and CNE2) cells with IC50 of 5.12 µM, 32.85 µM, 3.12 µM and 40.12 µM respectively after treatment for 24 hours. Flow cytometry with Annexin V and propidum iodide staining indicated apoptosis of MCF7 cells. Hoechst 33342 staining also indicated formation of apoptotic bodies in MCF7 cells after exposure to brown kidney bean lectin. Western blotting revealed that the lectin-induced apoptosis involved ER stress and unfolded protein response
Genetic Associations of Type 2 Diabetes with Islet Amyloid Polypeptide Processing and Degrading Pathways in Asian Populations
10.1371/journal.pone.0062378PLoS ONE86
The Science Performance of JWST as Characterized in Commissioning
This paper characterizes the actual science performance of the James Webb
Space Telescope (JWST), as determined from the six month commissioning period.
We summarize the performance of the spacecraft, telescope, science instruments,
and ground system, with an emphasis on differences from pre-launch
expectations. Commissioning has made clear that JWST is fully capable of
achieving the discoveries for which it was built. Moreover, almost across the
board, the science performance of JWST is better than expected; in most cases,
JWST will go deeper faster than expected. The telescope and instrument suite
have demonstrated the sensitivity, stability, image quality, and spectral range
that are necessary to transform our understanding of the cosmos through
observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures;
https://iopscience.iop.org/article/10.1088/1538-3873/acb29
The James Webb Space Telescope Mission
Twenty-six years ago a small committee report, building on earlier studies,
expounded a compelling and poetic vision for the future of astronomy, calling
for an infrared-optimized space telescope with an aperture of at least .
With the support of their governments in the US, Europe, and Canada, 20,000
people realized that vision as the James Webb Space Telescope. A
generation of astronomers will celebrate their accomplishments for the life of
the mission, potentially as long as 20 years, and beyond. This report and the
scientific discoveries that follow are extended thank-you notes to the 20,000
team members. The telescope is working perfectly, with much better image
quality than expected. In this and accompanying papers, we give a brief
history, describe the observatory, outline its objectives and current observing
program, and discuss the inventions and people who made it possible. We cite
detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space
Telescope Overview, 29 pages, 4 figure
Does shoe heel design influence ground reaction forces and knee moments during maximum lunges in elite and intermediate badminton players?
Supplier Selection Problem with Type-2 Fuzzy Parameters: A Neutrosophic Optimization Approach
Purification and Characterization of a Glucosamine-Binding Antifungal Lectin from Phaseolus vulgaris cv. Chinese Pinto Beans with Antiproliferative Activity Towards Nasopharyngeal Carcinoma Cells
A novel 2D silicon nano-mold fabrication technique for linear nanochannels over a 4 inch diameter substrate
Protection of the Transplant Kidney from Preservation Injury by Inhibition of Matrix Metalloproteinases
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