314 research outputs found
Sites within the complement C3b/C4b receptor important for the specificity of ligand binding.
Sustainability, Globalization, and the Energy Sector Europe in a Global Perspective
International audienceThis paper analyzes the socio-economic effects of energy sustainability challenges raised by oil depletion and climate change at the European and global level. We assess macroeconomic impacts at different time horizons over 2010-2100 and under different visions of the future of globalization . Fragmented capital markets affect the pace and direction of change and induce additional economic losses in the long term. Regionalized good markets have a positive effect in the long term since less intense international trade moderates the effects of fossil fuel constraints. A sustainable energy future will require implementing policies and measures that are able to (i) provide correct incentives for long-term investments by resorting to other signals than current market prices, (ii) incorporate sectoral measures that act complementarily to pricing schemes measures for sectors confronted with biased agentsâ behaviors or strong inertias, (iii) foster globalization patterns that are consistent with energy sustainability objectives. The challenge consists in articulating the objectives and the instruments of these different policy and measures triggering the transition towards sustainable future
Global characterization and target identification of piRNAs and endo-siRNAs in mouse gametes and zygotes
44 p.-1 tab.-10 fig.A set of small RNAs known as rasRNAs (repeat-associated small RNAs) have been related to the down-regulation of Transposable Elements (TEs) to safeguard genome integrity. Two key members of the rasRNAs group are piRNAs and endo-siRNAs. We have performed a comparative analysis of piRNAs and endo-siRNAs present in mouse oocytes, spermatozoa and zygotes, identified by deep sequencing and bioinformatic analysis. The detection of piRNAs and endo-siRNAs in the spermatozoa and revealed also in zygotes, hints to their potential delivery to oocytes during fertilization. However, a comparative assessment of the three cell types indicates that both piRNAs and endo-siRNAs are mainly maternally inherited. Finally, we have assessed the role of the different rasRNA molecules in connection with amplification processes by way of the "ping-pong cycle". Our results suggest that the ping-pong cycle can act on other rasRNAs, such as tRNA- and rRNA-derived fragments, thus not only being restricted to TEs during gametogenesis. © 2014 Elsevier B.V.This work was funded by grants from The European Chemical Industry Council Long-range Research Initiative (CEFIC-LRi), from the MEDDTL (11-MRESPNRPE-9-CVS-072), France, from the CSIC (PIE 201020E016), Spain.Peer reviewe
Selection against spermatozoa with fragmented DNA after postovulatory mating depends on the type of damage
<p>Abstract</p> <p>Background</p> <p>Before ovulation, sperm-oviduct interaction mechanisms may act as checkpoint for the selection of fertilizing spermatozoa in mammals. Postovulatory mating does not allow the sperm to attach to the oviduct, and spermatozoa may only undergo some selection processes during the transport through the female reproductive tract and/or during the zona pellucida (ZP) binding/penetration.</p> <p>Methods</p> <p>We have induced DNA damage in spermatozoa by two treatments, (a) a scrotal heat treatment (42 degrees C, 30 min) and (b) irradiation with 137Cs gamma-rays (4 Gy, 1.25 Gy/min). The effects of the treatments were analyzed 21-25 days post heat stress or gamma-radiation. Postovulatory females mated either with treated or control males were sacrificed at Day 14 of pregnancy, and numbers of fetuses and resorptions were recorded.</p> <p>Results</p> <p>Both treatments decreased significantly implantation rates however, the proportion of fetuses/resorptions was only reduced in those females mated to males exposed to radiation, indicating a selection favoring fertilization of sperm with unfragmented DNA on the heat treatment group. To determine if DNA integrity is one of the keys of spermatozoa selection after postovulatory mating, we analyzed sperm DNA fragmentation by COMET assay in: a) sperm recovered from mouse epididymides; b) sperm recovered from three different regions of female uterine horns after mating; and c) sperm attached to the ZP after in vitro fertilization (IVF). Similar results were found for control and both treatments, COMET values decreased significantly during the transit from the uterine section close to the uterotubal junction to the oviduct, and in the spermatozoa attached to ZP. However, fertilization by IVF and intracytoplasmatic sperm injection (ICSI) showed that during sperm ZP-penetration, a stringent selection against fragmented-DNA sperm is carried out when the damage was induced by heat stress, but not when DNA fragmentation was induced by radiation.</p> <p>Conclusion</p> <p>Our results indicate that in postovulatory mating there is a preliminary general selection mechanism against spermatozoa with low motility and fragmented-DNA during the transport through the female reproductive tract and in the ZP binding, but the ability of the ZP to prevent fertilization by fragmented-DNA spermatozoa is achieved during sperm-ZP penetration, and depends on the source of damage.</p
