Bioactive compounds sourced from Terminalia spp. in bacterial malodour prevention: an effective alternative to chemical additives.

OBJECTIVE: Recently, our group reported that extracts prepared from the Australian native plant Terminalia ferdinandiana Exell. are potent inhibitors of the growth malodorous bacteria with similar efficacy to triclosan and through these results, we highlighted a potential biological alternative to the current chemical additives. Other members of the genus Terminalia are also well documented for their antibacterial potential and tannin contents and thus were investigated as potential deodorant additives. METHODS: Solvent extractions prepared from of selected Indian, Australian and South African Terminalia spp. were screened by disc diffusion and liquid dilution assays against C. jeikeium, S. epidermidis, P. acnes and B. linens. The antibacterial activity was quantified by liquid dilution MIC assays. The extracts were screened for toxicity using Atremia franciscana nauplii and HDF cell viability bioassays. High-resolution time-of-flight (TOF) LC-MS and GC-MS headspace fingerprint analysis was used to detect tannin, flavonoid and terpenoid components in the extracts. RESULTS: Bacterial growth inhibition was observed in all Terminalia extracts with the methanolic T. chebula, T. carpenteriae and T. sericea extracts the most promising bacterial growth inhibitors, yielding MIC values as low as 200 µg mL-1 . Toxicity analyses of the extracts were favourable, and we determined that the methanolic T. chebula, T. carpenteriae and T. sericea extracts were all non-toxic. Using previously detected T. ferdinandiana antimicrobials as benchmarks, LC-MS and GC-MS fingerprint analyses revealed similar compounds in the methanolic T. chebula, T. carpenteriae and T. sericea extracts. CONCLUSION: Through these results, we propose that Terminalia spp. extracts may be useful deodorant additives to inhibit the growth of axillary and plantar malodorous bacteria, offering a biological alternative to their chemically synthesized counterparts.

OBJECTIF: notre groupe a récemment signalé que les extraits de la plante native d'Australie Terminalia ferdinandiana Exell sont de puissants inhibiteurs de croissance pour les bactéries responsables de mauvaises odeurs. Leur efficacité est comparable à celle du triclosan. Ces résultats nous ont permis de mettre en avant la possibilité d'une alternative biologique aux additifs chimiques utilisés aujourd'hui. D'autres membres du genre Terminalia, également bien connus pour leur potentiel antibactérien et leur taux de tanin, ont eux aussi été examinés comme additifs potentiels pour les déodorants. MÉTHODES: extractions par solvant préparées à partir de spécimens de Terminalia spp. d'Inde, d'Australie et d'Afrique du Sud, sélectionnés par diffusion (méthode des disques) et par des dosages de dilution liquide, contre C. Jeikeium, S. Epidermidis, P. Acnes et B. Linens. L'activité antibactérienne a été quantifiée à l'aide d'analyses de la CMI en dilution liquide. La toxicité des extraits a été recherchée à l'aide d'Atremia franciscana nauplii et de dosages biologiques de la viabilité cellulaire de fibroblastes dermiques humains (FDH). Pour détecter les composants tanniques, flavonoïdes et terpénoïdes dans les extraits, on a procédé à une analyse d'identification de l'espace de tête par LC-MS et GC-MS à temps de vol (TOF) à haute résolution. RÉSULTATS: On a observé une inhibition de la croissance bactérienne dans tous les extraits de Terminalia avec les extraits méthanoliques de T. Chebula, T. Carpenteriae et T. Sericea, les inhibiteurs de croissance bactérienne les plus prometteurs, ayant des valeurs de CMI pouvant être aussi faibles que 200 µg/ml_ 1. Les analyses de toxicité des extraits ont donné des résultats favorables et nous avons pu établir que les extraits méthanoliques de T. Chebula, T. Carpenteriae et T. Sericea étaient tous non toxiques. En utilisant les antimicrobiens déjà repérés T. Ferdinandiana comme des points de repère, les analyses d'identification par LC-MS et GC-MS ont révélé la présence de composés similaires dans les extraits méthanoliques de T. Chebula, T. Carpenteriae et T. Sericea. CONCLUSION: D'après ces résultats, nous pensons que les extraits de Terminalia spp. peuvent constituer des additifs utiles pour les déodorants grâce à leur pouvoir d'inhibition de la croissance des bactéries responsables des mauvaises odeurs de pieds et d'aisselles, offrant ainsi une alternative biologique à leurs équivalents d'origine chimiosynthétique.

Quantitative chemoproteomic profiling reveals multiple target interactions of spongiolactone derivatives in leukemia cells.

