PARP‐mediated proteasome activation: A co‐ordination of DNA repair and protein degradation?

During the evolution of aerobic life, antioxidant defence systems developed that either directly prevent oxidative modifications of the cellular constituents or remove the modified components. An example of the latter is the proteasome, which removes cytosolic oxidised proteins. Recently, a novel mechanism of activation of the nuclear 20S proteasome was discovered: automodified poly-(ADP-ribose) polymerase-1 (PARP-1) activates the proteasome to facilitate selective degradation of oxidatively damaged histones. Since activation of the PARP-1 itself is induced by DNA damage and is supposed to play a role in DNA repair, these new results suggest a joint role of PARP-1 in the removal of oxidised nucleoproteins and in DNA repair. We hypothesise that PARP-1 could provide a co-ordinative link between two nuclear antioxidant defence systems, whose concerted activation would produce a fast and efficient restoration of the native chromatin structure following oxidative stress.     

Are nociceptin(1‐13)NH2 and its structural analogue [ORN9]nociceptin(1‐13)NH2 able to affect brain antioxidant status in control and kainic acid‐treated rats?

In‐vivo effects of nociceptin (N/OFQ(1‐13)NH₂) on the levels of lipid peroxidation and cell enzyme (superoxide dismutase, glutathione peroxidase and glutathione reductase) and non‐enzyme (glutathione) antioxidants in brain of control and kainic acid‐treated rats were studied. N/OFQ(1‐13)NH₂ effects were compared with those of its structural analogue [Orn⁹]N/OFQ(1‐13)NH₂. Kainic acid (25 µg, i.c.v) increased the lipid peroxidation (4 and 24 h after kainic acid treatment) and decreased the glutathione level (1 h after kainic acid injection). We failed to find, any changes in antioxidant enzyme activities, independently of the time of kainic acid treatment. At the background of kainic acid‐effects, N/OFQ(1‐13)NH₂ and [Orn⁹] N/OFQ(1‐13)NH₂, injected 30 min before kainic acid, had no effects on all parameters, tested in brain. In addition, the neuropeptides did not change the antioxidant status in brain of control animals. It might be concluded that N/OFQ(1‐13)NH₂ and [Orn⁹]N/OFQ(1‐13)NH₂ have neither pro‐ nor anti‐oxidant activity. Copyright © 2009 John Wiley & Sons, Ltd.     

Brief communication: Could Kadanuumuu (KSD‐VP‐1/1) and Lucy (AL 288‐1) have walked together comfortably?

The estimated lower limb length (0.761–0.793 m) of the partial skeleton of Australopithecus afarensis from Woranso‐Mille (KSD‐VP‐1/1) is outside the previously known range for Australopithecus and within the range of modern humans. The lower limb length of KSD‐VP‐1/1 is particularly intriguing when juxtaposed against the lower limb length estimate of the other partial skeleton of A. afarensis, AL 288‐1 (0.525 m). A sample of 36 children (age, >7 years, trochanteric height = 0.56–0.765 m) and 16 adults (trochanteric height = 0.77–1.00 m) walked at their self‐selected slow, preferred, and fast walking velocities, while their oxygen consumption was monitored. Lower limb length and velocity were correlated with slow (P < 0.001, r² = 0.44), preferred (P < 0.001, r² = 0.55), and fast (P < 0.001, r² = 0.69) walking velocity. The relationship between optimal velocity and lower limb length was also determined and lower limb length explained 47% of the variability in optimal velocity. The velocity profile for KSD‐VP‐1/1 (slow = 0.73–0.75 m/s, preferred = 1.08–1.11 m/s, and fast = 1.48–1.54 m/s) is 36–44% higher than that of AL 288‐1 (slow = 0.53 m/s, preferred = 0.78 m/s, and fast = 1.07 m/s). The optimal velocity for AL 288‐1 is 1.04 m/s, whereas that for KSD‐VP‐1/1 is 1.29–1.33 m/s. This degree of lower limb length dimorphism suggests that members of a group would have had to compromise their preferences to walk together or to split into subgroups to walk at their optimal velocity. Am J Phys Anthropol, 2012. © 2012 Wiley Periodicals, Inc.     

