Hydrocoryne iemanja (Cnidaria), a new species of Hydrozoa with unusual mode of asexual reproduction

Hydrocoryne iemanja sp. nov. was found in an aquarium, growing on rhodoliths of coralline algae collected on the southeastern coast of Brazil (20 degrees 40`S 40 degrees 2`W). The colonies were reared through maturity in the laboratory. Each colony had up to 7 sessile, long and thin monomorphic zooids, very extensible and flexible, arising from a chitinous, hard dark-brown plate with minute spines. Medusae budded from near the basal part of hydrocaulus, and were released in immature condition, acquiring fully developed interradial gonads 5-7 days after release. Asexual reproduction by longitudinal fission was observed on the hydrocaulus of the polyps, both for those in normal condition and those with injuries. Fission started at the oral region, extending aborally, with a new hard plate formed in the basal part of hydrocaulus. When fission reached the new hard plate, the new polyp detached, becoming free and sinking to the bottom, starting a new colony. Detached polyps were morphologically indistinguishable from other polyps, being able to produce medusae. Mother and daughter polyps undertook subsequent fissions. This mode of longitudinal fission is distinct from other modes of longitudinal fission, a process known for a few species Of cnidarians. Further studies of this process may shed light on the understanding of the evolutionary pathways in Cnidaria and animals. Hydrocoryne iemanja sp. nov. is distinguishable from its two congeners by the distinct marginal tentacles of the medusae-short and with a median nematocyst knob-an unambiguous character useful even for the identification Of newly liberated medusae.

QUALITY OF LIFE IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS IN NORTHEASTERN BRAZIL: IS HEALTH-RELATED QUALITY OF LIFE A PREDICTOR OF SURVIVAL FOR THESE PATIENTS?

Objective: To identify social, demographic and clinical characteristics that influence survival of patients with systemic lupus erythematosus (SLE). Methods: Sixty-three patients with a diagnosis of SLE were studied at our medical services in 1999 and then reviewed in 2005. We utilized a protocol to obtain demographic and clinical traits, activity and damage indices, and health-related quality of life via the SF-36. All statistical tests were performed using a significance level of 5%. Results: Out of the 63 patients examined in 1999, six died, four were lost for the follow-up and the previous protocol was applied to the remaining 53 patients. The six patients who died presented the worst recorded health-related quality of fife, in all aspects. The most important observed predictor of death was a mean lower score in the Role-Emotional Domain of the mental health component of the SF-36 (p<0.01). Conclusion: Health-related quality of life may be used as possible predictive factor of mortality among patients with SLE.

