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Human cytomegalovirus-induced host cell enlargement is iron dependent. Am J Physiol Cell Physiol 287: C1023-C1030, 2004. First published June 2, 2004; 10.1152/ajpcell.00511.2003.--A hallmark of human cytomegalovirus (HCMV) infection is the characteristic enlargement of the host cells (i.e., cytomegaly). Because iron (Fe) is required for cell growth and Fe chelators inhibit viral replication, we investigated the effects of HCMV infection on Fe homeostasis in MRC-5 fibroblasts. Using the metallosensitive fluorophore calcein and the Fe chelator salicylaldehyde isonicotinoyl hydrazone (SIH), the labile iron pool (LIP) in mock-infected cells was determined to be 1.04 [+ or -] 0.05 /[micro]M. Twenty-four hours postinfection (hpi), the size of the LIP had nearly doubled. Because cytomegaly occurs between 24 and 96 hpi, access to this larger LIP could be expected to facilitate enlargement to ~375% of the initial cell size. The ability of Fe chelation by 100 [micro]M SIH to limit enlargement to ~180% confirms that the LIP plays a major role in cytomegaly. The effect of SIH chelation on the mitochondrial membrane potential ([DELTA][[PSI].sub.M]]) and morphology was studied using the mitochondrial voltage-sensitive dye JC-1. The mitochondria in mock-infected cells were heterogeneous with a broad distribution of [DELTA][[PSI].sub.M]] and were threadlike. In contrast, the mitochondria of HCMV-infected cells had a more depolarized [DELTA][[PSI].sub.M]] distributed over a narrow range and were grainlike in appearance. However. the HCMV-induced alteration in [DELTA][[PSI].sub.M]] was not affected by SIH chelation. We conclude that the development of cytomegaly is inhibited by Fe chelation and may be facilitated by an HCMV-induced increase in the LIP. cell size: mitochondria

Perinuclear localization of Na-K-Cl-cotransporter protein after human cytomegalovirus infection. Am J Physiol Cell Physiol 286:C1324-C1334, 2004. First published January 28, 2004; 10.1152/ajpcell. 00404.2003.--We (41) previously reported that Na-K-Cl-cotransporter (NKCC) function and microsomal protein expression are both dramatically reduced late in human cytomegalovirus (HCMV) infection of a human fibroblast cell line (MRC-5). We now report DNA microarray data showing that no significant HCMV-dependent NKCC gene repression can be detected 30 h postexposure (PE) to the virus. Consequently, we used plasma membrane biotinylation and subsequent subcellular fractionation in combination with semiquantitative immunoblotting and confocal microscopy to investigate the possibility that intracellular redistribution of the NKCC protein after HCMV infection could be a cause of the HCMV-induced loss of NKCC ion transport function. Our results show that the lifetime of plasmalemmal NKCC protein in quiescent, uninfected MRC-5 cells is ~48 h, and sodium-potassium-chloride-cotransporter; human fibroblast cell line; perinuclear accumulation

Research was conducted to investigate whether human cytomegalovirus (HCMV) infection increased Cl-/HCO3- exchanger activity over the same time period it enhances Na+/H+ exchanger (NHE) activity in human lung fibroblasts. The study was performed using fluorescent, ion-sensitive dyes. Results demonstrate that HCMV infection causes a substantial enhancement of Cl-/HCO3- exchanger activity.

The underlying mechanism leading to the enlargement of host cells attacked by human cytomegalovirus (HCMV) were investigated based on the proposition that cell volume increase is osmotically driven. Experimental observations supported the view that an association exists between cytomegaly and alterations of sodium ion transport mechanisms. Moreover, it has also been observed that reduction of sodium ion in culture medium after HCMV infection inhibits the development of cytomegaly.

Substrate-controlled diastereoselective reactions with (R)-pulegone have been used to synthesize the naturally-occurring diterpene (+)-epoxydictymene. Dicobalt hexacarbonyl complexes of alkynes were used in Lewis acid-promoted Nicholas and Pauson-Khand intramolecular reaction to form three octane ring systems: alpha-funebrene, pardalianchol and alpha-8-hydroxypresilphiperfolene.

A facile synthetic route utilizing readily available reagents is used in a study to develop a series of regiosomerically pure xanthene dye derivatives. Advantages of the method include relatively mild conditions and good to excellent yields.

Computational studies on the mechanism and diastereoselectivity of base catalyzed synthesis of bicyclo[3.3.1]nonanes by are reported. Three possible mechanisms were considered, and only the methanol assisted H-shift process could be the favorable pathway. We have discovered a rare Curtin-Hammet scenario: rate determining steps for the two diastereomeric products formed are completely different reactions, and a correction factor should be considered when gauging the ratio of products from competing pathways. The pathway leading to the anti product is kinetically preferred, which is consistent with experimental results. Finally, the ratio of the two products was rationalized. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Butyrolactone synthesis was undertaken using catalytic asymmetric cyclocarbonylation.

The insertion of an isonitrile into metal-alkyl bond for d-block, actinide, and lanthanide elements activates the cyclopentadienyl ligand in titanocene complexes. One of the ligand adopts a lower hapticity binding mode during the reaction between titanocene and t-BuNC, which results in a complex having one cyclopentadienyl ligand possessing five unequivalent hydrogens and carbons according to 1H- and 13C-NMR. The above reaction demonstrates the labile nature of the otherwise stable cyclopentadienyl ligand.

A titanium-mediated synthesis of gamma-butyrolactones can be performed through the reaction sequence of reductive coupling-carbonylation-reductive elimination. Advantages of this new process include the mild reaction conditions required and the readily available titanium reagent. The process has been successfully employed in the intramolecular coupling of aldehydes or ketones to terminal olefins.

The titanium-catalyzed carbonyl-olefin and carbonyl-alkyne reductive cyclization reactions result in the formation of a metallacyclopentane with concomitant formation of a carbon-carbon bond because both ketones and aldehydes are good substrates for the titanium-catalyzed reductive cyclization reactions. The cis selectivity of the carbon-carbon bond forming reaction is complimentary to the trans selectivity obtained in related samarium-mediated cyclizations.

Cross-metathesis of a productive olefin, acrylonitrile, with a more nucleophilic olefin in the presence of Schrock's molybdenum catalyst revealed complete conversion and high yields in dichloromethane, but not in pentane or toluene. It is suggested that substrate type determines reaction efficiency, with alkyl-substituted olefins with electron-withdrawing substituents giving rise to low yield and selectivity. The proposed mechanism of the metathesis reactivity is discussed.

Alkyne-dicobalt hexacarbonyl complexes are employed for the stereoselective total synthesis of (+)-epoxydictymene. The technique yields the (R)-pulegone asymmetry and does not use protecting groups. A trans-fused 5-5 ring system is constructed via an anionic intramolecular cyclization. This is the first total synthesis of a natural product containing a trans-fused 5-5 ring system.

Research was conducted to examine the effects of human cytomegalovirus (HCMV) infection on the Na+-K+-Cl- cotransporter (NKCC) in a human fibroblast cell line. It was observed through the use of the Cl-sensitive dye MQAE, that the mock-infected MRC-5 cells express a functional NKCC. Results indicate that HCMV infection leads to the abolition of NKCC function coincident with the severe reduction in the amount of NKCC protein expressed.