Logistics and mobility policies for sustainable development and regional integration: conceptual framework and regional experiences

This FAL Bulletin summarizes the main findings and proposals contained in the document “Políticas de logística y movilidad para el desarrollo sostenible y la integración regional”, recently published by the Natural Resources and Infrastructure Division (NRID), ECLAC. It contains a proposal for a paradigm shift in the formulation of national logistics and mobility policies, with common guidelines for Latin American and Caribbean countries.

The urochloa foliar blight and collar rot pathogen rhizoctonia solani AG-1 IA emerged in South America via a host shift from rice

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Studying Electrophoretic Separations Using Cholate Micelles: Effects Of Ph, Temperature, And Composition

Micelle-forming bile salts have previously been shown to be effective pseudo-stationary phases for separating the chiral isomers of binaphthyl compounds with micellar electrokinetic capillary chromatography (MEKC). Here, cholate micelles are systematically investigated via electrophoretic separations and NMR using R, S-1, 1¿- binaphthyl- 2, 2¿-diylhydrogenphosphate (BNDHP) as a model chiral analyte. The pH, temperature, and concentration of BNDHP were systematically varied while monitoring the chiral resolution obtained with MEKC and the chemical shift of various protons in NMR. NMR data for each proton on BNDHP is monitored as a function of cholate concentration: as cholate monomers begin to aggregate and the analyte molecules begin to sample the micelle aggregate we observe changes in the cholate methyl and S-BNDHP proton chemical shifts. From such NMR data, the apparent CMC of cholate at pH 12 is found to be about 13-14 mM, but this value decreases at higher pH, suggesting that more extreme pHs may give rise to more effective separations. In general, CMCs increase with temperature indicating that one may be able to obtain better separations at lower temperatures. S-BNDHP concentrations ranging from 50 ¿M to 400 ¿M (pH 12.8) gave rise to apparent cholate CMC values from 10 mM to 8 mM, respectively, indicating that S-BNDHP, the chiral analyte molecule, may play an active role in stabilizing cholate aggregates. In all, these data show that NMR can be used to systematically investigate a complex multi-variable landscape of potential optimizations of chiral separations.

Modeling of electroosmotic and electrophoretic mobilization in capillary and microchip isoelectric focusing

Our dynamic capillary electrophoresis model which uses material specific input data for estimation of electroosmosis was applied to investigate fundamental aspects of isoelectric focusing (IEF) in capillaries or microchannels made from bare fused-silica (FS), FS coated with a sulfonated polymer, polymethylmethacrylate (PMMA) and poly(dimethylsiloxane) (PDMS). Input data were generated via determination of the electroosmotic flow (EOF) using buffers with varying pH and ionic strength. Two models are distinguished, one that neglects changes of ionic strength and one that includes the dependence between electroosmotic mobility and ionic strength. For each configuration, the models provide insight into the magnitude and dynamics of electroosmosis. The contribution of each electrophoretic zone to the net EOF is thereby visualized and the amount of EOF required for the detection of the zone structures at a particular location along the capillary, including at its end for MS detection, is predicted. For bare FS, PDMS and PMMA, simulations reveal that EOF is decreasing with time and that the entire IEF process is characterized by the asymptotic formation of a stationary steady-state zone configuration in which electrophoretic transport and electroosmotic zone displacement are opposite and of equal magnitude. The location of immobilization of the boundary between anolyte and most acidic carrier ampholyte is dependent on EOF, i.e. capillary material and anolyte. Overall time intervals for reaching this state in microchannels produced by PDMS and PMMA are predicted to be similar and about twice as long compared to uncoated FS. Additional mobilization for the detection of the entire pH gradient at the capillary end is required. Using concomitant electrophoretic mobilization with an acid as coanion in the catholyte is shown to provide sufficient additional cathodic transport for that purpose. FS capillaries dynamically double coated with polybrene and poly(vinylsulfonate) are predicted to provide sufficient electroosmotic pumping for detection of the entire IEF gradient at the cathodic column end.

