New insights on the role of paired membrane structures in coronavirus replication.

The replication of coronaviruses, as in other positive-strand RNA viruses, is closely tied to the formation of membrane-bound replicative organelles inside infected cells. The proteins responsible for rearranging cellular membranes to form the organelles are conserved not just among the Coronaviridae family members, but across the order Nidovirales. Taken together, these observations suggest that the coronavirus replicative organelle plays an important role in viral replication, perhaps facilitating the production or protection of viral RNA. However, the exact nature of this role, and the specific contexts under which it is important have not been fully elucidated. Here, we collect and interpret the recent experimental evidence about the role and importance of membrane-bound organelles in coronavirus replication.

Naturaleza, ética, y arquitectura: Autenticidad y criterios éticos que integran el desarrollo de una arquitectura más sostenible = Nature, ethics and architecture: Authenticity and ethics criteria that integrate the development of a more sustainable architecture

La ecología no solamente ha puesto de manifiesto problemas ambientales, sino que ha confirmado la necesidad de una nueva armonía entre los propios seres humanos y de éstos con la naturaleza y con todos los seres que la habitan. Es necesario un nuevo contrato que determine nuestras relaciones con la Naturaleza (Serrs1), y una nueva Ética para nuestras vidas (Guattari2). La ética medioambiental nos ha dado una visión universal y supra-generacional de la gestión de la naturaleza y como consecuencia, una nueva forma de construir nuestra ‘segunda’ Naturaleza, que es la arquitectura. ¿Qué es lo esencial que esta nueva ética exige para la arquitectura? Este es un momento crucial para reconsiderar los objetivos de la arquitectura, porque lo ‘eco’ está produciendo grandes cambios. ¿Implica esta era post-ecológica una particular ética, es decir, referida a sus fines y medios? ¿Porqué, para qué, para quién, cómo debemos hacer la arquitectura de nuestro tiempo? Es momento de afrontar críticamente el discurso de la eco-arquitectura, e incluso de repensar los propios límites de la arquitectura. El desarrollo actual del conocimiento medioambiental es esencialmente técnico y utilitario, pero ¿es el reto solamente técnico?¿Es suficiente la suma de lo medioambiental-social-económico-cultural para definirla? ¿Hay claves que nos puedan dar la dimensión ética de esta aproximación técnica-empírica? ¿Sabemos lo que estamos haciendo cuando aplicamos este conocimiento? Y, sobre todo, ¿cuál es el sentido de lo que estamos haciendo? La tesis que se propone puede resumirse: De acuerdo con el actual conocimiento que tenemos de la Naturaleza, la Arquitectura de nuestro tiempo deber reconsiderar sus fines y medios, puesto que la ética medioambiental está definiendo nuevos objetivos. Para fundamentar y profundizar en esta afirmación la tesis analiza cómo son hoy día las relaciones entre Ética-Naturaleza-Arquitectura (Fig.1), lo que facilitará las claves de cuáles son los criterios éticos (en cuanto a fines y medios) que deben definir la arquitectura del tiempo de la ecología. ABSTRACT Ecology shows us not only environmental problems; it shows that we need a new balance and harmony between individuals, beings, communities and Nature. We need a new contract with Nature according to Serres576, and a new Ethics for our lives according to Guattari577. Environmental ethics have given us a universal and supra-generational vision of the management of our Nature and, as a consequence, a new way to construct our ‘second’ nature, which is architecture. What is essential for this new architecture that the new ethics demand? This is a critical moment to reconsider the object of architecture, because the ‘eco’ is making significant changes in it. Are there any specifically ethical concerns (ends and means) in the post-ecological era? Why, for what, for whom, how should we make architecture in our times? This is the time to approach the eco-architectural discourse critically and to question the current boundaries of architecture itself: Where is eco-architecture going? The current development of environmental knowledge is essentially technical and utilitarian, but it is its technical aspect the only challenge? Is the sum of environmental-social-economic aspects enough to define it? Are there any clues which can give an ethical sense to this technical-empirical approach? Do we know what we are doing when we apply this knowledge? And overall, what is the meaning of what we are doing? Exploring this subject, this thesis makes a statement: In accordance with the actual knowledge of Nature, Architecture of our time must reconsider its ends and means, since the environmental ethics is defining new objectives. To support that, the thesis analyzes what the relationships between Ethics –Nature- Architecture (Fig. 53) are like nowadays, this will provide the clues of which ethical criteria (ends and means) must architecture of an ecological era define.

The impact of mind on nature. Lessons learned from the ecology-aesthetics interplay

The effects of nature on people's mind have been an active research theme for decades. However, the impact of people's mind on landscape ecological health has received less attention. How and why perception, meanings and mental constructs determine the way nature is valued and consequently managed? How this interplay should be? These are in some cases more relevant questions than knowing what particular landscapes are preferred (Carlson 1993). This was the underlying inquiry in the focus group experience held in a natural protected area in La Rioja (Spain). Participants were asked to locate in a map areas representing low/high quality in terms of ecology and aesthetics. Some relevant conclusions for landscape management were derived from the analysis of participant's discourse in terms of ecological aesthetical appreciation and their consideration about how human takes place in nature.

