Can iron depletion inside macrophages serve to prolong HIV disease progression?

Studies have shown that the more iron in a given population, the more that population is vulnerable to intracellular opportunistic infections (OIs) in AIDS, mainly because these microbes make use of the intracellular iron to proliferate, and could render infections deadly. In contrast, macrophages that lack iron are effective in preventing an establishment of infection. We propose that reduction in total body iron could be a valuable treatment option for some intracellular infections, including OIs. We suggest two options to deprive pathogens of using intracellular iron (i) to practice regular blood-letting, an ancient treatment option, and (ii) to down-regulate hepcidin, the key hormone involved in the regulation of iron balance and recycling. This could also deprive transformed cells of metabolizing iron for survival. Whether or these methods serve to curb the onset of OIs/cancers to prolong HIV disease progression remains to be investigated.     

An InCytes from MBC Selection: Membrane Insertion of the Pleckstrin Homology Domain Variable Loop 1 Is Critical for Dynamin-catalyzed Vesicle Scission

The GTPase dynamin catalyzes the scission of deeply invaginated clathrin-coated pits at the plasma membrane, but the mechanisms governing dynamin-mediated membrane fission remain poorly understood. Through mutagenesis, we have altered the hydrophobic nature of the membrane-inserting variable loop 1 (VL1) of the pleckstrin homology (PH) domain of dynamin-1 and demonstrate that its stable insertion into the lipid bilayer is critical for high membrane curvature generation and subsequent membrane fission. Dynamin PH domain mutants defective in curvature generation regain function when assayed on precurved membrane templates in vitro, but they remain defective in the scission of clathrin-coated pits in vivo. These results demonstrate that, in concert with dynamin self-assembly, PH domain membrane insertion is essential for fission and vesicle release in vitro and for clathrin-mediated endocytosis in vivo.     

Cooperative binding between distant transcription factors is a hallmark of active enhancers

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The role of extracellular calcium in corticotropin-stimulated steroidogenesis

The role of extracellular Ca2+ in the binding of corticotropin (ACTH) to adrenocortical cell receptors as well as in the post-binding events involved in steroidogenesis were investigated. Binding studies using [125I-Tyr23,Phe2,Nle4]ACTH (1-38) peptide showed that extracellular Ca2+ is essential not only for the interaction of ACTH with its receptor, but also for continued occupancy of the receptor. In view of the requirement of Ca2+ for binding the hormone to the receptor, the role of Ca2+ in post-receptor events was investigated by covalently attaching the hormone to its receptor by photoaffinity labeling in the presence of Ca2+. Persistent activation of steroidogenesis induced by photoaffinity labeling in the presence of Ca2+ was depressed when cells were incubated in medium containing EGTA but was unaffected when the cells were merely washed and incubated in Ca2+-free medium. In the presence of EGTA, 8-Br-cAMP partially restored persistent activation of steroidogenesis. The concentration of extracellular Ca2+ required for restoring steroidogenesis was 10-fold lower than the concentration of Ca2+ needed for optimal binding of ACTH to its receptor. These results suggest that the primary role of extracellular Ca2+ in the action of ACTH is to facilitate the association of the hormone with its receptor.     

Feeding site selection of first-instar larvae of Cnaphalocrocis medinalis on susceptible and resistant rice plants

More first-instar larvae of the rice leaffolder, Cnaphalocrocis medinalis (Guenée), were recovered from susceptible IR36 and Roxoro rice varieties than resistant TKM6 and Oryza perennis, 24 h after infestation. Within a rice plant, a higher proportion of larvae was recovered from young whorl leaf, followed by mature leaves and leafsheaths on all the four rice varieties tested. However, differences were observed between susceptible and resistant varieties in the distribution of larvae on these three plant parts. In laboratory choice tests, first-instar larvae preferred to settle on the young leaves of IR36 and TKM6 when presented with their respective mature leaves. No such preference was observed in tests with Rexoro and O. perennis. Larval survival was similar on young and mature leaves of Rexoro. Young leaves of IR36 and TKM6 were more suitable for survival in comparison with their respective mature leaves while the reverse was true for O. perennis. Larval movement was slower on the mature leaves and larvae took longer to reach the whorl leaf of TKM6 than on IR36. The density of trichomes of the abaxial surface of TKM6 was higher than that of the other varieties tested. Adaptive significance of feeding in the leafwhorl to young larvae is discussed.     

Organization of lymphoid tissue in the tonsilla lingualis

Summary Lymphoid organs are highly organized structures made up of different tissue compartments, each with its own specific cell populations. However, the cellular elements of the lingual tonsil, which forms a significant part of Waldeyer's pharyngeal ring, are not yet documented. This study, therefore, describes the fine structure and tissue organization of tonsilla lingualis in Macaca fascicularis. Ten selected crypto-lymphatic units originating from five perfusion-fixed animals were analysed ultrastructurally. Based on the fine-structural elements contained within, the lymphoid tissue of tonsillar units could be subdivided into follicular (germinal centre) and parafollicular areas. The latter contained predominantly small lymphocytes, lymphoblasts resembling T-blasts, plasma cells, macrophages, occasional neutrophils and many reticular cells resembling fibroblasts. A distinct feature of the parafollicular area was the presence of numerous high endothelial (HEV)or postcapillary venules (PCV). The follicular areas contained many small and large lymphoid cells, mitotic cells, plasmablasts, macrophages and specialised reticular cells resembling follicular dendritic cells (FDC) with distinct desmosomal junctions. These observations show that the crypto-lymphatic units of the lingual tonsil are, in fact, organised into distinct B- and T-cell compartments with their own specific lymphoid and accessory cells.     

Oxidatively Induced Structural Alteration of Glutamine Synthetase Assessed by Analysis of Spin Label Incorporation Kinetics: Relevance to Alzheimer's Disease

Abstract: The activity of the astrocytic enzyme glutamine synthetase (GS) is decreased in the Alzheimer's disease brain, which may have relevance to mechanisms of chronic excitotoxicity. The molecular perturbation(s) that results in GS inactivation is not known, although oxidative lesioning of the enzyme is one likely cause. To assess structural perturbation induced in GS by metal-catalyzed oxidation, a series of spin-labeling studies were undertaken. Ovine GS was oxidized by exposure to iron/hydrogen peroxide and subsequently labeled with the thiol-specific nitroxide probe MTS [(1-oxyl-2,2,5,5-tetramethyl-pyrroline-3-methyl)methanethiosulfonate]. The reaction of MTS with cysteine residues within GS was monitored in real time by electron paramagnetic resonance spectrometry. Structural perturbation of GS, manifested as decreased thiol accessibility, was inferred from an apparent decrease in the rate constant for the second-order reaction of MTS with protein thiols. A subsequent spin-labeling study was undertaken to compare the structural integrity of GS purified and isolated from Alzheimer's disease-afflicted brain (AD-GS) with that of GS isolated from nondemented, age-matched control brain (C-GS). The rate constant for reaction of MTS with AD-GS was markedly decreased relative to that for the reaction of spin label with C-GS. The kinetic data were partially corroborated by spectroscopic data obtained from circular dichroism analysis of control and peroxide-treated ovine GS. In an adjunct experiment, the interaction of GS with a synthetic analogue of the Alzheimer's-associated β-amyloid peptide, known to induce free radical oxidative stress, indicated strong interaction of the enzyme with the peptide as reflected by a decrease in the rate constant for MTS binding to reactive protein thiols.