176 research outputs found
Study of expression and role of Metabotropic Glutamate Receptors in Human Acute Myeloid Leukemia cell lines and involvement of L1-CAM in migration of mGluR1+ mouse melanoma cell lines
No full textmGluRs are a family of G-coupled protein receptors with widespread expression in the central nervous system (CNS), some normal tissues, and in various cancers. The predominant functions of mGluRs in the CNS are modulating presynaptic neurotransmission but in cancers, mGluRs are involved in regulating cell proliferation.
Acute Myeloid Leukemia (AML) is a clonal, malignant disease of hematopoietic tissue and is the most common type of acute leukemia in adults and the elderly. Despite the wide number of drugs available to treat this disease, there are many unmet needs in AML therapy; relapsed or refractory patients or those unable to receive intensive chemotherapy display a poor prognosis.
Skin cancer is described as the abnormal multiplication of skin cells, which is frequently detected in sun-exposed regions. Basal cell carcinoma, squamous cell carcinoma, Merkel cell carcinoma, cutaneous lymphoma, Kaposi sarcoma, and melanoma are the six primary forms. Melanoma is the most severe form of skin cancer and is caused by melanocyte transformation. In the United States, invasive melanoma is expected to account for about 100,000 new cases and over 7,000 fatalities from skin cancer in 2022.
In this study, there are two distinct studies, in one, we evaluated metabotropic glutamate receptors (mGluRs) to assess if one or more of mGluRs may be a putative therapeutic target in AML. We have found a novel, previously unknown role of mGluRs in AML. The second study is to use mGluR1+ mouse melanoma cell lines to determine if the presence of L1-NCAM (CD171), a neural cell adhesion molecule 1 is involved in cell migration as shown previously in glioblastoma cell
Discovery of a New Class of Potent MMP Inhibitors by Structure-Based Optimization of the Arylsulfonamide Scaffold
No full textA new class of potent matrix metalloproteinase (MMP) inhibitors designed by structure-based optimization of the well-known arylsulfonamide scaffold is presented. Molecules show an ethylene linker connecting the sulfonamide group with the P1′ aromatic portion and a d-proline residue bearing the zinc-binding group. The affinity improvement provided by these modifications led us to discover a nanomolar MMP inhibitor bearing a carboxylate moiety as zinc-binding group, which might be a promising lead molecule. Notably, a significant selectivity for MMP-8, MMP-12, and MMP-13 was observed with respect to MMP-1 and MMP-7
Phonotactic probabilities in Italian simplex and complex words: a fragment priming study.
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Revisiting paramagnetic relaxation enhancements in slowly rotating systems: how long is the long range?
No full textCross-relaxation terms in paramagnetic systems that reorient rigidly with slow tumbling times can increase the effective longitudinal relaxation rates of protons of more than 1 order of magnitude. This is evaluated by simulating the time evolution of the nuclear magnetization using a complete relaxation rate-matrix approach. The calculations show that the Solomon dependence of the paramagnetic relaxation rates on the metal–proton
distance (as r−6) can be incorrect for protons farther than 15 Å from the metal and thus can cause sizable errors in R1-derived distance restraints used, for instance, for protein structure determination. Furthermore, the chemical exchange of these protons with bulk water protons can enhance the relaxation rate of the solvent protons by far more than expected from the paramagnetic Solomon equation. Therefore, it may contribute significantly to the water proton relaxation rates measured at magnetic resonance imaging (MRI) magnetic fields in the presence of slow-rotating nanoparticles containing paramagnetic ions and a large number of exchangeable surface protons
The crystal structure of yeast copper thionein: the solution of a long-lasting enigma
No full textWe report here the crystal structure of yeast copper thionein (Cu-MT), determined at 1.44-A resolution. The Cu-MT structure shows the largest known oligonuclear Cu(I) thiolate cluster in biology, consisting of six trigonally and two digonally coordinated Cu(I) ions. This is at variance with the results from previous spectroscopic determinations, which were performed on MT samples containing seven rather than eight metal ions. The protein backbone has a random coil structure with the loops enfolding the copper cluster, which is located in a cleft where it is bound to 10 cysteine residues. The protein structure is somewhat different from that of Ag(7)-MT and similar, but not identical, to that of Cu(7)-MT. Besides the different structure of the metal cluster, the main differences lie in the cysteine topology and in the conformation of some portions of the backbone. The present structure suggests that Cu-MT, in addition to its role as a safe depository for copper ions in the cell, may play an active role in the delivery of copper to metal-free chaperones
Expression, purification, crystallization and preliminary X-ray characterization of the class B acid phosphatase (AphA) from Escherichia coli
No full textThe class B non-specific acid phosphatase AphA from Escherichia coli has been expressed in E coli and purified following a new protocol. ESI mass spectroscopy shows that the purified enzyme solution contains two polypeptides with molecular weights differing by 185 Da corresponding to two different cleavage sites of the signal peptide from the AphA E. coli precursor. Despite the solution heterogeneity, X-ray quality crystals have been obtained. However, the crystals have a tendency to give polymorphs and to lose long-range order with time while maintaining an intact crystal habit. Crystals have been grown in space groups I222 and C2 with three different unit cells and different asymmetric unit contents. Diffraction data to 1.6 Angstrom resolution have been collected with synchrotron radiation at ESRF and DESY
Ligand Binding and Structural Analysis of a Human Putative Cellular Retinol-binding Protein
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Human Ind1 expression causes over-expression of E. coli beta-lactamase ampicillin resistance protein.
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