The protection receptor for IgG catabolism is the beta2-microglobulin-containing neonatal intestinal transport receptor.

More than 30 years ago, Brambell published the hypothesis bearing his name [Brambell, F. W. R., Hemmings, W. A. & Morris, 1. C. (1964) Nature (London) 203, 1352-1355] that remains as the cornerstone for thinking on IgG catabolism. To explain the long survival of IgG relative to other plasma proteins and its pattern of increased fractional catabolism with high concentrations of IgG, Brambell postulated specific IgG "protection receptors" (FcRp) that would bind IgG in pinocytic vacuoles and redirect its transport to the circulation; when the FcRp was saturated, the excess unbound IgG then would pass to unrestricted lysosomal catabolism. Brambell subsequently postulated the neonatal gut transport receptor (FcRn) and showed its similar saturable character. FcRn was recently cloned but FcRp has not been identified. Using a genetic knockout that disrupts the FcRn and intestinal IgG transport, we show that this lesion also disrupts the IgG protection receptor, supporting the identity of these two receptors. IgG catabolism was 10-fold faster and IgG levels were correspondingly lower in mutant than in wild-type mice, whereas IgA was the same between groups, demonstrating the specific effects on the IgG system. Disruption of the FcRp in the mutant mice was also shown to abrogate the classical pattern of decreased IgG survival with higher IgC concentration. Finally, studies in normal mice with monomeric antigen-antibody complexes showed differential catabolism in which antigen dissociates in the endosome and passes to the lysosome, whereas the associated antibody is returned to circulation; in mutant mice, differential catabolism was lost and the whole complex cleared at the same accelerated rate as albumin, showing the central role of the FcRp to the differential catabolism mechanism. Thus, the same receptor protein that mediates the function of the FcRn transiently in the neonate is shown to have its functionally dominant expression as the FcRp throughout life, resolving a longstanding mystery of the identity of the receptor for the protection of IgG. This result also identifies an important new member of the class of recycling surface receptors and enables the design of protein adaptations to exploit this mechanism to improve survivals of other therapeutic proteins in vivo.

Synthesis and targeted delivery of an azidothymidine homodinucleotide conferring protection to macrophages against retroviral infection.

The infectivity and replication of human (HIV-1), feline (FIV), and murine (LP-BM5) immunodeficiency viruses are all inhibited by several nucleoside analogues after intracellular conversion to their triphosphorylated derivatives. At the cellular level, the main problems in the use of these drugs concern their limited phosphorylation in some cells (e.g., macrophages) and the cytotoxic side effects of nucleoside analogue triphosphates. To overcome these limitations a new nucleoside analogue homodinucleotide, di(thymidine-3'-azido-2',3'-dideoxy-D-riboside)-5'-5'-p1-p2-pyrophosphat e (AZTp2AZT), was designed and synthesized. AZTp2AZT was a poor in vitro inhibitor of HIV reverse transcriptase, although it showed antiviral and cytotoxic activities comparable to those of the parent AZT when added to cultures of a HTLV-1 transformed cell line. AZTp2AZT encapsulated into erythrocytes was remarkably stable. Induction of erythrocyte-membrane protein clusterization and subsequent phagocytosis of AZTp2AZT-loaded cells allowed the targeted delivery of this impermeant drug to macrophages where its metabolic activation occurs. The addition of AZTp2AZT-loaded erythrocytes to human, feline, and murine macrophages afforded almost complete in vitro protection of these cells from infection by HIVBa-L, FIV, and LP-BM5, respectively. Therefore, AZTp2AZT, unlike the membrane-diffusing azidothymidine, acts as a very efficient antiretroviral prodrug following selective targeting to macrophages by means of loaded erythrocytes.

Pharmacological modulation of heat shock factor 1 by antiinflammatory drugs results in protection against stress-induced cellular damage.

The activation of heat shock genes by diverse forms of environmental and physiological stress has been implicated in a number of human diseases, including ischemic damage, reperfusion injury, infection, neurodegeneration, and inflammation. The enhanced levels of heat shock proteins and molecular chaperones have broad cytoprotective effects against acute lethal exposures to stress. Here, we show that the potent antiinflammatory drug indomethacin activates the DNA-binding activity of human heat shock transcription factor 1 (HSF1). Perhaps relevant to its pharmacological use, indomethacin pretreatment lowers the temperature threshold of HSF1 activation, such that a complete heat shock response can be attained at temperatures that are by themselves insufficient. The synergistic effect of indomethacin and elevated temperature is biologically relevant and results in the protection of cells against exposure to cytotoxic conditions.

The Revision of the Insurance Mediation Rules at EU Level and its Impact on Consumer Protection

The European Commission has put forward a new proposal for a directive on insurance mediation which should provide for significant changes in practices of selling insurance products and guarantee enhanced level of consumer protection. This proposal accompanies other regulatory initiatives in the insurance sector, all of them pursuing three main objectives: firstly, a strengthened insurance supervision with convergent supervisory standards at EU level; secondly, a better risk management of insurance companies; and thirdly a greater protection of policyholders. All these initiatives contribute to the EU programme on consumer protection and herald a new approach to EU insurance regulation and supervision. However, while the new supervisory rules are a direct response to the financial crisis and shortcomings of crossborder cooperation between national supervisors, the plans for the revision of insurance mediation rules were conceived much earlier due to scandals with mis-selling of insurance products in the United States and some EU Member States. This article will focus entirely on the Commission’s initiative in the consumer mediation area and the aspects of insurance supervision and risk management will be dealt with in separate articles.

