84 research outputs found
Stereo-Selectivity of Human Serum Albumin to Enantiomeric and Isoelectronic Pollutants Dissected by Spectroscopy, Calorimetry and Bioinformatics
1–naphthol (1N), 2–naphthol (2N) and 8–quinolinol (8H) are general water pollutants. 1N and 2N are the configurational enantiomers and 8H is isoelectronic to 1N and 2N. These pollutants when ingested are transported in the blood by proteins like human serum albumin (HSA). Binding of these pollutants to HSA has been explored to elucidate the specific selectivity of molecular recognition by this multiligand binding protein. The association constants (Kb) of these pollutants to HSA were moderate (104–105 M−1). The proximity of the ligands to HSA is also revealed by their average binding distance, r, which is estimated to be in the range of 4.39–5.37 nm. The binding free energy (ΔG) in each case remains effectively the same for each site because of enthalpy–entropy compensation (EEC). The difference observed between ΔCpexp and ΔCpcalc are suggested to be caused by binding–induced flexibility changes in the HSA. Efforts are also made to elaborate the differences observed in binding isotherms obtained through multiple approaches of calorimetry, spectroscopy and bioinformatics. We suggest that difference in dissociation constants of pollutants by calorimetry, spectroscopic and computational approaches could correspond to occurrence of different set of populations of pollutants having different molecular characteristics in ground state and excited state. Furthermore, our observation of enhanced binding of pollutants (2N and 8H) in the presence of hemin signifies that ligands like hemin may enhance the storage period of these pollutants in blood that may even facilitate the ill effects of these pollutants
A Mouse Model of Acrodermatitis Enteropathica: Loss of Intestine Zinc Transporter ZIP4 (Slc39a4) Disrupts the Stem Cell Niche and Intestine Integrity
Loss-of-function of the zinc transporter ZIP4 in the mouse intestine mimics the lethal human disease acrodermatitis enteropathica. This is a rare disease in humans that is not well understood. Our studies demonstrate the paramount importance of ZIP4 in the intestine in this disease and reveal that a root cause of lethality is disruption of the intestine stem cell niche and impaired function of the small intestine. This, in turn, leads to dramatic weight loss and death unless treated with exogenous zinc
LRRK2 Biology from structure to dysfunction: research progresses, but the themes remain the same
Since the discovery of leucine-rich repeat kinase 2 (LRRK2) as a protein that is likely central to the aetiology of Parkinson's disease, a considerable amount of work has gone into uncovering its basic cellular function. This effort has led to the implication of LRRK2 in a bewildering range of cell biological processes and pathways, and probable roles in a number of seemingly unrelated medical conditions. In this review we summarise current knowledge of the basic biochemistry and cellular function of LRRK2. Topics covered include the identification of phosphorylation substrates of LRRK2 kinase activity, in particular Rab proteins, and advances in understanding the activation of LRRK2 kinase activity via dimerisation and association with membranes, especially via interaction with Rab29. We also discuss biochemical studies that shed light on the complex LRRK2 GTPase activity, evidence of roles for LRRK2 in a range of cell signalling pathways that are likely cell type specific, and studies linking LRRK2 to the cell biology of organelles. The latter includes the involvement of LRRK2 in autophagy, endocytosis, and processes at the trans-Golgi network, the endoplasmic reticulum and also key microtubule-based cellular structures. We further propose a mechanism linking LRRK2 dimerisation, GTPase function and membrane recruitment with LRRK2 kinase activation by Rab29. Together these data paint a picture of a research field that in many ways is moving forward with great momentum, but in other ways has not changed fundamentally. Many key advances have been made, but very often they seem to lead back to the same places
MEASUREMENT OF THE CRITICAL-TEMPERATURES AND CRITICAL PRESSURES OF SOME THERMALLY STABLE OR MILDLY UNSTABLE ESTERS, KETONES, AND ETHERS
MEASUREMENT OF THE CRITICAL-TEMPERATURES AND CRITICAL PRESSURES OF SOME THERMALLY STABLE OR MILDLY UNSTABLE ALKANOLS
Plasma homocysteine, apolipoprotein E status and vascular disease in elderly patients with mental illness
The relation between tissue kallikrein excretion rate, aldosterone and glomerular filtration rate in human pregnancy
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SATELLITE QUENCHING and GALACTIC CONFORMITY at 0.3 < z < 2.5
We measure the evolution of the quiescent fraction and quenching efficiency of satellites around star-forming and quiescent central galaxies with stellar mass at . We combine imaging from three deep near-infrared-selected surveys (ZFOURGE/CANDELS, Ultra Deep Survey, and UltraVISTA), which allows us to select a stellar-mass complete sample of satellites with . Satellites for both star-forming and quiescent central galaxies ("centrals") have higher quiescent fractions compared to field galaxies matched in stellar mass at all redshifts. We also observe "galactic conformity": satellites around quiescent centrals are more likely to be quenched compared to the satellites around star-forming centrals. In our sample, this conformity signal is significant at for , whereas it is only weakly significant at and . Therefore, conformity (and thus satellite quenching) has been present for a significant fraction of the age of the universe. The satellite quenching efficiency increases with increasing stellar mass of the central, but does not appear to depend on the stellar mass of the satellite to the mass limit of our sample. When we compare the satellite quenching efficiency of star-forming centrals with stellar masses 0.2 dex higher than quiescent centrals (which should account for any difference in halo mass), the conformity signal decreases, but remains statistically significant at . This is evidence that satellite quenching is connected to the star formation properties of the central galaxy as well as to the mass of the halo. We discuss physical effects that may contribute to galactic conformity, and emphasize that they must allow for continued star formation in the central galaxy even as the satellites are quenched
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