Destabilization and stabilization of poly(A) · poly(U) structure by platinum(II) compounds

A methodology for analyzing the intramolecular structural order of the polynucleotide duplex poly(A) · poly(U) has been developed on the basis of molecular biophysics. The combination of circular dichroism spectroscopy and differential scanning calorimetry was shown to be an optimal approach. It ensures the screening of a wide set of substances and interaction conditions and the choice of compound(s) capable of stabilizing the structure and increasing the biological activity of this duplex. The study is aimed at obtaining a new and highly active antiviral drug.     

Comparison Between poly(dG-dC)·poly(dG-dC) and DNA Modified by cis-diamminedichloroplatinum (II): Immunological and Spectroscopic Studies

Abstract

The importance of the base composition and of the conformation of nucleic acids in the reaction with the drug cis-diamminedichloroplatinum(II) has been studied by competition experiments between the drug and several double-stranded polydeoxyribonucleotides. Binding to poly(dG)·poly(dC) is larger than to poly (dG-dC)·poly(dG-dC). There is no preferential binding in the competition between poly(dG-dC) ·poly(dG-dC), poly(dA-dC) ·poly(dG-dT) and poly(dA-dG)·poly(dC-dT). In the competition between poly(dG-dC) ·poly (dG-dC) (B conformation) and poly(dG-br⁵dC) ·poly(dG-br⁵dC) (Z conformation), the drug binds equally well to both polynucleotides. In natural DNA, modification of guanine residues in (GC)_n·(GC)_nsequences by the drug has been revealed by the inhibition of cleavage of these sequences by the restriction enzyme BssHII. By means of antibodies to platinated poly(dG-dC), it is shown that some of the adducts formed in platinated poly(dG-dC) are also formed in platinated pBR322 DNA. The type of adducts recognized by the antibodies is not known. Thin layer chromatography of the products after chemical and enzymatic hydrolysis of platinated poly(dG-dC) suggests that interstrand cross-links are formed. Finally, the conformations of poly(dG-m⁵dC) modified either by cis-diamminedichloroplatinum(II) or by trans-diammine- dichloroplatinum(II) have been compared by circular dichroism. Both the cis-isomer and the trans-isomer stabilize the Z conformation when they bind to poly(dG-m⁵dC) in the Z conformation. When they bind to poly(dG-m⁵dC) in the B conformation, the conformations of poly(dG-m⁵dC) modified by the cis or the trans-isomer are different. Moreover, the cis-isomer facilitates the B form-Z form transition of the unplatinated regions while the trans-isomer makes it more difficult.     

Are the spatio‐temporal dynamics of soil‐feeding termite colonies shaped by intra‐specific competition?

1. Soil‐feeding termites are abundant and diversified in neotropical forests, where they are among the major decomposers of the soil macrofauna. While niche specialisation along the humification gradient may reduce inter‐specific competition, some species are represented by numerous colonies likely to be involved in intra‐specific competition, but the subterranean nesting habits of most species of soil‐feeding termites make direct observations difficult. 2. The soldierless species Anoplotermes banksi Emerson was studied, which, unlike other Anoplotermes‐group species, builds arboreal nests that can be easily detected. To infer the biological processes driving the spatial distribution of this species, we conducted a 3‐year survey of the dynamics of colonisation of a 1‐ha plot by A. banksi. Ripley's L‐function, detecting aggregation or dispersion at various spatial scales, was used to investigate the distribution pattern of A. banksi nests, as well as the distribution of new and established nests. 3. Only one‐fourth of the nests recorded the first year were still alive after 3 years, highlighting a rapid turnover of the A. banksi nest population. Age classes were differentially affected by mortality, which was higher in young nests than in large, established nests. 4. Established nests were overdispersed at a short range, whereas young nests had a random or clumped distribution. Young nests tended to be overdispersed from established ones and were more abundant in areas with recently dead nests. Dead nests predominantly occurred where A. banksi nests were particularly abundant. Altogether, the present results indicate a negative interaction between neighbouring colonies suggesting intra‐specific competition.     

