UDP-glucose 4, 6-dehydratase Activity Plays an Important Role in Maintaining Cell Wall Integrity and Virulence of Candida albicans

Candida albicans, a human fungal pathogen, undergoes morphogenetic changes that are associated with virulence. We report here that GAL102 in C. albicans encodes a homolog of dTDP-glucose 4,6-dehydratase, an enzyme that affects cell wall properties as well as virulence of many pathogenic bacteria. We found that GAL102 deletion leads to greater sensitivity to antifungal drugs and cell wall destabilizing agents like Calcofluor white and Congo red. The mutant also formed biofilms consisting mainly of hyphal cells that show less turgor. The NMR analysis of cell wall mannans of gal102 deletion strain revealed that a major constituent of mannan is missing and the phosphomannan component known to affect virulence is greatly reduced. We also observed that there was a substantial reduction in the expression of genes involved in biofilm formation but increase in the expression of genes encoding glycosylphosphatidylinositol-anchored proteins in the mutant. These, along with altered mannosylation of cell wall proteins together might be responsible for multiple phenotypes displayed by the mutant. Finally, the mutant was unable to grow in the presence of resident peritoneal macrophages and elicited a weak pro-inflammatory cytokine response in vitro. Similarly, this mutant elicited a poor serum pro-inflammatory cytokine response as judged by IFN gamma and TNF alpha levels and showed reduced virulence in a mouse model of systemic candidiasis. Importantly, an Ala substitution for a conserved Lys residue in the active site motif YXXXK, that abrogates the enzyme activity also showed reduced virulence and increased filamentation similar to the gal102 deletion strain. Since inactivating the enzyme encoded by GAL102 makes the cells sensitive to antifungal drugs and reduces its virulence, it can serve as a potential drug target in combination therapies for C. albicans and related pathogens.

A power scalable receiver front-end at 2.4 GHz

We propose a Low Noise Amplifier (LNA) architecture for power scalable receiver front end (FE) for Zigbee. The motivation for power scalable receiver is to enable minimum power operation while meeting the run-time performance needed. We use simple models to find empirical relations between the available signal and interference levels to come up with required Noise Figure (NF) and 3rd order Intermodulation Product (IIP3) numbers. The architecture has two independent digital knobs to control the NF and IIP3. Acceptable input match while using adaptation has been achieved by using an Active Inductor configuration for the source degeneration inductor of the LNA. The low IF receiver front end (LNA with I and Q mixers) was fabricated in 130nm RFCMOS process and tested.

Maximum rate of 3- and 4-real-symbol ML decodable unitary weight STBCs

It has been shown recently that the maximum rate of a 2-real-symbol (single-complex-symbol) maximum likelihood (ML) decodable, square space-time block codes (STBCs) with unitary weight matrices is 2a/2a complex symbols per channel use (cspcu) for 2a number of transmit antennas [1]. These STBCs are obtained from Unitary Weight Designs (UWDs). In this paper, we show that the maximum rates for 3- and 4-real-symbol (2-complex-symbol) ML decodable square STBCs from UWDs, for 2a transmit antennas, are 3(a-1)/2a and 4(a-1)/2a cspcu, respectively. STBCs achieving this maximum rate are constructed. A set of sufficient conditions on the signal set, required for these codes to achieve full-diversity are derived along with expressions for their coding gain.

l-pGlu-(2-propyl)-l-His-l-ProNH2 attenuates 4-aminopyridine-induced epileptiform activity and sodium current: a possible action of new thyrotropin-releasing hormone analog for its anticonvulsant potential

L-PGlu-(2-proPyl)-L-His-L-ProNH(2) (NP-647) is a CNS active thyrotropin-releasing hormone (TRH) analog with potential application in various CNS disorders including seizures. In the present study, mechanism of action for protective effect of NP-647 was explored by studying role of NP-647 on epileptiform activity and sodium channels by using patch-clamp methods. Epileptiform activity was induced in subicular pyramidal neurons of hippocampal slice of rat by perfusing 4-aminopyridine (4-AP) containing Mg(+2)-free normal artificial cerebrospinal fluid (nACSF). Increase in mean firing frequency was observed after perfusion of 4-AP and zero Mg(+2) (2.10+/-0.47 Hz) as compared with nACSF (0.12+/-0.08 Hz). A significant decrease in mean firing frequency (0.61+/-0.22 Hz), mean frequency of epileptiform events (0.03+/-0.02 Hz vs. 0.22+/-0.05 Hz of 4-AP+0 Mg), and average number of action potentials in paroxysmal depolarization shift-burst (2.54+/-1.21 Hz vs. 8.16+/-0.88 Hz of 4-AP +0 Mg) was observed. A significant reduction in peak dV/dt (246+/-19 mV ms(-1) vs. 297 18 mV ms-1 of 4-AP+0 Mg) and increase (1.332+/-0.018 ms vs. 1.292+/-0.019 ms of 4-AP+0 Mg) in time required to reach maximum depolarization were observed indicating role of sodium channels. Concentration-dependent depression of sodium current was observed after exposure to dorsal root ganglion neurons to NP-647. NP-647 at different concentrations (1, 3, and 10 mu M) depressed sodium current (15+/-0.5%, 50+/-2.6%, and 75+/-0.7%, respectively). However, NP-647 did not show change in the peak sodium current in CNa18 cells. Results of present study demonstrated potential of NP-647 in the inhibition of epileptiform activity by inhibiting sodium channels indirectly. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.