Patenting Strategies of the EU Pharmaceutical Industry -Crossroad between Patent Law and Competition Policy. Research Papers in Law, 1/2011

From the Introduction. The pharmaceutical sector inquiry carried out by the European Commission in 2008 provides a useful framework for assessing the relationship between the patent system on the one hand and competition policy and law on the other hand. The pharmaceutical market is not only specifically regulated. It is also influenced by the special characteristics of the patent system which enables pharmaceutical companies engaged in research activities to enter into additional arrangements to cope with the competitive pressures of early patent application and the delays in drug approval. Patents appear difficult to reconcile with the need for sufficient and adequate access to medicines, which is why competition expectations imposed on the pharmaceutical sector are very high. The patent system and competition law are interacting components of the market, into which they must both be integrated. This can result in competition law taking a very strict view on the pharmaceutical industry by establishing strict functional performance standards for the reliance on intellectual property rights protection granted by patent law. This is in particular because in this sector the potential welfare losses are not likely to be of only monetary nature. In brief, the more inefficiencies the patent system produces, the greater the risk of an expansive application of competition law in this field. The aim of the present study is to offer a critical and objective view on the use or abuse of patents and defensive strategies in the pharmaceutical industry. It shall also seek to establish whether patents as presently regulated offer an appropriate degree of protection of intellectual property held by the economic operators in the pharmaceutical sector and whether there is a need or, for that matter, scope for improvement. A useful starting point for the present study is provided by the pharmaceutical sector competition inquiry (hereafter “the sector inquiry”) carried out by the European Commission during the first half of 2008. On 8 July 2008, the Commission adopted its Final Report pursuant to Article 17 of Regulation 1/2003 EC, revealing a series of “antitrust shortcomings” that would require further investigation1.

The roadsides of Oregon; a survey.

Report of a study of the problem of roadside improvement along the highways of that state.

Journal of plant protection. (Byochu - Gai Zasshi)

Mode of access: Internet.

Environmental and economic review of crop protection and pesticide use in Ethiopia /

"November 1995."

The Rock River Country : an inventory of the region's resources.

"IDNR/EEA-96/09."--T.p. verso.

The conduct of life, Nature, and other essays

"First published in this edition, 1908; reprinted ... 1919."

The Impact of Chinese Culture on European Landscape Design

The English garden design style and the landscape garden movement became the most emblematic cultural achievement of England in the 18th-19th century. The natural garden style proved to be the symbol of the liberal philosophy and the enlightened way of thinking. But the English landscape garden, which can be seen as an idealized view of nature, is inspired by the classical landscape paintings and is also influenced by the classic Chinese gardens, which had recently been described by European travellers. The interest for Chinese culture, architecture and garden design spread around the British island and inspired the talented garden designers. The gardens of Chambers created a new section in the picturesque landscape gardens, the so called anglo-chinoiseric gardens where eastern, mainly Chinese architectural motives and garden elements have been used in most cases without integrating the Chinese nature philosophy. This first, more or less formal effects of Chinese garden design on European landscape architecture were overwritten by garden designers and horticulturalist during the gardenesque period of the early 19th century when great variety in plant design was taken into the focus of landscape architecture.

Natura 2000 erdők közgazdasági környezetének elemzése (Assessment of the economic environment of Natura 2000 forests)

Ebben a tanulmányban a Natura 2000 erdők közgazdasági kérdéseit jártuk körül az ökoszisztéma-szolgáltatások koncepciójának segítségével, nemzetközi és hazai szakirodalomra építve. Emellett a természetközeli erdőgazdálkodás fogalomkörét, s azon belül a folyamatos erdőborítást szolgáló erdőgazdálkodást vettük alapul. A következőkben néhány összegző megállapítást teszünk, és kijelölünk további kutatási irányokat. _____ This study has been prepared within the LIFEinFORESTS – Improved communication, cooperation and capacity building for preserving biodiversity in Natura 2000 forests (B2 action, LIFE13 INF/HU/001163) – project in the framework of LIFE+ Information and Communication under the contract signed with the Duna-Ipoly National Park Directorate. The main aim of the study is to summarize the international and Hungarian economic and environmental economic literature related to the Natura 2000 forests, and serve as a background study for the communication with and training of forest owners and users operating at Natura 2000 sites. The concept of ecosystem services (ESs) is used as an overall framework for the study. In our opinion it is able to show all the benefits provided by forests and can also help to reveal that the benefits of nature-oriented, continuous cover forest management (CCF) can exceed the benefits of traditional rotation forest management (RFM). The definition and the classification of the Millennium Ecosystem Assessment (MA, 2003, 2005) is used throughout the study, so provisioning, cultural, regulating and supporting services are distinguished.