Design, synthesis, and biological evaluation of new (2E,6E)-10-(dimethylamino)-3,7-dimethyl-2,6-decadien-1-ol ethers as inhibitors of human and Trypanosoma cruzi oxidosqualene cyclase

New dimethylamino truncated squalene ether derivatives containing a different aromatic moiety (phenyl, naphthyl, and biphenyl) or a simple alkyl (n-hexylic) group were synthesized as inhibitors of the oxidosqualene cyclase (OSC) and of the sterol biosynthetic pathway. The activity against human OSC was compared with the activity against the OSCs of pathogenic organisms such as Pneumocystis carinii and Trypanosoma cruzi. The phenyl derivative was the most potent inhibitor of T. cruzi OSC.     

Projection maps of three members of the KdgM outer membrane protein family

We present the projection structures of the three outer membrane porins KdgM and KdgN from Erwinia chrysanthemi and NanC from Escherichia coli, based on 2D electron crystallography. A wide screening of 2D crystallization conditions yielded tubular crystals of a suitable size and quality to perform high-resolution electron microscopy. Data processing of untilted samples allowed us to separate the information of the two crystalline layers and resulted in projection maps to a resolution of up to 7 Å. All three proteins exhibit a similar putative β-barrel structure and the three crystal forms have the same symmetry. However, there are differences in the packing arrangements of the monomers as well as the densities of the projections. To interpret these projections, secondary structure prediction was performed using β-barrel specific prediction algorithms. The predicted transmembrane β-barrels have a high similarity in the arrangement of the putative β-strands and the loops, but do not match those of OmpG, a related protein porin whose structure was solved.     

Relationship between optimal lactate removal power output and Olympic triathlon performance

To investigate the relationships between race performance and parameters at the optimal power output for lactate removal, 10 male triathletes were examined. Exercise intensities for lactate removal were defined by calculating 50% of difference (DeltaT) between running velocity (V(r)) at individual anaerobic threshold (IAT) and at individual ventilatory threshold (IVT), then choosing 3 V(r): at IVT plus 50% DeltaT (IVT(+50%DeltaT)), at IVT, and at IVT minus 50% DeltaT (IVT(-50%DeltaT)). After a 6-minute treadmill run at 75% of difference between IAT and V(.-)O2max, all triathletes performed a 30-minute active recovery run at IVT(+50%DeltaT), IVT, and IVT(-50%DeltaT). Capillary blood lactate was determined at 1, 3, 6, 9, 12, 15, 20, 25, and 30 minutes of recovery. The IVT(-50%DeltaT) recovery was the most efficient V(r) for lactate removal. Running velocities at IVT and IVT(-50%DeltaT) were highly (p < 0.01) related to cycle, run, and overall race time. V(.-)O2max values at IAT, IVT(+50%DeltaT), and IVT were less (p < 0.05) related to split and overall race time. The variable most related to overall race time, as determined by stepwise multiple linear regression analysis, was the V(r) at IVT(-50%DeltaT) (r = 0.87, p = 0.001). The R(2) value of 0.76 indicated that V(r) at IVT(-50%DeltaT) could account for 76% of the variance in triathlon race time. This study shows that the race performances of triathletes are highly related to the V(r) at which the most efficient lactate removal (IVT(-50%DeltaT)) occurs. These findings suggest that the assessment of V(r) at IVT and IAT (from which V(r) at IVT(-50%DeltaT) are calculated) may be a useful method for monitoring training-induced adaptations and performance improvements in athletes who participate in Olympic triathlons.     

Solution structure of ApaG from Xanthomonas axonopodis pv. citri reveals a fibronectin-3 fold

ApaG proteins are found in a wide variety of bacterial genomes but their function is as yet unknown. Some eukaryotic proteins involved in protein-protein interactions, such as the human polymerase delta-interacting protein (PDIP38) and the F Box A (FBA) proteins, contain ApaG homology domains. We have used NMR to determine the solution structure of ApaG protein from the plant pathogen Xanthomonas axonopodis pv. citri (ApaG(Xac)) with the aim to shed some light on its molecular function. ApaG(Xac) is characterized by seven antiparallel beta strands forming two beta sheets, one containing three strands (ABE) and the other four strands (GFCC'). Relaxation measurements indicate that the protein has a quite rigid structure. In spite of the presence of a putative GXGXXG pyrophosphate binding motif ApaG(Xac) does not bind ATP or GTP, in vitro. On the other hand, ApaG(Xac) adopts a fibronectin type III (Fn3) fold, which is consistent with the hypothesis that it is involved in mediating protein-protein interactions. The fact that the proteins of ApaG family do not display significant sequence similarity with the Fn3 domains found in other eukaryotic or bacterial proteins suggests that Fn3 domain may have arisen earlier in evolution than previously estimated.     

