Synthesis and characterization of two novel isostructural polymeric 1D mono-halo-bridged octahedral copper (II) chains with a diaza-diamine ligand

Two novel isostructural (Π = 0.0045, I_v = 93.292) one-dimensional mono-halo-bridged octahedral copper (II) polymeric complexes [Cu(L)Cl]_n(ClO₄)_n (1) and [Cu(L)Br]_n(ClO₄)_n (2) (L = 1,9-diamino-5-methyl-5-nitro-3,7-diazanonane) were prepared and characterized by CHN, IR, EPR and magnetic moment studies under a tetra coordinating (diaza-diamine type) ligand environment. The X-ray structure analysis indicates that in both 1 and 2, independent consecutive [Cu(L)X]⁺ (X = Cl or Br) cations with crystallographic C_s symmetry propagate through the a glide plane of the orthorhombic space group Pnma to give the polymeric chain structure along the a axis. In 1, the Cu-Cl bond length is 2.740 which under bridging condition elongates to 3.024 and the bridging angle, Cu-Cl-Cu, is 164.9 while parameters for 2 are 2.961(2), 3.074(2) and 157.4(5), respectively. Each monomeric unit in both the complexes is under extensive intra and inter-molecular hydrogen bonding, leading to three dimensional structures.     

The specific binding of small molecule isoprenoids to rhoGDP dissociation inhibitor (rhoGDI)

The activities of small G-proteins are in part regulated by their interactions with GDI proteins. This binding is thought to be dependent on the C-terminal isoprenoid modification (geranylgeranyl or farnesyl) of these proteins. G-proteins are generally isoprenylated/methylated at their C-terminal cysteine residues. A quantitative fluorescence assay is reported here to evaluate the specificity of binding of rhoGDI. A rhodamine-labeled geranylgeranylated/methylated cysteine derivative is used to measure its binding to rhoGDI. Saturable binding in the low micromolar range is found with various geranylgeranylated/farnesylated analogues. Interestingly, the carboxymethylated derivatives bound significantly better than their free acid counterparts, suggesting that the state of methylation of the analogues is important for binding. The binding is also selective with respect to isoprenoid. Analogues containing hydrophobic modifications other than geranylgeranyl or farnesyl do not bind with significant affinities. These data demonstrate a substantial degree of specificity in the binding of isoprenoids to a protein important in signal transduction.     

Hybrid histidine kinases in pathogenic fungi

Histidine kinases (HK) sense and transduce via phosphorylation events many intra‐ and extracellular signals in bacteria, archaea, slime moulds and plants. HK are also widespread in the fungal kingdom, but their precise roles in the regulation of physiological processes remain largely obscure. Expanding genomic resources have recently given the opportunity to identify uncharacterised HK family members in yeasts and moulds and now allow proposing a complex classification of Basidiomycota, Ascomycota and lower fungi HK. A growing number of genetic approaches have progressively provided new insight into the role of several groups of HK in prominent fungal pathogens. In particular, a series of studies have revealed that members of group III HK, which occur in the highest number of fungal species and contain a unique N‐terminus region consisting of multiple HAMP domain repeats, regulate morphogenesis and virulence in various human, plant and insect pathogenic fungi. This research field is further supported by recent shape‐function studies providing clear correlation between structural properties and signalling states in group III HK. Since HK are absent in mammals, these represent interesting fungal target for the discovery of new antifungal drugs.     

Bacopaside-I Alleviates the Detrimental Effects of Acute Paraquat Intoxication in the Adult Zebrafish Brain

Neurochemical Research - Paraquat (PQ), an environmental neurotoxicant, causes acute fatal poisoning upon accidental or intentional ingestion (suicidal cases) worldwide. To date, an effective...     

Unfolded protein response during cardiovascular disorders: a tilt towards pro-survival and cellular homeostasis

Molecular and Cellular Biochemistry - The endoplasmic reticulum (ER) is an organelle that orchestrates the production and proper assembly of an extensive types of secretory and membrane proteins....     

Sphingolipidomics of drug resistant Candida auris clinical isolates reveal distinct sphingolipid species signatures

Independent studies from our group and others have provided evidence that sphingolipids (SLs) influence the antimycotic susceptibility of Candida species. We analyzed the molecular SL signatures of drug-resistant clinical isolates of Candida auris, which have emerged as a global threat over the last decade. This included Indian hospital isolates of C. auris, which were either resistant to fluconazole (FLC^R) or amphotericin B (AmB^R) or both drugs. Relative to Candida glabrata and Candida albicans strains, these C. auris isolates were susceptible to SL pathway inhibitors such as myriocin and aureobasidin A, suggesting that SL content may influence azole and AmB susceptibilities. Our analysis of SLs confirmed the presence of 140 SL species within nine major SL classes, namely the sphingoid bases, Cer, αOH-Cer, dhCer, PCer, αOH-PCer, αOH-GlcCer, GlcCer, and IPC. Other than for αOH-GlcCer, most of the SLs were found at higher concentrations in FLC^R isolates as compared to the AmB^R isolates. SLs were at intermediate levels in FLC^R + AmB^R isolates. The observed diversity of molecular species of SL classes based on fatty acyl composition was further reflected in their distinct specific imprint, suggesting their influence in drug resistance. Together, the presented data improves our understanding of the dynamics of SL structures, their synthesis, and link to the drug resistance in C. auris.     

Palmitate exacerbates bisphenol A toxicity via induction of ER stress and mitochondrial dysfunction

Combined exposure to dietary nutrients and environmental chemicals may elicit significantly different physiological effects than single exposures. Exposure to dietary saturated fats and environmental toxins is a physiologically-significant dual exposure that is particularly associated with lower socioeconomic status, potentially placing these individuals at heightened risk of xenobiotic toxicities. However, no prior studies have examined interactions between specific lipids and environmental xenobiotics in modulating cellular health. Using primary mouse embryonic fibroblasts, we have discovered that prior exposure to the saturated fatty acid, palmitate, exacerbates cellular toxicity associated with the industrial plasticizer, bisphenol A (BPA). Cell death upon BPA exposure following palmitate pre-treatment was greater than that occurring with either exposure alone. Mechanistically, cell death was preceded by increased endoplasmic reticulum stress and loss of mitochondrial membrane potential in palmitate plus BPA exposed cells, leading to increased caspase-3 cleavage and subsequent apoptosis. Interestingly, inclusion of the unsaturated fatty acid, oleate, along with palmitate during the pre-treatment period completely abrogated the ER stress, mitochondrial toxicity, and cell death induced by subsequent exposure to BPA. Thus, our data identify for the first time an important interaction between a fatty acid and an environmental toxin and have implications for developing nutritional interventions to mitigate the deleterious effects of such xenobiotic exposures.     

Inheritance and molecular mapping of a gibberellin-insensitive dwarf mutant in groundnut (<Emphasis Type="Italic">Arachis hypogaea</Emphasis> L.)

A dark green dwarf mutant, TGM 167, was isolated from a gamma ray + sodium azide mutagenised population of cultivated groundnut breeding line, TFDRG 5. The mutant had a 45.8% reduction in height due to its shorter internodal length. Further, it was found to be insensitive towards exogenous GA₃ application, although it had nearly the same level of endogenous GA₃ as the parent. Genetic analysis revealed that the dwarfism is under the control of a single dominant gene. This dominant dwarfing gene was mapped with an SSR marker TC3H02 at a distance of 9.7 cM.