Methods and strategies to identify the mode of action of phytoactive compounds

Small molecules affecting biological processes in plants are widely used in agricultural practice as herbicides or plant growth regulators and in basic plant sciences as probes to study the physiology of plants. Most of the compounds were identified in large screens by the agrochemical industry, as phytoactive natural products and more recently, novel phytoactive compounds originated from academic research by chemical screens performed to induce specific phenotypes of interest. The aim of the present PhD thesis is to evaluate different approaches used for the identification of the primary mode of action (MoA) of a phytoactive compound. Based on the methodologies used for MoA identification, three approaches are discerned: a phenotyping approach, an approach based on a genetic screen and a biochemical screening approach.rnFour scientific publications resulting from my work are presented as examples of how a phenotyping approach can successfully be applied to describe the plant MoA of different compounds in detail.rnI. A subgroup of cyanoacrylates has been discovered as plant growth inhibitors. A set of bioassays indicated a specific effect on cell division. Cytological investigations of the cell division process in plant cell cultures, studies of microtubule assembly with green fluorescent protein marker lines in vivo and cross resistant studies with Eleusine indica plants harbouring a mutation in alpha-tubulin, led to the description of alpha-tubulin as a target site of cyanoacrylates (Tresch et al., 2005).rnII. The MoA of the herbicide flamprop-m-methyl was not known so far. The studies described in Tresch et al. (2008) indicate a primary effect on cell division. Detailed studies unravelled a specific effect on mitotic microtubule figures, causing a block in cell division. In contrast to other inhibitors of microtubule rearrangement such as dinitroanilines, flamprop-m-methyl did not influence microtubule assembly in vitro. An influence of flamprop-m-methyl on a target within the cytoskeleton signalling network could be proposed (Tresch et al., 2008).rnIII. The herbicide endothall is a protein phosphatase inhibitor structurally related to the natural product cantharidin. Bioassay studies indicated a dominant effect on dark-growing cells that was unrelated to effects observed in the light. Cytological characterisation of the microtubule cytoskeleton in corn tissue and heterotrophic tobacco cells showed a specific effect of endothall on mitotic spindle formation and ultrastructure of the nucleus in combination with a decrease of the proliferation index. The observed effects are similar to those of other protein phosphatase inhibitors such as cantharidin and the structurally different okadaic acid. Additionally, the observed effects show similarities to knock-out lines of the TON1 pathway, a protein phosphatase-regulated signalling pathway. The data presented in Tresch et al. (2011) associate endothall’s known in vitro inhibition of protein phosphatases with in vivo-effects and suggest an interaction between endothall and the TON1 pathway.rnIV. Mefluidide as a plant growth regulator induces growth retardation and a specific phenotype indicating an inhibition of fatty acid biosynthesis. A test of the cuticle functionality suggested a defect in the biosynthesis of very-long-chain fatty acids (VLCFA) or waxes. Metabolic profiling studies showed similarities with different groups of VLCFA synthesis inhibitors. Detailed analyses of VLCFA composition in tissues of duckweed (Lemna paucicostata) indicated a specific inhibition of the known herbicide target 3 ketoacyl-CoA synthase (KCS). Inhibitor studies using a yeast expression system established for plant KCS proteins verified the potency of mefluidide as an inhibitor of plant KCS enzymes. It could be shown that the strength of inhibition varied for different KCS homologues. The Arabidopsis Cer6 protein, which induces a plant growth phenotype similar to mefluidide when knocked out, was one of the most sensitive KCS enzymes (Tresch et al., 2012).rnThe findings of my own work were combined with other publications reporting a successful identification of the MoA and primary target proteins of different compounds or compound classes.rnA revised three-tier approach for the MoA identification of phytoactive compounds is proposed. The approach consists of a 1st level aiming to address compound stability, uniformity of effects in different species, general cytotoxicity and the effect on common processes like transcription and translation. Based on these findings advanced studies can be defined to start the 2nd level of MoA characterisation, either with further phenotypic characterisation, starting a genetic screen or establishing a biochemical screen. At the 3rd level, enzyme assays or protein affinity studies should show the activity of the compound on the hypothesized target and should associate the in vitro effects with the in vivo profile of the compound.

The binding mode of side chain- and C3-modified epothilones to tubulin

The tubulin-binding mode of C3- and C15-modified analogues of epothilone A (Epo A) was determined by NMR spectroscopy and computational methods and compared with the existing structural models of tubulin-bound natural Epo A. Only minor differences were observed in the conformation of the macrocycle between Epo A and the C3-modified analogues investigated. In particular, 3-deoxy- (compound 2) and 3-deoxy-2,3-didehydro-Epo A (3) were found to adopt similar conformations in the tubulin-binding cleft as Epo A, thus indicating that the 3-OH group is not essential for epothilones to assume their bioactive conformation. None of the available models of the tubulin-epothilone complex is able to fully recapitulate the differences in tubulin-polymerizing activity and microtubule-binding affinity between C20-modified epothilones 6 (C20-propyl), 7 (C20-butyl), and 8 (C20-hydroxypropyl). Based on the results of transferred NOE experiments in the presence of tubulin, the isomeric C15 quinoline-based Epo B analogues 4 and 5 show very similar orientations of the side chain, irrespective of the position of the nitrogen atom in the quinoline ring. The quinoline side chain stacks on the imidazole moiety of beta-His227 with equal efficiency in both cases, thus suggesting that the aromatic side chain moiety in epothilones contributes to tubulin binding through strong van der Waals interactions with the protein rather than hydrogen bonding involving the heteroaromatic nitrogen atom. These conclusions are in line with existing tubulin polymerization and microtubule-binding data for 4, 5, and Epo B.

Do N-arachidonyl-glycine (NA-glycine) and 2-arachidonoyl glycerol (2-AG) share mode of action and the binding site on the β 2 subunit of GABA A receptors?

