Pyrrole‐coupled salicylimine‐based fluorescence “turn on” probe for highly selective recognition of Zn2+ ions in mixed aqueous media: Application in living cell imaging

Cation sensing behaviour of a pyrrole‐based derivative (2‐hydroxyl 3 methyl 6 isopropyl benzaldehyde}‐3,4‐dimethyl‐1H‐pyrrole‐2‐carbohydrazide (receptor 3) has been explored and is found to be selective towards Zn²⁺ over a variety of tested cations. The receptor 3 has shown high selectivity and sensitivity towards Zn²⁺ over the other alkali, alkaline earth and transition metal ions. In the presence of Zn²⁺, absorption band of receptor 3 has shown the red shift. The sensing behaviour has been suggested to continue via enhancement process which has further been supported by UV‐vis absorption and theoretical density functional theory (DFT) calculations indicating the formation of a 1:1 complex between the pyrrole based receptor 3 and Zn²⁺. The present work is presenting a highly selective dual channel colorimetric sensor for zinc with great sensitivity. The developed sensor was successfully applied to image intracellular Zn²⁺ in living cells. Copyright © 2015 John Wiley & Sons, Ltd.     

X-ray diffraction study of the zinc(II) binding sites in yeast phenylalanine transfer RNA preferential binding of zinc to guanines in purine-purine sequences

An X-ray diffraction study of a zinc(II) complex of tRNA^Phe from yeast reveals the presence of five zin-binding sites on the tRNA molecule. Two of the cooperatively bound Mg²⁺ in the native tRNA structure are replaced by Zn²⁺. The remaining sites involve direct coordination of zinc to the N7 position of tRNA guanine bases, G15, G43 and G45. Thus, zinc displays a high specificity for binding to guanine bases in purine-purine sequences.     

Effect of excess water in an oxisol on ammonium,nitrate, iron and manganese availability and nutrient uptake of two tropical forage species

Summary A glasshouse experiment was conducted to determine how reduction conditions would affect plant nutrient availability and uptake in a red-yellow latosol (Acrustox). Soil analysis showed that the most important changes were a marked increase in extractable iron and an inhibition of nitrification. The grass andropogon (Andropogon gayanus Kunth var.bisquamulatus (Hoechst) Hack) and the legume stylo (Stylosanthes capitata (Vog)) responded differently to reducing conditions.Andropogon showed low P, Ca, Mg, Fe and Mn content in the shoots but an intense coating of oxidized iron was observed on the surface of roots. Stylo plants, on the other hand, showed no iron deposition on the root surfaces but a high iron content in the shoots. No decreased P, Ca or Mg content was observed in this case. It was concluded that in water saturated soil, reduction took place and plant performance was affected not only by restricted root development but by preventing P, Ca and Mg uptake in andropogon and increasing Fe uptake in stylo plants. It is suggested that restricted P, Ca and Mg uptake by andropogen would be the result of iron deposition on root surfaces.     

Enhanced ototoxicity of gentamicin and salicylate caused by Mg deficiency and Zn deficiency

In rats, Mg deficiency caused a moderate hearing loss, measured by means of evoked potentials at 10 and 20 kHz, which was repaired after refeeding a normal diet. Application of 700 mg/kg salicylic acid or injection of 5×100 mg/kg gentamicin also caused a reversible hearing loss in normally fed rats. Treatment of Zn-deficient rats with salicylic acid produced a stronger although reversible hearing loss than in normally fed salicylate-treated rats. Treatment of Mg-deficient rats with gentamicin induced a strong hearing loss that was nearly complete and irreversible in 9 of 25 rats.     

Seasonal and species variation in the content of cadmium and associated metals in pasture plants at Shipham

Summary Very high Cd and Zn concentrations exist in soils reclaimed from old mine workings at Shipham but little of the metal is transferred into the pasture herbage. The amount of metal in the soil therefore only influences the amount in the aerial part of the plant to a small degree. It would appear to be the plant species which to a large extent governs its metal burden: grasses accumulating the least Cd and members of the Compositae the most.Within this species variation exists a change in metal content that corresponds to the time of year, setal levels in plants peaking in the winter between January and March. This increase in the metal content of the shoot reflects the redistribution of metal previously bound within the root. The movement of Pb may be associated with changes in the phosphate status of the plant. In grasses it would appear that the root possesses the highest metal burden, and forHolcus lanatus, tolerance to both Cd and Zn has been established. The ammonium-acetate and DTPA-extractable Zn/Cd ratio in soils corresponds closely to that found in the roots of both ryegrass and Yorkshire fog. A much higher ratio was observed in the shoots of these plants.     