Regulation of human liver delta-aminolevulinic acid synthase by bile acids

Aminolevulinic acid synthase 1 (ALAS1) is the rate-limiting enzyme of heme synthesis in the liver and is highly regulated to adapt to the metabolic demand of the hepatocyte. In the present study, we describe human hepatic ALAS1 as a new direct target of the bile acid-activated nuclear receptor farnesoid X receptor (FXR). Experiments in primary human hepatocytes and in human liver slices showed that ALAS1 messenger RNA (mRNA) and activity is increased upon exposure to chenodeoxycholic acid (CDCA), the most potent natural FXR ligand, or the synthetic FXR-specific agonist GW4064. Moreover, overexpression of a constitutively active form of FXR further increased ALAS1 mRNA expression. In agreement with these observations, an FXR response element was identified in the 5' flanking region of human ALAS1 and characterized in reporter gene assays. A highly conserved FXR binding site (IR1) within a 175-bp fragment at -13 kilobases upstream of the transcriptional start site was able to trigger an FXR-specific increase in luciferase activity upon CDCA treatment. Site-directed mutagenesis of IR1 abolished this effect. Binding of FXR/retinoid acid X receptor heterodimers was demonstrated by mobility gel shift experiments. Conclusion: These data strongly support a role of bile acid-activated FXR in the regulation of human ALAS1 and, consequently, hepatic porphyrin and heme synthesis. These data also suggest that elevated endogenous bile acids may precipitate neuropsychiatric attacks in patients with acute hepatic porphyrias.

High-resolution computer simulation of electrophoretic mobilization in isoelectric focusing

Cationic and anionic electrophoretic mobilization for focusing of hemoglobins (Hb's) in the presence of 100 carrier ampholytes covering a pI range of 6.00-7.98 was studied by computer simulation at a constant current density of 300 A/m(2). Electropherograms that would be produced by whole column imaging and by single detectors placed at different locations along the focusing column are presented. Upon mobilization, peak heights of the Hb zones decrease, but the zones retain a relatively sharp constant profile and are migrating at a constant velocity. A further peak decrease occurs during readjustment at the locations of the original buffer/column interfaces, indicating that detection sensitivity is the lowest at these locations. An anionic carrier ampholyte mobility smaller than that of its cationic species produces a cathodic drift which is smaller than the transport rate used for electrophoretic mobilization. Compared to the case with equal mobilities of carrier ampholyte species, a small increase (decrease) is predicted for the cationic (anionic) mobilization rate within the focusing column. Simulation data suggest that electrophoretic mobilization after focusing and focusing with concurrent electrophoretic mobilization are comparable isotachophoretic processes that occur when there is an uninterrupted flux of an ion through the focusing column. Cathodic drift caused by unequal mobilities of the species of carrier ampholytes, electrophoretic mobilization, and decomposition occurring at the pH gradient edges are related electrophoretic processes.

The Use of New Technology and Occupational Mobility: An Event History Analysis of the Swiss Labor Market

The investigation of the consequences of new technologies has a long standing tradition within economics. Particularly, labor economists are wondering how the introduction of new technologies, e.g. Personal Computers, have shaped labor markets. Former research has concentrated on the question of whether on-the-job use of PCs creates a wage bonus for employees. In this paper, we investigate whether the use of PCs increases employees’ probability of an upward shift in their employment status and whether it reduces the risk of involuntary labor market exits. We do so by applying event history analysis to the Swiss Labor Market Survey, a random sample of 3028 respondents, and by analyzing a Panel sub-sample of 650 respondents conducted recently in Switzerland. Our results show that on-the-job use of PCs was beneficial for employees in the past by increasing their probability of an upward shift by approximately 50%. The analysis also suggests that PC use reduces the risk and duration of unemployment. However, these latter results fail to reach statistical significance.