Are reward polymorphisms subject to frequency‐ and density‐dependent selection? Evidence from a monoecious species pollinated by deceit

Abstract Most deceit‐pollinated species involve floral dimorphisms characterized by the presence of rewarding male flowers and nonrewarding female flowers. It has been proposed that this polymorphism establishes the conditions for the action of frequency dependent selection (FDS). The tendency of foraging animals to aggregate in areas of high resource density suggests that pollination efficiency and fruit production may be positively influenced by flower density (density dependent selection, DDS). In this paper we offer a graphical model describing the effects of FDS and DDS on a monoecious species pollinated by deceit. We test the FDS and DDS assumptions and the predictions of the model using field observations and experimental populations of Begonia gracilis in which population sex ratio and flower density were controlled. We found a marked effect of both FDS and DDS on pollinator visitation, fruit‐set, and on the probability of female flowers to setting fruits. We conclude that these two types of selection have had a strong influence on the evolution of deceit‐pollinated species.     

Are auxin and calcium movements in corn coleoptiles linked processes?

In this paper we present evidence for a tight linkage of calcium and auxin fluxes in corn coleoptile tissue. Imposed lateral gradients of auxin concentration induce a movement of calcium ions to the side of lower auxin concentration in the tissue. Imposing a lateral gradient of calcium concentration in turn leads to a movement of auxin to the side of lower calcium concentration. Whether these fluxes are using symplastic or apoplastic pathways or are transcellular cannot be decided from the results.Countercurrent fluxes of calcium ions and auxin could be demonstrated in polar transport experiments. This might be a further indication of a complex carrier system in the plasma membrane extruding auxin out of the cell with a concomitant calcium influx from the cell wall space into the cytoplasm.     

Are nutrient availability and acidity‐alkalinity gradients related in Sphagnum‐dominated peatlands?

Abstract. Gradients in acidity‐alkalinity and nutrient availability were studied in 2 Sphagnum‐dominated peatlands on the southeastern Italian Alps. Decreasing concentrations of most mineral elements (Ca²⁺, Mg²⁺, Mn²⁺, Al³⁺ and Si⁴⁺) in pore water indicated a progressively lower influx of mineral‐soil water from the slightly minerotrophic conditions in the peatland margins to ombrogenous conditions in the central part of the peatlands. This was paralleled by decreasing concentrations of ash, bulk density, Ca, Fe and, partly, Mn in the peat. The nutrient gradient, as defined by pore water concentrations of N and P, was largely independent of the acidity‐ alkalinity gradient: NO^3‐ and PO₄^3‐ had similar concentrations throughout the gradient, whereas NH₄⁺ concentrations increased with increasing pore‐water pH. In contrast, the peat nutrient gradient coincided with the acidity‐alkalinity gradient, with total concentrations of N and P decreasing from the margin to the centre. Bryophytes and vascular plants had different responses along the acidity‐alkalinity gradient and the nutrient gradient. Bryophyte distribution reflected the acidity‐alkalinity gradient both in pore water and in peat. Vascular plant distribution was mainly influenced by variations in nutrient availability.     

The nature of different influence of Cd<Superscript>2+</Superscript> ions on the conformational equilibrium of triple-stranded polyribonucleotides poly(U)•poly(A)•poly(U) and poly(I)•poly(A)•poly(I) in aqueous solutions

The influence of Cd²⁺ ions on the conformational equilibrium of single-stranded (poly(U), poly(A), poly(I)) and triple-stranded polyribonucleotides (A2I, A2U) in aqueous solutions (0.1 M Na⁺ pH 7) has been investigated using difference UV spectroscopy and thermal denaturation. Analysis of the shape and intensity of the DUV spectra of poly(A), poly(I), and A2I has revealed the presence of two types of complex formed as a result of (i) interaction between Cd²⁺ and the N7 atoms of purines, producing macrochelates; and (ii) binding of Cd²⁺ to the N1 atoms of poly(A) and poly(I). Since Cd²⁺ ions are not bound to heteroatoms of the bases in A2U, the conformation of the structure remains stable up to 0.02 M Cd²⁺. There is a critical Cd²⁺ concentration (～1.5?10^?4 M) above which A2I assumes a new helical conformation with lower thermal stability. It is supposed that, upon the formation of the “metallized” A2I triplex, the Cd²⁺ ions are located inside the triple helix and form bridges between the hypoxanthine and adenine of the homopolynucleotide strands.     

