964 research outputs found
KIR2DL2/2DL3-E(35) alleles are functionally stronger than -Q(35) alleles.
KIR2DL2 and KIR2DL3 segregate as alleles of a single locus in the centromeric motif of the killer cell immunoglobulin-like receptor (KIR) gene family. Although KIR2DL2/L3 polymorphism is known to be associated with many human diseases and is an important factor for donor selection in allogeneic hematopoietic stem cell transplantation, the molecular determinant of functional diversity among various alleles is unclear. In this study we found that KIR2DL2/L3 with glutamic acid at position 35 (E(35)) are functionally stronger than those with glutamine at the same position (Q(35)). Cytotoxicity assay showed that NK cells from HLA-C1 positive donors with KIR2DL2/L3-E(35) could kill more target cells lacking their ligands than NK cells with the weaker -Q(35) alleles, indicating better licensing of KIR2DL2/L3(+) NK cells with the stronger alleles. Molecular modeling analysis reveals that the glutamic acid, which is negatively charged, interacts with positively charged histidine located at position 55, thereby stabilizing KIR2DL2/L3 dimer and reducing entropy loss when KIR2DL2/3 binds to HLA-C ligand. The results of this study will be important for future studies of KIR2DL2/L3-associated diseases as well as for donor selection in allogeneic stem cell transplantation
Variable Nanoparticle-Cell Adhesion Strength Regulates Cellular Uptake
In receptor-mediated endocytosis, cells exercise biochemical control over the mechanics of adhesion to engulf foreign particles, featuring a variable adhesion strength. Here we present a thermodynamic model with which we elucidate that the variable adhesion strength critically governs the cellular uptake, yielding an uptake phase diagram in the space of ligand density and particle size. We identify from the diagram an endocytosed phase with markedly high uptake, encompassed by a lower and an upper phase boundary that are set, respectively, by the enthalpic and entropic limits of the adhesion strength. The phase diagram may provide useful guidance to the rational design of nanoparticle-based therapeutic and diagnostic agents
Structure-based Discovery of Novel Small Molecule Wnt Signaling Inhibitors by Targeting the Cysteine-rich Domain of Frizzled.
Frizzled is the earliest discovered glycosylated Wnt protein receptor and is critical for the initiation of Wnt signaling. Antagonizing Frizzled is effective in inhibiting the growth of multiple tumor types. The extracellular N terminus of Frizzled contains a conserved cysteine-rich domain that directly interacts with Wnt ligands. Structure-based virtual screening and cell-based assays were used to identify five small molecules that can inhibit canonical Wnt signaling and have low IC50 values in the micromolar range. NMR experiments confirmed that these compounds specifically bind to the Wnt binding site on the Frizzled8 cysteine-rich domain with submicromolar dissociation constants. Our study confirms the feasibility of targeting the Frizzled cysteine-rich domain as an effective way of regulating canonical Wnt signaling. These small molecules can be further optimized into more potent therapeutic agents for regulating abnormal Wnt signaling by targeting Frizzled
Bis{1-[(E)-o-tolyldiazenyl]-2-naphtholato}copper(II)
In the title complex, [Cu(C17H13N2O)2], the CuII atom is tetracoordinated by two N atoms and two O atoms from two bidentate 1-[(E)-o-tolyldiazenyl]-2-naphtholate ligands, forming a slightly distorted square-planar environment. The two N atoms and two O atoms around the CuII atom are trans to each other, with an O—Cu—O bond angle of 177.00 (9)° and an N—Cu—N bond angle of 165.63 (10)°. The average distances between the CuII atom and the coordinated O and N atoms are 1.905 (2) and 1.995 (2)Å, respectively
Spectrum of the S-wave fully-heavy tetraquark states
In present work, spectrum of the -wave fully-heavy tetraquark states
(), i.e., , ,
/, / ,
/, and are
systematically investigated within an nonrelativistic constituent quark model,
in which the Instanton-induced and one-gluon-exchange interactions are taken
into account as the residual spin-dependent hyperfine interaction. Our results
show that the states with and components
could be located around MeV and MeV, respectively. Based on
our calculations, the new state observed by LHCb may be not a ground
tetraquark state, while it could be an orbitally or radially
excited state of system. On the other hand, the recently
reported state by CMS and ATLAS can be explained as a ground
tetraquark state with spin-parity .Comment: Version to appear in Eur. Phys. J.
Anti-hyperuricemic effect of Plantago depressa Willd extract in rats
Purpose: To investigate the effects of Plantago depressa Willd. extract (PDWE) on hyperuricemia in rats.Methods: The effect of PDWE was investigated in hyperuricemic rats induced by potassium oxonate. PDWE were fed to hyperuricemic rats daily at a dose of 160, 320 and 640 mg/kg for 10 days; allopurinol (5 mg/kg) was given as positive control. Serum and urine levels of uric acid and creatinine were determined by colorimetric method.Results: PDWE inhibited xanthine oxidase (XOD) activity in serum (16.36 ± 1.16 U/L, p < 0.05) and liver (72.15 ± 5.26 U/g protein, p < 0.05), and also decreased levels of serum uric acid (2.43 ± 0.59 mg/L, p < 0.05), serum creatinine (0.42 ± 0.15 μmol/L) and blood urea nitrogen (BUN, 9.58 ± 0.72 mmol/L, p < 0.05), but increased levels of urine uric acid (39.23 ± 8.22 mg/L, p < 0.05) and urine creatinine (32.24 ± 1.69 mmol/L, p < 0.05) in the renal tissue of hyperuricemic rats.Conclusion: PDWE exerts uricosuric action by regulating renal urate transporters to ameliorate renal dysfunction in hyperuricemic rats.Keywords: Plantago depressa Willd., Hyperuricemic, Renal urate transporters, Renal dysfunction, Uricosuric actio
Microwave assisted synthesis, antifungal activity, DFT and SAR study of 1,2,4-triazolo[4,3-a]pyridine derivatives containing hydrazone moieties
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