Cultured human skin fibroblasts absorb65Zn

The radioactive isotope⁶⁵Zn was used to study the incorporation of zinc by cultured human skin fibroblasts. The development of the method for studying cell uptake of⁶⁵Zn in a minimal synthetic medium is presented. Kinetics carried out on control cultures up to 240 min indicated that zinc uptake occurred in three phases, the first being the most rapid. Temperature and pH affect zinc uptake, in favor of an active transport process. In addition, the rate of incorporation is considerably decreased during the first phases after adding potassium cyanide, during the last phases after adding sodium iodoacetate, and during all the phases if dithioerythritol is used. A hypothesis is therefore proposed according to which several types of mechanisms would be involved in zinc uptake by fibroblasts. At least a part of these mechanisms is energy-dependent.     

Spy1, a unique cell cycle regulator,alters viability in ALS motor neurons and cell lines in response to mutant SOD1-induced DNA damage

Increasing evidence indicates that DNA damage and p53 activation play major roles in the pathological process of motor neuron death in amyotrophic lateral sclerosis (ALS). Human SpeedyA1 (Spy1), a member of the Speedy/Ringo family, enhances cell proliferation and promotes tumorigenesis. Further studies have demonstrated that Spy1 promotes cell survival and inhibits DNA damage-induced apoptosis. We showed that the Spy1 expression levels were substantially decreased in ALS motor neurons compared with wild-type controls both in vivo and in vitro by qRT-PCR, western blotting, and Immunoassay tests. In addition, we established that over-expression of human SOD1 mutant G93A led to a decreased expression of Spy1. Furthermore, DNA damage response was activated in SOD1^G93A-transfected cells (mSOD1 cells). Moreover, decreased Spy1 expression reduced cell viability and further activated the DNA damage response in mSOD1 cells. In contrast, increased Spy1 expression improved cell viability and inhibited the DNA damage response in mSOD1 cells. These results suggest that Spy1 plays a protective role in ALS motor neurons. Importantly, these findings provide a novel direction for therapeutic options for patients with ALS as well as for trial designs, such as investigating the role of oncogenic proteins in ALS.     

Combined effect of temperature and zinc on Caenorhabditis elegans wild type and daf-21 mutant strains

Heavy metal pollution in aquatic ecosystems is a far reaching environmental problem. The possible influences of heavy metal exposure and the potential harm to organisms when combined with other environmental stressors such as temperature have been largely unexplored. An aquatic toxicity test of Caenorhabditis elegans was performed to estimate the 24 h median lethal concentration (LC₅₀) of different zinc concentrations at different temperatures (15 °C, 20 °C, 25 °C, and 30 °C). We also examined the time course thermotolerance on wild type (N2) and daf-21 null (JT6130) adults exposed to 6.1 mM zinc at 37 °C. Hsp90 protein expression level in response to the combined effect of temperature and zinc toxicity was also investigated by both Western blots and ELISA. Our results show that C. elegans wild type nematodes exhibit severe lethal toxicity after a 24 h exposure to zinc at higher temperatures. In addition, the expression level of Hsp90 was highly inhibited in adult worms subjected to zinc stress. This toxicity assay at different temperatures provides insight into organism response to combined effects of temperature and zinc toxicity.     

Targeting protein kinases benefits cancer immunotherapy

Small-molecule kinase inhibitors have been well established and successfully developed in the last decades for cancer target therapies. However, intrinsic or acquired drug resistance is becoming the major barrier for their clinical application. With the development of immunotherapies, in particular the discovery of immune checkpoint inhibitors (ICIs), the combination of ICIs with other therapies have recently been extensively explored, among which combination of ICIs with kinase inhibitors achieves promising clinical outcome in a plethora of cancer types. Here we comprehensively summarize the potent roles of protein kinases in modulating immune checkpoints both in tumor and immune cells, and reshaping tumor immune microenvironments by evoking innate immune response and neoantigen generation or presentation. Moreover, the clinical trial and approval of combined administration of kinase inhibitors with ICIs are collected, highlighting the precise strategies to benefit cancer immune therapies.