LRRK2 directing ER‐to‐Golgi transport? (ER)yES!

Mutations in leucine‐rich repeat kinase 2 (LRRK2) represent the most frequent genetic lesions associated with Parkinson's disease (PD). LRRK2 function and the pathogenic mechanisms of LRRK2 genetic mutations remain poorly understood. Cho et al report in this issue of The EMBO Journal a new interaction between LRRK2 and the ER exit site (ERES) protein Sec16A, important for anterograde transport of secretory proteins. Moreover, a disease‐associated mutation disrupts LRRK2–Sec16A interaction and ERES function.     

Helix-helix transitions in DNA: fibre X-ray study of the particular cases poly(dG-dC) · poly(dG-dC) and poly(dA) · 2poly(dT)

The helix-helix transitions which occur in poly(dG-dC) · poly(dG-dC) and in poly (dG-m⁵dC) · poly(dG-m⁵dC) are commonly assumed to be changes between the right-handed A- or B-DNA double helices and the left-handed Z-DNA structure. The mechanisms for such transconformations are highly improbable, especially when they are supposed to be active in long polynucleotide chains organised in semicrystalline fibres. The present alternative possibility assumes that rather than the Z-DNA it is a right-handed double helix (S-DNA) which actually takes part in these form transitions. Two molecular models of this S form, in good agreement with X-ray measurements, are proposed. They present alternating C(2′)-endo and C(3′)-endo sugar puckering like the “alternating B-DNA” put forward some years ago. Dihedral angles, sets of atomic coordinates and stereo views of the two S-DNA structures are given, together with curves of calculated diffracted intensities. Furthermore, we question the possibility of obtaining semicrystalline fibres with triple helices of poly(dA) · 2poly(dT) in a way which renders X-ray diffraction efficient. It is suggested that, up to now, only double helices of poly(dA) · poly(dT) can actually be observed by fibre X-ray diffraction measurements. Received: 30 March 1999 / Revised version: 30 June 1999 / Accepted: 30 June 1999     

Are open‐Label Placebos Ethical? Informed Consent and Ethical Equivocations

The doctor‐patient relationship is built on an implicit covenant of trust, yet it was not until the post‐World War Two era that respect for patient autonomy emerged as an article of mainstream medical ethics. Unlike their medical forebears, physicians today are expected to furnish patients with adequate information about diagnoses, prognoses and treatments. Against these dicta there has been ongoing debate over whether placebos pose a threat to patient autonomy. A key premise underlying medical ethics discussion is the notion that the placebo effect necessitates patient deception. Indeed, the American Medical Association guidelines imply that placebo treatment necessary entails a form of deception. As a consequence of this assumption, the fulcrum of debate on the use of placebo treatment has hinged on whether that deception is ever justified. Recently performed experiments with open‐label transparently prescribed placebos have begun to challenge the notion that deception is necessary in eliciting the placebo effect and such effects necessarily involve a binary distinction between autonomy and beneficence. In this article we focus on the content of disclosures in distinctive open‐label, transparently disclosed placebo studies and inquire whether they might be said to invoke deception in clinical contexts, and if so, whether the deception is unethical. We find that open placebos may be said to involve equivocation over how placebos work. However, drawing on surveys of patient attitudes we suggest that this equivocation appears to be acceptable to patients. We conclude that open placebos fulfil current American Medical Association guidelines for placebo use, and propose future research directions for harnessing the placebo effect ethically.     

Are fecundity and longevity of female Aphelinus abdominalis affected by development in GNA‐dosed Macrosiphum euphorbiae?

