Antimicrobial compounds of fungi vectored by Clusia spp. (Clusiaceae) pollinating bees

The production of antimicrobial compounds by fungi associated with Clusia spp. pollinating bees (Trigona sp., Trigonini) was investigated in order to approach natural mechanisms of microbial density control within nest environment. By using a bioassay-guided approach based on bioautography and minimal inhibitory concentration (MIC), known alpha,beta-dehydrocurvularin and curvularin were isolated from Curvularia eragrostidis (CCT 5634) and Curvularia pallescens (CCT 5654), and known cochlioquinone A and isocochlioquinone A were isolated from Drechslera dematioidea (CCT 5631).     

The N-terminal domains of TRF1 and TRF2 regulate their ability to condense telomeric DNA

TRF1 and TRF2 are key proteins in human telomeres, which, despite their similarities, have different behaviors upon DNA binding. Previous work has shown that unlike TRF1, TRF2 condenses telomeric, thus creating consequential negative torsion on the adjacent DNA, a property that is thought to lead to the stimulation of single-strand invasion and was proposed to favor telomeric DNA looping. In this report, we show that these activities, originating from the central TRFH domain of TRF2, are also displayed by the TRFH domain of TRF1 but are repressed in the full-length protein by the presence of an acidic domain at the N-terminus. Strikingly, a similar repression is observed on TRF2 through the binding of a TERRA-like RNA molecule to the N-terminus of TRF2. Phylogenetic and biochemical studies suggest that the N-terminal domains of TRF proteins originate from a gradual extension of the coding sequences of a duplicated ancestral gene with a consequential progressive alteration of the biochemical properties of these proteins. Overall, these data suggest that the N-termini of TRF1 and TRF2 have evolved to finely regulate their ability to condense DNA.     

TRF2/RAP1 and DNA–PK mediate a double protection against joining at telomeric ends

DNA-dependent protein kinase (DNA-PK) is a double-strand breaks repair complex, the subunits of which (KU and DNA-PKcs) are paradoxically present at mammalian telomeres. Telomere fusion has been reported in cells lacking these proteins, raising two questions: how is DNA–PK prevented from initiating classical ligase IV (LIG4)-dependent non-homologous end-joining (C-NHEJ) at telomeres and how is the backup end-joining (EJ) activity (B-NHEJ) that operates at telomeres under conditions of C-NHEJ deficiency controlled? To address these questions, we have investigated EJ using plasmid substrates bearing double-stranded telomeric tracks and human cell extracts with variable C-NHEJ or B-NHEJ activity. We found that (1) TRF2/RAP1 prevents C-NHEJ-mediated end fusion at the initial DNA–PK end binding and activation step and (2) DNA–PK counteracts a potent LIG4-independent EJ mechanism. Thus, telomeres are protected against EJ by a lock with two bolts. These results account for observations with mammalian models and underline the importance of alternative non-classical EJ pathways for telomere fusions in cells.     

Discovery and SAR of new benzazepines as potent and selective 5-HT(2C) receptor agonists for the treatment of obesity

We report on the synthesis, biological evaluation and structure-activity relationships for a series of 3-benzazepine derivatives as 5-HT(2C) receptor agonists. The compounds were evaluated in functional assays measuring [3H] phosphoinositol turnover in HEK-293 cells transiently transfected with h5-HT(2C), h5-HT(2A) or h5-HT(2B) receptors. Several compounds are shown to be potent and selective 5-HT(2C) receptor agonists, which decrease food intake in a rat feeding model.     

Effect of nitrogen on Passiflora suberosa L. (Passifloraceae) and consequences for larval performance and oviposition in Heliconius erato phyllis (Fabricius) (Lepidoptera: Nymphalidae)