Estimation of interdomain flexibility of N-terminus of factor H using residual dipolar couplings
Characterization of segmental flexibility is needed to understand the biological mechanisms of the very large category of functionally diverse proteins, exemplified by the regulators of complement activation, that consist of numerous compact modules or domains linked by short, potentially flexible, sequences of amino acid residues. The use of NMR-derived residual dipolar couplings (RDCs), in magnetically aligned media, to evaluate interdomain motion is established but only for two-domain proteins. We focused on the three N-terminal domains (called CCPs or SCRs) of the important complement regulator, human factor H (i.e. FH1-3). These domains cooperate to facilitate cleavage of the key complement activation-specific protein fragment, C3b, forming iC3b that no longer participates in the complement cascade. We refined a three-dimensional solution structure of recombinant FH1-3 based on nuclear Overhauser effects and RDCs. We then employed a rudimentary series of RDC datasets, collected in media containing magnetically aligned bicelles (disk-like particles formed from phospholipids) under three different conditions, to estimate interdomain motions. This circumvents a requirement of previous approaches for technically difficult collection of five independent RDC datasets. More than 80% of conformers of this predominantly extended three-domain molecule exhibit flexions of < 40 °. Such segmental flexibility (together with the local dynamics of the hypervariable loop within domain 3), could facilitate recognition of C3b via initial anchoring and eventual reorganization of modules to the conformation captured in the previously solved crystal structure of a C3b:FH1-4 complex
Chapter 6 - Assessing transformation pathways
Stabilizing greenhouse gas (GHG) concentrations at any level will require deep reductions in GHG emissions. Net global CO2 emissions, in particular, must eventually be brought to or below zero. Emissions reductions of this magnitude will require large-scale transformations in human societies, from the way that we produce and consume energy to how we use the land surface. The more ambitious the stabilization goal, the more rapid this transformation must occur. A natural question in this context is what will be the transformation pathway toward stabilization; that is, how do we get from here to there?
The topic of this chapter is transformation pathways. The chapter is motivated primarily by three questions. First, what are the near-term and future choices that define transformation pathways including, for example, the goal itself, the emissions pathway to the goal, the technologies used for and sectors contributing to mitigation, the nature of international coordination, and mitigation policies? Second, what are the key decision making outcomes of different transformation pathways, including the magnitude and international distribution of economic costs and the implications for other policy objectives such as those associated with sustainable development? Third, how will actions taken today influence the options that might be available in the future?
Two concepts are particularly important for framing any answers to these questions. The first is that there is no single pathway to stabilization of GHG concentrations at any level. Instead, the literature elucidates a wide range of transformation pathways. Choices will govern which pathway is followed. These choices include, among other things, the long-term stabilization goal, the emissions pathway to meet that goal, the degree to which concentrations might temporarily overshoot the goal, the technologies that will be deployed to reduce emissions, the degree to which mitigation is coordinated across countries, the policy approaches used to achieve these goals within and across countries, the treatment of land use, and the manner in which mitigation is meshed with other policy objectives such as sustainable development.
The second concept is that transformation pathways can be distinguished from one another in important ways. Weighing the characteristics of different pathways is the way in which deliberative decisions about transformation pathways would be made. Although measures of aggregate economic implications have often been put forward as key deliberative decision making factors, these are far from the only characteristics that matter for making good decisions. Transformation pathways inherently involve a range of tradeoffs that link to other national and policy objectives such as energy and food security, the distribution of economic costs, local air pollution, other environmental factors associated with different technology solutions (e.g., nuclear power, coal-fired carbon dioxide capture and storage (CCS)), and economic competitiveness. Many of these fall under the umbrella of sustainable development.