Abstract. Snowdrop lectin ( Galanthus nivalis agglutinin, GNA) confers partial resistance to several aphid species when incorporated into an artificial diet and/or expressed in transgenic potato. First-tier laboratory-scale experiments were conducted to assess the potential effect of GNA on the longevity and fecundity of female parasitoid Aphelinus abdominalis (Dalman) that had developed in Macrosiphum euphorbiae (Thomas) fed artificial diet containing 0.1% GNA (w/v). In a previous study it was shown that GNA ingested by A. abdominalis larvae is not acutely toxic. It was also shown that GNA has a host-size mediated effect on parasitoid sex ratio and larval development, but no apparent direct effect.         In this study, we report that A. abdominalis larvae that developed in GNA-dosed aphids that were smaller than control aphids of the same age, produced smaller adults with a reduced longevity and fecundity. Aphelinus abdominalis larvae that developed in GNA-dosed aphids older than the control but of the same size, produced adults of similar size that lived as long as the control but had a reduced fecundity.         Our results suggest that GNA fed to aphids in artificial diet has both a host-mediated effect (via aphid-size) and a direct effect on adult parasitoid fecundity. It is not known how GNA affects parasitoid larval development and subsequently adult fecundity, but it is hypothesized that GNA acted as an antifeedant to parasitoid larvae, thus disturbing nutrient assimilation and conversion necessary for egg maturation.     

Synthesis of poly(lactide-co-glycolide-co-ε-caprolactone)-graft-mannosylated poly(ethylene oxide) copolymers by combination of clip and click chemistries

Poly(lactide-co-glycolide) (PLGA) is extensively used in pharmaceutical applications, for example, in targeted drug delivery, because of biocompatibility and degradation rate, which is easily tuned by the copolymer composition. Nevertheless, synthesis of sugar-labeled amphiphilic copolymers with a PLGA backbone is quite a challenge because of high sensitivity to hydrolytic degradation. This Article reports on the synthesis of a new amphiphilic copolymer of PLGA grafted by mannosylated poly(ethylene oxide) (PEO). A novel building block, that is, α-methoxy-ω-alkyne PEO-clip-N-hydroxysuccinimide (NHS) ester, was prepared on purpose by photoreaction of a diazirine containing molecular clip. This PEO block was mannosylated by reaction of the NHS ester groups with an aminated sugar, that is, 2-aminoethyl-α-d-mannopyroside. Then, the alkyne ω-end-group of PEO was involved in a copper alkyne- azide coupling (CuAAC) with the pendent azides of the aliphatic copolyester. The targeted mannose-labeled poly(lactide-co-glycolide-co-ε-caprolactone)-graft-poly(ethylene oxide) copolymer was accordingly formed. Copolymerization of d,l-lactide and glycolide with α-chloro-ε-caprolactone, followed by substitution of chlorides by azides provided the azido-functional PLGA backbone. Finally, micelles of the amphiphilic mannosylated graft copolymer were prepared in water, and their interaction with Concanavalin A (ConA), a glyco-receptor protein, was studied by quartz crystal microbalance. This study concluded to the prospect of using this novel bioconjugate in targeted drug delivery.     

Are Assemblages of Aquatic‐Breeding Anurans (Amphibia) Niches Structured or Neutral?

Local niche‐based processes and dispersal are important determinants of assemblage composition and species diversity. However, there is no consensus about the relative importance of niche and spatial processes to explain the distribution of anuran species in tropical systems. In our study, we analyzed the niche and neutral effects on anuran assemblages and found that biotic interactions were a predictor of assemblage structure. The Eltonian concept of niche was the best predictor for the structure of aquatic‐breeding anuran assemblages, as species tended to co‐occur more often than would be expected by chance. We suggest that the lack of environmental effect could be explained by differences in the pattern of movement between arboreal and non‐arboreal anurans. Once there is a reduction in the number of arboreal anurans in open areas, the importance of habitat heterogeneity to explain assemblage composition should decrease. The lack of correlation between the spatial component in our model and species composition is evidence that spatial processes, such as migration, did not play a major role in structuring local assemblages. Anurans are generally assumed as having poor dispersal ability, yet this assumption is not true for all anuran species. We suggest that future studies should include key behavioral traits, such as site fidelity and homing behavior, as these traits can represent the dispersal abilities of anurans and dispersal ability seems to be important when we try to predict patterns of anuran distribution.