The present study examines the influence of nitrogen on growth rates, morphological and nutritional characteristics of Passiflora suberosa L., and the corresponding consequences for Heliconius erato phyllis (Fabricius) growth and oviposition. The treatments consisted of different nitrogen doses (0, 150 and 300 mg L(-1)) applied to the soil. Newly emerged larvae were individually reared in the laboratory (25+/-1 degree C) on branches of P. suberosa obtained from plants grown under the three nitrogen levels, and field collected females were submitted to oviposition choice tests. P. suberosa growth rates, leaf area and internode length increased significantly when grown with nitrogen enriched soil. P. suberosa presented significantly greater leaf toughness when grown without nitrogen addition. Leaves of this species also presented lower water content and toughness. Nitrogen addition increased the concentration of nitrogen and potassium on plant leaf tissues. The greater nitrogen concentration on plants did not affect H. erato phyllis larval survival, but led to a reduction in larval development time and increased adult size. Females significantly preferred to lay eggs in plants cultivated in nitrogen enriched soil. This choice was positively correlated with larval performance, which could be a possible explanation for the maintenance of that behaviour, as well as the choice of larger branches as reported in previous studies.     

Effect of high external pressures on the vibrational spectra of crystalline dichloro(1,5-cycloctadiene)platinum(II), Pt(η-C8H12)Cl2

The effects of high external pressures on the principal IR and Raman bands of crystalline dichloro(1,5-cycloctadiene)platinum(II), Pt(COD)Cl₂ (COD = η⁴-C₈H₁₂), have been investigated for pressures up to ∼30 kbar by diamond-anvil cell microspectroscopy. This square-planar Pt(II) complex does not undergo any pressure-induced structural change throughout the pressure range investigated and the pressure dependences (dν/dP) for the vibrational modes range from −0.18 to 0.79 cm⁻¹ kbar⁻¹. The negative dν/dP value observed for the IR band at 1426 cm⁻¹ (−0.18 cm⁻¹ kbar⁻¹) suggests that this band is chiefly associated with a CC stretching mode of the Pt-COD group. This observation provides yet another indication that high-pressure vibrational spectroscopy may indeed be a general method for establishing the presence of π-backbonding in organometallic complexes, such as metal carbonyls and alkenes.     

Pyrazolone methylamino piperidine derivatives as novel CCR3 antagonists

The discovery and optimization of a novel class of potent CCR3 antagonists is described. Details of synthesis and SAR are given together with some ADME properties of selected compounds. An optimal balance between activities, physicochemical properties, and in vitro metabolic stability was reached by the proper choice of substituents.     

Microbial reduction of cyclohexanones

A Brazilian strain of the bacteria Serratia rubidaea CCT 5742 quantitatively reduced 4-tert-butylcyclohexanone and 4-methylcyclohexanone to the less thermodynamically stable diastereoisomeric alcohols cis-4-tert-butylcyclohexanol and cis-4-methylcyclohexanol with a diastereoisomeric excesses (de) of 96% and 44%, respectively. 2-Methylcyclohexanone was also totally reduced to the corresponding alcohols affording the trans-(+)-(1S, 2S)-2-methylcyclohexanol with 78% of de and an enantiomeric excess (ee) of 80%. The cis-(+)-(1S, 2R)-2-methylcyclohexanol was obtained in 98% ee.     

A new Brazilian Passiflora leafminer: Spinivalva gaucha,gen. n., sp. n. (Lepidoptera,Gracillariidae, Gracillariinae), the first gracillariid without a sap-feeding instar

Male, female, pupa, larva and egg of a new genus and species of Gracillariidae (Gracillariinae), Spinivalva gaucha Moreira and Vargas from southern Brazil are described and illustrated with the aid of optical and scanning electron microscopy. A preliminary analysis of mitochondrial DNA sequences including members of related lineages is also provided. The immature stages are associated with Passiflora actinia, Passiflora misera and Passiflora suberosa (Passifloraceae), and build mines on the adaxial leaf surface. Initially the mines are serpentine in shape, but later in larval ontogeny become a blotch type. Although the larvae are hypermetamorphic as in other Gracillariidae, there is no sap-feeding instar in Spinivalva gaucha; the larva feeds on the palisade parenchyma, thus producing granular frass during all instars. Pupation occurs outside the mine; prior to pupating, the larva excretes numerous bubbles that are placed in rows on the lateral margins of the cocoon external surface. This is the second genus of gracillariid moth described for the Atlantic Rain Forest, and the second gracillariid species known to be associated with Passifloraceae.