Rebalancing urban mobility: a tale of four cities

The key of mobility in urban planning is not in dispute. Integrated strategies that take into account the interrelations among land use, transport supply and demand and the different transportation modes are more necessary than ever. In Europe, regulatory tools such as local mobility plans or traffic plans have been enforced for a long time, evolving into so-called sustainable urban transport plans (SUTP) ? that is, plans thatmerge urban planning,mobility governance, social awareness and environmental safeguards to develop a vision based on sustainability and equity. Indeed, SUTP are aimed at solving typical problems in current land use, such as urban sprawl, which make clear the need for a paradigm shift from transport (or mobility) planning to land use (or city) planning, thereby producing urban mobility plans that are fully aligned with integrated urban development plans. This paper describes how SUTP are articulated across Europe according to four case studies: Peterborough (UK), Chambe¿ry (France), Ferrara (Italy) and Pinto (Spain), to highlight variations and commonalities, both among the four national legal frameworks and the actual planning processes at the local level. Objectives, measures and indicators used in the monitoring and evaluation phases have been analysed and the results assessed. The main conclusion of the paper is that, as seen in these real-life examples, the lack of integration between spatial planning and transport strategies results in the unsustainability of urban areas and, therefore, in a significant loss of competitiveness.

Management of Urban Mobility to Control Climate Change in Cities

The need of decarbonization of urban mobility is one of the main priorities for all countries to achieve greenhouse gas (GHG) emissions reduction targets. In general, the transport modes which have experienced the most growth in recent years tend to be the most polluting. Most efforts have been focused on the vehicle efficiency improvements and vehicle fleet renewal; nevertheless more emphasis should be placed on strategies related to the management of urban mobility and modal share. Research of individual travel which analyzes CO2 emissions and car and public transport share in daily mobility will enable better assessments of the potential of urban mobility measures introduced to limit GHG emissions produced by transport in cities. This paper explores the sustainability impacts of daily mobility in Spain using data from two National Travel Surveys (NTSs) (2000 and 2006) and includes a method by which to estimate the CO2 emissions associated with each journey and each surveyed individual. The results demonstrate that in the 2000 to 2006 period, there has been an increase in daily mobility which has led to a 17% increase in CO2 emissions. When separated by transport mode, cars prove to be the main contributor to that increase, followed by public transport. More focus should be directed toward modal shift strategies which not only take the number of journeys into account but also consider distance. The contributions of this paper have potential applications in the assessment of current and future urban transport policies.

Management of urban mobility to control climate change in cities in Spain

The need to decarbonize urban mobility is one of the main motivations for all countries to achieve reduction targets for greenhouse gas (GHG) emissions. In general, the transport modes that have experienced the most growth in recent years tend to be the most polluting. Most efforts have focused on improvements in vehicle efficiency and on the renewal of vehicle fleets; more emphasis should be placed on strategies related to the management of urban mobility and modal share. Research of individual travel that analyzes carbon dioxide (CO2) emissions and car and public transport share in daily mobility will enable better assessments of the potential of urban mobility measures introduced to limit GHG emissions produced by transport in cities. The climate change impacts of daily mobility in Spain are explored with data from two national travel surveys in 2000 and 2006, and a method for estimating the CO2 emissions associated with each journey and each surveyed individual is provided. The results demonstrate that from 2000 to 2006, daily mobility has increased and has led to a 17% increase in CO2 emissions. When these results are separated by transport mode, cars prove to be the main contributor to that increase, followed by public transport. More focus should be directed toward modal shift strategies, which take into account not only the number of journeys but also the distance traveled. These contributions have potential applications in the assessment of current and future urban transport policies related to low-carbon urban transportation.