A question that is often raised about particular stabilization goals and transformation pathways to those goals is whether the goals or pathways are "feasible". In many circumstances, there are clear physical constraints that can render particular long-term goals physically impossible. For example, if additinional mitigation beyond that of today is delayed to a large enough degree and carbon dioxide removal (CDR) options are not available (see Section 6.9), a goal of reaching 450 ppm CO2eq by the end of the 21st century can be physically impossible. However, in many cases, statements about feasibility are bound up in subjective assessments of the degree to which other characteristics of particular transformation pathways might influence the ability or desire of human societies to follow them. Important characteristics include economic implications, social acceptance of new technologies that underpin particular transformation pathways, the rapidity at which social and technological systems would need to change to follow particular pathways, political feasibility, and linkages to other national objectives. A primary goal of this chapter is to illuminate these characteristics of transformation pathways
Variability and Action Mechanism of a Family of Anticomplement Proteins in Ixodes ricinus
Background: Ticks are blood feeding arachnids that characteristically take a long blood meal. They must therefore counteract host defence mechanisms such as hemostasis, inflammation and the immune response. This is achieved by expressing batteries of salivary proteins coded by multigene families. Methodology/Principal Findings: We report the in-depth analysis of a tick multigene family and describe five new anticomplement proteins in ixodes ricinus. Compared to previously described Ixodes anticomplement proteins, these segregated into a new phylogenetic group or subfamily. These proteins have a novel action mechanism as they specifically bind to properdin, leading to the inhibition of C3 convertase and the alternative complement pathway. An excess of non-synonymous over synonymous changes indicated that coding sequences had undergone diversifying selection. Diversification was not associated with structural, biochemical o, functional diversity, adaptation to host species or stage specificity but rather to differences in antigenicity. Conclusion/Significance: Anticomplement proteins from I. ricinus are the first inhibitors that specifically target a positive regulator of complement, properdin. They may provide new tools for the investigation of role of properdin in physiological and pathophysiological mechanisms. They may also be useful in disorders affecting the alternative complement pathway, Looking for and detecting the different selection pressures involved will help in understanding the evolution of multigene families and hematophagy in arthropods. © 2008 Couveur et al.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe
Friends and Foes from an Ant Brain's Point of View â Neuronal Correlates of Colony Odors in a Social Insect
Background: Successful cooperation depends on reliable identification of friends and foes. Social insects discriminate colony members (nestmates/friends) from foreign workers (non-nestmates/foes) by colony-specific, multi-component colony odors. Traditionally, complex processing in the brain has been regarded as crucial for colony recognition. Odor information is represented as spatial patterns of activity and processed in the primary olfactory neuropile, the antennal lobe (AL) of insects, which is analogous to the vertebrate olfactory bulb. Correlative evidence indicates that the spatial activity patterns reflect odor-quality, i.e., how an odor is perceived. For colony odors, alternatively, a sensory filter in the peripheral nervous system was suggested, causing specific anosmia to nestmate colony odors. Here, we investigate neuronal correlates of colony odors in the brain of a social insect to directly test whether they are anosmic to nestmate colony odors and whether spatial activity patterns in the AL can predict how odor qualities like ââfriendââ and ââfoeââ are attributed to colony odors. Methodology/Principal Findings: Using ant dummies that mimic natural conditions, we presented colony odors and investigated their neuronal representation in the ant Camponotus floridanus. Nestmate and non-nestmate colony odors elicited neuronal activity: In the periphery, we recorded sensory responses of olfactory receptor neurons (electroantennography), and in the brain, we measured colony odor specific spatial activity patterns in the AL (calcium imaging). Surprisingly, upon repeated stimulation with the same colony odor, spatial activity patterns were variable, and as variable as activity patterns elicited by different colony odors. Conclusions: Ants are not anosmic to nestmate colony odors. However, spatial activity patterns in the AL alone do not provide sufficient information for colony odor discrimination and this finding challenges the current notion of how odor quality is coded. Our result illustrates the enormous challenge for the nervous system to classify multi-component odors and indicates that other neuronal parameters, e.g., precise timing of neuronal activity, are likely necessary for attribution of odor quality to multi-component odors
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