The spongiolactones are marine natural products with an unusual rearranged spongiane skeleton and a fused ß-lactone ring. These compounds have potential anticancer properties but their mode of action has yet to be explored. Here we employ activity-based protein profiling to identify the targets of a more potent spongiolactone derivative in live cancer cells, and compare these to the targets of a simpler ß-lactone. These hits provide the first insights into the covalent mechanism of action of this natural product class.

Terminalia ferdinandiana Exell. Extracts inhibit the growth of body odour-forming bacteria.

OBJECTIVE: Terminalia ferdinandiana extracts are potent growth inhibitors of many bacterial pathogens. They may also inhibit the growth of malodour-producing bacteria and thus be useful deodorant components, although this is yet to be tested. METHODS: Terminalia ferdinandiana fruit and leaf solvent extracts were investigated by disc diffusion and liquid dilution MIC assays against the most significant bacterial contributors to axillary and plantar malodour formation. Toxicity was determined using the Artemia franciscana nauplii bioassay. Non-targeted HPLC separation of the methanolic leaf extract coupled to high-resolution time-of-flight (TOF) mass spectroscopy was used for the identification and characterization of individual components in the extract. RESULTS: The T. ferdinandiana leaf extracts were the most potent bacterial growth inhibitors. The leaf methanolic extract was particularly potent, with low MIC values against C. jeikeium (233 µg mL-1 ), S. epidermidis (220 µg mL-1 ), P. acnes (625 µg mL-1 ) and B. linens (523 µg mL-1 ). The aqueous and ethyl acetate leaf extracts were also potent growth inhibitors of C. jeikeium and S. epidermidis (MICs < 1000 µg mL-1 ). In comparison, the fruit extracts were substantially less potent antibacterial agents, although still with MIC values indicative of moderate growth inhibitory activity. All T. ferdinandiana leaf extracts were non-toxic in the Artemia franciscana bioassay. Non-biased phytochemical analysis of the methanolic leaf extract revealed the presence of high levels of and high diversity of tannins and high levels of the flavone luteolin. CONCLUSION: The low toxicity of the T. ferdinandiana leaf extracts and their potent growth inhibition of axillary and plantar malodour-producing bacteria indicate their potential as deodorant components.

Correction: Chemical proteomics approaches for identifying the cellular targets of natural products.

Correction for 'Chemical proteomics approaches for identifying the cellular targets of natural products' by M. H. Wright et al., Nat. Prod. Rep., 2016, DOI: 10.1039/c6np00001k.

Chemical proteomics approaches for identifying the cellular targets of natural products.

Covering: 2010 up to 2016Deconvoluting the mode of action of natural products and drugs remains one of the biggest challenges in chemistry and biology today. Chemical proteomics is a growing area of chemical biology that seeks to design small molecule probes to understand protein function. In the context of natural products, chemical proteomics can be used to identify the protein binding partners or targets of small molecules in live cells. Here, we highlight recent examples of chemical probes based on natural products and their application for target identification. The review focuses on probes that can be covalently linked to their target proteins (either via intrinsic chemical reactivity or via the introduction of photocrosslinkers), and can be applied "in situ" - in living systems rather than cell lysates. We also focus here on strategies that employ a click reaction, the copper-catalysed azide-alkyne cycloaddition reaction (CuAAC), to allow minimal functionalisation of natural product scaffolds with an alkyne or azide tag. We also discuss 'competitive mode' approaches that screen for natural products that compete with a well-characterised chemical probe for binding to a particular set of protein targets. Fuelled by advances in mass spectrometry instrumentation and bioinformatics, many modern strategies are now embracing quantitative proteomics to help define the true interacting partners of probes, and we highlight the opportunities this rapidly evolving technology provides in chemical proteomics. Finally, some of the limitations and challenges of chemical proteomics approaches are discussed.

Interaction of PLD1b with actin in antigen-stimulated mast cells.

Phosphatidic acid, the product of phospholipase D catalysed phosphatidylcholine hydrolysis is an important signalling molecule that has been implicated in regulation of actin cytoskeleton remodelling and secretion from mast cells. We show that human PLD1b (hPLD1b) is an actin-binding protein and the N-terminus is predominantly involved in this interaction. Protein kinase C (PKC) is a major upstream regulator of PLD activity and PKC phosphorylation sites have been identified within the N-terminus of PLD1b at serine 2 and threonine 147. Over-expression of wild type hPLD1b in mast cells showed that antigen stimulation significantly enhanced co-localisation of PLD1b with actin structures. Mutation of serine 2 to alanine abolished antigen-induced co-localisation whereas mutation of threonine 147 had less dramatic effects on co-localisation. The absence of co-localisation of PLD1b (S2A) with actin coincides with a significant decrease in PLD activity in cells expressing the PLD1b (S2A) mutant. In resting RBL-2H3 cells, mutation of serine 2 to aspartate resulted in constitutive co-localisation of PLD with the actin cytoskeleton, coincident with restored PLD activity. These results reveal that serine 2 is an important regulatory site involved in controlling PLD enzyme activity and the interaction between PLD and actin.