NA-glycine is an endogenous lipid molecule with analgesic properties, which is structurally similar to the endocannabinoids 2-AG and anandamide but does not interact with cannabinoid receptors. NA-glycine has been suggested to act at the G-protein coupled receptors GPR18 and GPR92. Recently, we have described that NA-glycine can also modulate recombinant α1β2γ2 GABAA receptors. Here we characterize in more detail this modulation and investigate the relationship of its binding site with that of the endocannabinoid 2-AG.

The Cytotoxic Mode of Action of the Venom of Cupiennius salei (Ctenidae)

The venom of the ctenid spider Cupiennius salei (Fig.16.1) is rich in components which belong to different functional groups. Besides low molecular mass compounds, the venom contains several disulphide-rich peptides, also called mini-proteins, which act as neurotoxins on ion channels or as enhancers of neurotoxins. Likewise, a variety of small cytolytic peptides, which destroy membranes very efficiently, and enzymes are present in the venom. Neurotoxins with cytolytic activity, cytolytic a-helical small cationic peptides and enzymes most probably attacking connective tissue and phospholipid membranes cause the overall cytotoxic effect of this venom. Synergistic and enhancing interactions between components enable the spider to achieve a maximum of toxicity with a minimum of venom quantity.

Subjective well-being and exercise in the second halt of life: a critical review of theoretical approaches

Research has shown repeatedly that the “feeling better” effect of exercise is far more moderate than generally claimed. Examinations of subgroups in secondary analyses also indicate that numerous further variables influence this relationship. One reason for inconsistencies in this research field is the lack of adequate theoretical analyses. Well-being output variables frequently possess no construct definition, and little attention is paid to moderating and mediating variables. This article integrates the main models in an overview and analyzes how secondary analyses define well-being and which areas of the construct they focus on. It then applies a moderator and/or mediator framework to examine which person and environmental variables can be found in the existing explanatory approaches in sport science and how they specify the influence of these moderating and mediating variables. Results show that the broad understanding of well-being in many secondary analyses makes findings difficult to interpret. Moreover, physiological explanatory approaches focus more on affective changes in well-being, whereas psychological approaches also include cognitive changes. The approaches focus mostly on either physical or psychological person variables and rarely combine the two, as in, for example, the dual-mode model. Whereas environmental variables specifying the treatment more closely (e.g., its intensity) are comparatively frequent, only the social support model formulates variables such as the framework in which exercise is presented. The majority of explanatory approaches use simple moderator and/or mediator models such as the basic mediated (e.g., distraction hypothesis) or multiple mediated (e.g., monoamine hypotheses) model. The discussion draws conclusions for future research.

Functionally Optimized Neuritogenic Farinosone C Analogs: SAR-Study and Investigations on Their Mode of Action

Several natural products derived from entomopathogenic fungi have been shown to initiate neuronal differentiation in the rat pheochromocytoma PC12 cell line. After the successful completion of the total synthesis program, the reduction of structural complexity while retaining biological activity was targeted. In this study, farinosone C served as a lead structure and inspired the preparation of small molecules with reduced complexity, of which several were able to induce neurite outgrowth. This allowed for the elaboration of a detailed structure-activity relationship. Investigations on the mode of action utilizing a computational similarity ensemble approach suggested the involvement of the endocannabinoid system as potential target for our analogs and also led to the discovery of four potent new endocannabinoid transport inhibitors.

Memorandum on the law and the facts in the matter of the claim of China against Mexico for losses of life and property suffered by Chinese subjects at Torreón on May 13, 14, and 15, 1911.

"English & Spanish."

Essays on important subjects : intended to establish the doctrine of salvation by grace and to point out its influence on holiness of life /

v. 1. Essay on the connexion between the doctrine of justification by the imputed righteousness of Christ, and holiness of life. The absolute necessity of salvation through Christ. The trial of religious truth by its moral influence. The charge of sedition and faction against good men, especially faithful ministers, considered and accounted for. Prayer for national prosperity and for the revival of religion inseparably connected -- v. 2. A serious enquiry into the nature and effects of the stage. Ecclesiastical characteristics -- v. 3. A practical treatise on regeneration.

""Star of Life" - emergency medical care symbol: background, specifications, and criteria.

Mode of access: Internet.

Length of life; a study of the life table,

"List of sources": p. 359-363. Bibliographical footnotes.

Ascaris : the biologist's story of life /

Mode of access: Internet.

A formula for a better way of life; an informal chat with you ... A business man tells how he does it.

Mode of access: Internet.