Preferential exclusion of sucrose from recombinant interleukin-1 receptor antagonist: Role in restricted conformational mobility and compaction of native state

Understanding the mechanism for sucrose-induced protein stabilization is important in many diverse fields, ranging from biochemistry and environmental physiology to pharmaceutical science. Timasheff and Lee [Lee, J. C. & Timasheff, S. N. (1981) J. Biol. Chem. 256, 7193–7201] have established that thermodynamic stabilization of proteins by sucrose is due to preferential exclusion of the sugar from the protein’s surface, which increases protein chemical potential. The current study measures the preferential exclusion of 1 M sucrose from a protein drug, recombinant interleukin 1 receptor antagonist (rhIL-1ra). It is proposed that the degree of preferential exclusion and increase in chemical potential are directly proportional to the protein surface area and that, hence, the system will favor the protein state with the smallest surface area. This mechanism explains the observed sucrose-induced restriction of rhIL-1ra conformational fluctuations, which were studied by hydrogen–deuterium exchange and cysteine reactivity measurements. Furthermore, infrared spectroscopy of rhlL-1ra suggested that a more ordered native conformation is induced by sucrose. Electron paramagnetic resonance spectroscopy demonstrated that in the presence of sucrose, spin-labeled cysteine 116 becomes more buried in the protein’s interior and that the hydrodynamic diameter of the protein is reduced. The preferential exclusion of sucrose from the protein and the resulting shift in the equilibrium between protein states toward the most compact conformation account for sucrose-induced effects on rhIL-1ra.

Maintenance of Epstein–Barr virus (EBV) oriP-based episomes requires EBV-encoded nuclear antigen-1 chromosome-binding domains, which can be replaced by high-mobility group-I or histone H1

EBV-encoded nuclear antigen-1 (EBNA-1) binding to a cis-acting viral DNA element, oriP, enables plasmids to persist in dividing human cells as multicopy episomes that attach to chromosomes during mitosis. In investigating the significance of EBNA-1 binding to mitotic chromosomes, we identified the basic domains of EBNA-1 within amino acids 1–89 and 323–386 as critical for chromosome binding. In contrast, the EBNA-1 C terminus (amino acids 379–641), which includes the nuclear localization signal and DNA-binding domain, does not associate with mitotic chromosomes or retain oriP plasmid DNA in dividing cell nuclei, but does enable the accumulation of replicated oriP-containing plasmid DNA in transient replication assays. The importance of chromosome association in episome maintenance was evaluated by replacing EBNA-1 amino acids 1–378 with cell proteins that have similar chromosome binding characteristics. High-mobility group-I amino acids 1–90 or histone H1–2 could substitute for EBNA-1 amino acids 1–378 in mediating more efficient accumulation of replicated oriP plasmid, association with mitotic chromosomes, nuclear retention, and long-term episome persistence. These data strongly support the hypothesis that mitotic chromosome association is a critical factor for episome maintenance. The replacement of 60% of EBNA-1 with cell protein is a significant step toward eliminating the need for noncellular protein sequences in the maintenance of episomal DNA in human cells.

Fos and Jun bend the AP-1 site: effects of probe geometry on the detection of protein-induced DNA bending.

The effect of Fos and Jun binding on the structure of the AP-1 recognition site is controversial. Results from phasing analysis and phase-sensitive detection studies of DNA bending by Fos and Jun have led to opposite conclusions. The differences between these assays, the length of the spacer between two bends and the length of the sequences flanking the bends, are investigated here using intrinsic DNA bend standards. Both an increase in the spacer length as well as a decrease in the length of flanking sequences resulted in a reduction in the phase-dependent variation in electrophoretic mobilities. Probes with a wide separation between the bends and short flanking sequences, such as those used in the phase-sensitive detection studies, displayed no phase-dependent mobility variation. This shape-dependent variation in electrophoretic mobilities was reproduced by complexes formed by truncated Fos and Jun. Results from ligase-catalyzed cyclization experiments have been interpreted to indicate the absence of DNA bending in the Fos-Jun-AP-1 complex. However, truncated Fos and Jun can alter the relative rates of inter- and intramolecular ligation through mechanisms unrelated to DNA bending, confounding the interpretation of cyclization data. The analogous phase- and shape-dependence of the electrophoretic mobilities of the Fos-Jun-AP-1 complex and an intrinsic DNA bend confirm that Fos and Jun bend DNA, which may contribute to their functions in transcription regulation.