Zero-bias anomaly and kondo-assisted quasiballistic 2D transport.

Nonequilibrium transport measurements in mesoscopic quasiballistic 2D electron systems show an enhancement in the differential conductance around the Fermi energy. At very low temperatures, such a zero-bias anomaly splits, leading to a suppression of linear transport at low energies. We also observed a scaling of the nonequilibrium characteristics at low energies which resembles electron scattering by two-state systems, addressed in the framework of two-channel Kondo model. Detailed sample-to-sample reproducibility indicates an intrinsic phenomenon in unconfined 2D systems in the low electron-density regime.

Neuroanatomy in elbow arthroscopy.

An injury to the median nerve from within the joint during an arthroscopic synovectomy prompted a study of the relationship of the nerves to the capsule and bones of the elbow. Six pairs of cadaveric elbows frozen in 90 degrees of flexion and one pair frozen in extension were sectioned at 5-mm intervals, and the distances from the major nerves to the bones and capsule were recorded. One elbow joint in each pair was filled with saline solution. Saline solution insufflation increased the nerve-to-bone distance with the elbow in flexion. The results were 12 mm for the median nerve and 6 mm for the radial nerve. The capsule-to-nerve distance was affected little by insufflation and was as narrow as 6 mm in three specimens. Extension eliminated the protective effects of insufflation and brought the nerves closer to the bone. These findings confirm (1) the importance of flexion and insufflation in portal placement, (2) that insufflation does not improve the capsule-to-nerve distance, and (3) the potential for "from within-out" injury in synovial procedures.

Poly(L-alanine) as a universal reference material for understanding protein energies and structures.

We present a proposition, the "poly(L-alanine) hypothesis," which asserts that the native backbone geometry for any polypeptide or protein of M residues has a closely mimicking, mechanically stable, image in poly(L-alanine) of the same number of residues. Using a molecular mechanics force field to represent the relevant potential energy hypersurfaces, we have carried out calculations over a wide range of M values to show that poly(L-alanine) possesses the structural versatility necessary to satisfy the proposition. These include poly(L-alanine) representatives of minima corresponding to secondary and supersecondary structures, as well as poly(L-alanine) images for tertiary structures of the naturally occurring proteins bovine pancreatic trypsin inhibitor, crambin, ribonuclease A, and superoxide dismutase. The successful validation of the hypothesis presented in this paper indicates that poly(L-alanine) will serve as a good reference material in thermodynamic perturbation theory and calculations aimed at evaluating relative free energies for competing candidate tertiary structures in real polypeptides and proteins.

Alcoholics' and nonalcoholics' attributions of control of future life events.

Alcoholic and nonalcoholic subjects rated the degree of control that they and others possess over future life events. Alcoholics attributed less personal control over events to themselves than nonalcoholics did. Alcoholics also attributed less control to themselves than to others, whereas nonalcoholics attributed more control to themselves than to others. These differences prevailed despite the similar socioeconomic and demographic characteristics, recent life experiences and beliefs concerning the general controllability of events of both alcoholics and nonalcoholics. The attributions of alcoholics were consistent with others' notions of self-handicapping. The attributions of nonalcoholics were consistent with control motivation. Alcoholics who attributed less control to themselves than to others more frequently failed to complete treatment than did alcoholics who attributed more control to themselves.

Functional use of secondary cancer symptomatology.

This article presents several case studies which illustrate the way in which a terminal patient's attention may be diverted from the primary disease process, cancer, to secondary somatic symptomatology such as pain and nausea. This phenomenon has important consequences for the patient, family, physician, and the patient's medical treatment. These consequences are discussed in terms of primary gain, tertiary gain, and the "medicalization of existential problems."

Learned helplessness and learned effectiveness: effects of explicit response cues on individuals differing in personal control expectancies.

Female undergraduates (n = 62) who scored as extreme internals or externals on the Mirels Personal Fate Control Scale participated in a partial replication of Hiroto's learned helplessness experiment. Lights were added to the treatment apparatus, which made explicit to subjects the contingency or noncontingency between their responses and the termination of an aversive tone. As predicted, the performance of internals was significantly impaired by uncontrollability (learned helplessness), while that of externals was facilitated by controllability (learned effectiveness). Externals performed as well as internals in the "escapable" condition, but their performance was inferior to that of internals in the control condition. Following "inescapable" treatment, internals performed worse than externals. These results are supportive of Lefcourt's theory of cue explication. Implications for locus of control and learned helplessness research are discussed.