Beryllium is an inhibitor of cellular GSK-3β that is 1,000-fold more potent than lithium

Glycogen synthase kinase 3β (GSK-3β) is a key regulator in signaling networks that control cell proliferation, metabolism, development, and other processes. Lithium chloride is a GSK-3 family inhibitor that has been a mainstay of in vitro and in vivo studies for many years. Beryllium salt has the potential to act as a lithium-like inhibitor of GSK-3, but it is not known whether this agent is effective under physiologically relevant conditions. Here we show that BeSO₄ inhibits endogenous GSK-3β in cultured human cells. Exposure to 10 µM Be²⁺ produced a decrease in GSK-3β kinase activity that was comparable to that produced by 10 mM Li⁺, indicating that beryllium is about 1,000-fold more potent than the classical inhibitor when treating intact cells. There was a statistically significant dose-dependent reduction in specific activity of GSK-3β immunoprecipitated from cells that had been treated with either agent. Lithium inhibited GSK-3β kinase activity directly, and it also caused GSK-3β in cells to become phosphorylated at serine-9 (Ser-9), a post-translational modification that occurs as part of a well-known positive feedback loop that suppresses the kinase activity. Beryllium also inhibited the kinase directly, but unlike lithium it had little effect on Ser-9 phosphorylation in the cell types tested, suggesting that alternative modes of feedback inhibition may be elicited by this agent. These results indicate that beryllium, like lithium, can induce perturbations in the GSK-3β signaling network of treated cells.     

Hexavalent Chromium Reduction from Pollutant Samples by <Emphasis Type="Italic">Achromobacter xylosoxidans</Emphasis> SHB 204 and its Kinetics Study

Cr(VI) is most toxic heavy metal and second most widespread hazardous metal compound worldwide. Present work focused on Cr(VI) reduction from synthetic solutions and polluted samples by Achromobacter xylosoxidans SHB 204. It could tolerate Cr(VI) up to 1600 ppm and reduce 500 ppm with 4.5 chromium reductase enzyme units (U) having protein size 30 kDa. Changes in morphology of cells on interaction with Cr(VI) metal ion was also studied using SEM–EDX and FTIR. Microcosm studies in pollutant samples for Cr(VI) reduction and adsorption isotherm with biomass of bacterium was best fitted with Langmuir model along with kinetic studies. This study focuses on significance of Cr reduction from synthetic solutions and polluted samples by A. xylosoxidans SHB 204 and its potential for bioremediation.     

Multiple helical conformations of the helix‐turn‐helix region revealed by NOE‐restrained MD simulations of tryptophan aporepressor,TrpR

The nature of flexibility in the helix‐turn‐helix region of E. coli trp aporepressor has been unexplained for many years. The original ensemble of nuclear magnetic resonance (NMR structures showed apparent disorder, but chemical shift and relaxation measurements indicated a helical region. Nuclear Overhauser effect (NOE) data for a temperature‐sensitive mutant showed more helical character in its helix‐turn‐helix region, but nevertheless also led to an apparently disordered ensemble. However, conventional NMR structure determination methods require all structures in the ensemble to be consistent with every NOE simultaneously. This work uses an alternative approach in which some structures of the ensemble are allowed to violate some NOEs to permit modeling of multiple conformational states that are in dynamic equilibrium. Newly measured NOE data for wild‐type aporepressor are used as time‐averaged distance restraints in molecular dynamics simulations to generate an ensemble of helical conformations that is more consistent with the observed NMR data than the apparent disorder in the previously reported NMR structures. The results indicate the presence of alternating helical conformations that provide a better explanation for the flexibility of the helix‐turn‐helix region of trp aporepressor. Structures representing these conformations have been deposited with PDB ID: 5TM0. Proteins 2017; 85:731–740. © 2016 Wiley Periodicals, Inc.     

Autophagy enhancement is rendered ineffective in presence of α-synuclein in melanoma cells

Increased cellular concentration of α-synuclein (α-syn) predisposes it to misfolding and aggregation that in turn impair the degradation pathways. This poses a limitation to the use of overexpression models for studies on α-syn clearance by autophagy, which is widely investigated for its therapeutic potential. This limitation can be overcome with the use of endogenous models. In this study, SK-MEL-28, a melanoma cell model with endogenous α-syn expression, was employed to study α-syn clearance through autophagy. We demonstrated the dual localization of α-syn to nucleus and cytoplasm that varied in response to changes in cellular environment. Autophagy inhibition and exposure to dopamine favored cytoplasmic localization of α-syn, while autophagy induction favored increased localization to the nucleus. The inhibitory effect of dopamine on autophagy was heightened in presence of α-syn. Additionally, because α-syn had a regulatory effect on autophagy, cells showed an increased resistance to autophagy induction in presence of α-syn. This resistance prevented effective induction of autophagy even under conditions of prolonged autophagy inhibition. These results highlight alternate physiological roles of α-syn, particularly in non-neuronal cells. Because autophagy enhancement could reverse neither the increase in α-syn levels nor the autophagy inhibition, there arises a need to evaluate the efficacy of autophagy-based therapeutic strategies.     

Coelonin,A 9,10-dihydrophenanthrene from the orchids Coelogyne ochracea and Coelogyne elata

2,7-Dihydroxy-4-methoxy-9,10-dihydrophenanthrene was isolated and identified from the whole plant of Coelogyne ochracea and C. elata.     

Airborne pollen survey of central calcutta,india, in relation to allergy

A continuous aeropalynological survey at Central Calcutta for two consecutive years (1985–1987) was done by using a Burkard Seven Day Recording Volumetric Spore Trap. A total of 65 pollen taxa was identified of which pollen of Trema orientalis showed a maximum frequency (about 68%) followed by Poaceae and Cyperaceae. A pollen calendar was prepared and seasonal periodicities were recorded. Some entomophilous pollen types (e.g., Delonix regia, Bougainvillea spectabilis) were also observed. The presence of pollen of Pinus, Podocarpus, and Alnus in the air of Calcutta is probably due to long distance transport from Eastern Himalayas where these plants grow. Routine skin tests were performed by using the antigenic extracts of 22 pollen types where grass, Catharanthus roseus, Cocos nucifera, Azadirachta indica, Carica papaya, Albizia lebbek, Shorea robusta, Eucalyptus sp., Terminalia sp., were proved to be allergenically potent.