Modifications post-traductionnelles des canaux calciques cardiaques de type L : identification des résidus asparagine qui participent à la glycosylation de la sous-unité auxiliaire CaVα2δ1

Les canaux calciques de type L CaV1.2 sont principalement responsables de l’entrée des ions calcium pendant la phase plateau du potentiel d’action des cardiomyocytes ventriculaires. Cet influx calcique est requis pour initier la contraction du muscle cardiaque. Le canal CaV1.2 est un complexe oligomérique qui est composé de la sous-unité principale CaVα1 et des sous-unités auxiliaires CaVβ et CaVα2δ1. CaVβ joue un rôle déterminant dans l’adressage membranaire de la sous-unité CaVα1. CaVα2δ1 stabilise l’état ouvert du canal mais le mécanisme moléculaire responsable de cette modulation n’a pas été encore identifié. Nous avons récemment montré que cette modulation requiert une expression membranaire significative de CaVα2δ1 (Bourdin et al. 2015). CaVα2δ1 est une glycoprotéine qui possède 16 sites potentiels de glycosylation de type N. Nous avons donc évalué le rôle de la glycosylation de type-N dans l’adressage membranaire et la stabilité de CaVα2δ1. Nous avons d’abord confirmé que la protéine CaVα2δ1 recombinante, telle la protéine endogène, est significativement glycosylée puisque le traitement à la PNGase F se traduit par une diminution de 50 kDa de sa masse moléculaire, ce qui est compatible avec la présence de 16 sites Asn. Il s’est avéré par ailleurs que la mutation simultanée de 6/16 sites (6xNQ) est suffisante pour 1) réduire significativement la densité de surface de! CaVα2δ1 telle que mesurée par cytométrie en flux et par imagerie confocale 2) accélérer les cinétiques de dégradation telle qu’estimée après arrêt de la synthèse protéique et 3) diminuer la modulation fonctionnelle des courants générés par CaV1.2 telle qu’évaluée par la méthode du « patch-clamp ». Les effets les plus importants ont toutefois été obtenus avec les mutants N663Q, et les doubles mutants N348Q/N468Q, N348Q/N812Q, N468Q/N812Q. Ensemble, ces résultats montrent que Asn663 et à un moindre degré Asn348, Asn468 et Asn812 contribuent à la biogenèse et la stabilité de CaVα2δ1 et confirment que la glycosylation de type N de CaVα2δ1 est nécessaire à la fonction du canal calcique cardiaque de type L.

The role of transport and mobility in the health of older people

The world's population is ageing. Older people are healthier and more active than previous generations. Living in a hypermobile world, people want to stay connected to dispersed communities as they age. Staying connected to communities and social networks enables older people to contribute and connect with society and is associated with positive mental and physical health, facilitating independence and physical activity while reducing social isolation. Changes in physiology and cognition associated with later life mean longer journeys may have to be curtailed. A shift in focus is needed to fully explore older people, transport and health; a need to be multidisciplinary in approach and to embrace social sciences and arts and humanities. A need to embrace different types of mobilities is needed for a full understanding of ageing, transport and health, moving from literal or corporeal through virtual and potential to imaginative mobility, taking into account aspirations and emotions. Mobility in later life is more than a means of getting to destinations and includes more affective or emotive associations. Cycling and walking are facilitated not just by improving safety but through social and cultural norms. Car driving can be continued safely in later life if people make appropriate and informed decisions about when and how to stop driving; stringent testing of driver ability and skill has as yet had little effect on safety. Bus use facilitates physical activity and keeps people connected but there are concerns for the future viability of buses. The future of transport may be more community led and involve more sharing of transport modes.