PNA conjugated to high-molecular weight poly(ethylene glycol): synthesis and properties

The conjugation of a bioactive, fluorescent PNA sequence to high-molecular weight poly(ethylene glycol) (PEG) is described and the properties of the PEG-PNA conjugate are evaluated.     

Ecological index of maturity to evaluate the vegetation disturbance of areas affected by restoration work: a practical example of its application in an area of the Southern Alps

This paper presents the ecological index of maturity (EIM), a new index for evaluating the vegetation disturbance of an area affected by environmental restoration measures based on the study of plant communities. The EIM is the result of the unification and development of some floristic‐vegetational indices devised by Taffetani and Rismondo (2009) and Rismondo et al. (2011) to assess the ecological functionality of agro‐ecosystems. The EIM provides a value between 0 (high vegetation disturbance) and 9 (undisturbed vegetation), obtained by considering three distinct variables of the species of a plant community: phytosociological class, chorotype, and coverage. Starting from the measure of the degree of maturity of the vegetation (dynamic stage of succession), EIM values tend to decrease the greater the coverage of exotic species and the lower the coverage of endemic species present in the plant community. A practical example, in which the EIM is applied to a mountainous area in the Southern Alps (Northern Italy) that, following a landslide, was subject to soil bioengineering work aimed at slope stabilization and environmental restoration, is provided in order to understand the importance and features of the EIM.     

Toward an Overall Analytical Framework for the Integrated Sustainability Assessment of the Production and Supply of Raw Materials and Primary Energy Carriers

The sustainable production and supply of raw materials (“nonenergy raw materials”) and primary energy carriers (“energy raw materials”) is a core element of many policies. The natural resource base for their production and supply, and the access thereto, are limited. Moreover, raw material supply is high on environmental and social impact agendas as well. A broad, quantitative framework that supports decision makers is recommended so as to make use of raw materials and primary energy carriers more sustainably. First, this article proposes a holistic classification of raw materials and primary energy carriers. This is an essential prerequisite for developing an integrated sustainability assessment framework (ISAF). Indeed, frequently, only a subset of raw materials and primary energy carriers are considered in terms of their source, sector, or final application. Here, 85 raw materials and 30 primary energy carriers overall are identified and grouped into seven and five subgroups, respectively. Next, this article proposes a quantitative ISAF for the production and supply of raw materials and primary energy carriers, covering all the sustainability pillars. With the goal of comprehensiveness, the proposed ISAF integrates sustainability issues that have been covered and modeled in quite different quantitative frameworks: ecosystem services; classical life cycle assessment (LCA); social LCA; resource criticality assessment; and particular international concerns (e.g., conflict minerals assessment). The resulting four areas of concerns (i.e., environmental, technical, economic, and social/societal) are grouped into ten specific sustainability concerns. Finally, these concerns are quantified through 15 indicators, enabling the quantitative sustainability assessment of the production and supply of raw materials and primary energy carriers.     

The cytogenetic architecture of the aphid genome

In recent years aphids, with their well‐defined polyphenism, have become favoured as model organisms for the study of epigenetic processes. The availability of the pea aphid (Acyrthosiphon pisum) genome sequence has engendered much research aimed at elucidating the mechanisms by which the phenotypic plasticity of aphids is inherited and controlled. Yet so far this research effort has paid little attention to the cytogenetic processes that play a vital part in the organisation, expression and inheritance of the aphid genome. Aphids have holocentric chromosomes, which have very different properties from the chromosomes with localised centromeres that are found in most other organisms. Here we review the diverse forms of aphid chromosome behaviour that occur during sex determination and male and female meiosis, often in response to environmental changes and mediated by endocrine factors. Remarkable differences occur, even between related species, that could have significant effects on the inheritance of all or parts of the genome. In relation to this, we review the particular features of the distribution of heterochromatin, rDNA genes and other repetitive DNA in aphid chromosomes, and discuss the part that these may play in the epigenetic modification of chromatin structure and function.     

The Arf GAP CNT-2 regulates the apoptotic fate in C. elegans asymmetric neuroblast divisions

During development, all cells make the decision to live or die. Although the molecular mechanisms that execute the apoptotic program are well defined, less is known about how cells decide whether to live or die. In C.?elegans, this decision is linked to how cells divide asymmetrically [1, 2]. Several classes of molecules are known to regulate asymmetric cell divisions in metazoans, yet these molecules do not appear to control C.?elegans divisions that produce apoptotic cells [3]. We identified CNT-2, an Arf GTPase-activating protein (GAP) of the AGAP family, as a novel regulator of this type of neuroblast division. Loss of CNT-2 alters daughter cell size and causes the apoptotic cell to adopt the fate of its sister cell, resulting in extra neurons. CNT-2's Arf GAP activity is essential for its function in these divisions. The N terminus of CNT-2, which contains?a GTPase-like domain that defines the AGAP class of Arf GAPs, negatively regulates CNT-2's function. We provide evidence that CNT-2 regulates receptor-mediated endocytosis and consider the implications of its role in asymmetric cell divisions.