A conserved serine-rich stretch in the glutamate transporter family forms a substrate-sensitive reentrant loop

Neuronal and glial glutamate transporters remove the excitatory neurotransmitter glutamate from the synaptic cleft. The proteins belong to a large family of secondary transporters, which includes bacterial glutamate transporters. The C-terminal half of the glutamate transporters is well conserved and thought to contain the translocation path and the binding sites for substrate and coupling ions. A serine-rich sequence motif in this part of the proteins is located in a putative intracellular loop. Cysteine-scanning mutagenesis was applied to this loop in the glutamate transporter GltT of Bacillus stearothermophilus. The loop was found to be largely intracellular, but three consecutive positions in the conserved serine-rich motif (S269, S270, and E271) are accessible from both sides of the membrane. Single-cysteine mutants in the serine-rich motif were still capable of glutamate transport, but modification with N-ethylmaleimide blocked the transport activity in six mutants (T267C, A268C, S269C, S270C, E271C, and T272C). Two milimolars l-glutamate effectively protected against the modification of the cysteines at position 269–271 from the periplasmic side of the membrane but was unable to protect cysteine modification from the cytoplasmic side of the membrane. The results indicate that the conserved serine-rich motif in the glutamate transporter forms a reentrant loop, a structure that is found in several ion channels but is unusual for transporter proteins. The reentrant loop is of crucial importance for the function of the glutamate transporter.

Femtosecond observation of benzyne intermediates in a molecular beam: Bergman rearrangement in the isolated molecule

In this communication, we report our femtosecond real-time observation of the dynamics for the three didehydrobenzene molecules (p-, m-, and o-benzyne) generated from 1,4-, 1,3-, and 1,2-dibromobenzene, respectively, in a molecular beam, by using femtosecond time-resolved mass spectrometry. The time required for the first and the second C-Br bond breakage is less than 100 fs; the benzyne molecules are produced within 100 fs and then decay with a lifetime of 400 ps or more. Density functional theory and high-level ab initio calculations are also reported herein to elucidate the energetics along the reaction path. We discuss the dynamics and possible reaction mechanisms for the disappearance of benzyne intermediates. Our effort focuses on the isolated molecule dynamics of the three isomers on the femtosecond time scale.

Shifts of Intracellular pH Distribution as a Part of the Signal Mechanism Leading to the Elicitation of Benzophenanthridine Alkaloids1 : Phytoalexin Biosynthesis in Cultured Cells of Eschscholtzia californica

Cultured cells of Eschscholtzia californica (Californian poppy) respond to a yeast elicitor preparation or Penicillium cyclopium spores with the production of benzophenanthridine alkaloids, which are potent phytoalexins. Confocal pH mapping with the probe carboxy-seminaphthorhodafluor-1-acetoxymethylester revealed characteristic shifts of the pH distribution in challenged cells: within a few minutes after elicitor contact a transient acidification of cytoplasmic and nuclear areas occurred in parallel with an increase of the vacuolar pH. The change of proton concentration in the vacuole and in the extravacuolar area showed a nearly constant relation, indicating an efflux of vacuolar protons into the cytosol. A 10-min treatment with 2 mm butyric or pivalic acid caused a transient acidification of the cytoplasm comparable to that observed after elicitor contact and also induced alkaloid biosynthesis. Experimental depletion of the vacuolar proton pool reversibly prevented both the elicitor-triggered pH shifts and the induction of alkaloid biosynthesis. pH shifts and induction of alkaloid biosynthesis showed a similar dependence on the elicitor concentration. Net efflux of K+, alkalinization of the outer medium, and browning of the cells were evoked only at higher elicitor concentrations. We suggest that transient acidification of the cytoplasm via efflux of vacuolar protons is both a necessary and sufficient step in the signal path toward biosynthesis of benzophenanthridine alkaloids in Californian poppy cells.

Circuit-specific alterations of N-methyl-D-aspartate receptor subunit 1 in the dentate gyrus of aged monkeys.

Age-associated memory impairment occurs frequently in primates. Based on the established importance of both the perforant path and N-methyl-D-aspartate (NMDA) receptors in memory formation, we investigated the glutamate receptor distribution and immunofluorescence intensity within the dentate gyrus of juvenile, adult, and aged macaque monkeys with the combined use of subunit-specific antibodies and quantitative confocal laser scanning microscopy. Here we demonstrate that aged monkeys, compared to adult monkeys, exhibit a 30.6% decrease in the ratio of NMDA receptor subunit 1 (NMDAR1) immunofluorescence intensity within the distal dendrites of the dentate gyrus granule cells, which receive the perforant path input from the entorhinal cortex, relative to the proximal dendrites, which receive an intrinsic excitatory input from the dentate hilus. The intradendritic alteration in NMDAR1 immunofluorescence occurs without a similar alteration of non-NMDA receptor subunits. Further analyses using synaptophysin as a reflection of total synaptic density and microtubule-associated protein 2 as a dendritic structural marker demonstrated no significant difference in staining intensity or area across the molecular layer in aged animals compared to the younger animals. These findings suggest that, in aged monkeys, a circuit-specific alteration in the intradendritic concentration of NMDAR1 occurs without concomitant gross structural changes in dendritic morphology or a significant change in the total synaptic density across the molecular layer. This alteration in the NMDA receptor-mediated input to the hippocampus from the entorhinal cortex may represent a molecular/cellular substrate for age-associated memory impairments.

Smart Sentinel: Monitoring and Prevention System in the Smart Cities

Today, faced with the constant rise of the Smart cities around the world, there is an exponential increase of the use and deployment of information technologies in the cities. The intensive use of Information Technology (IT) in these ecosystems facilitates and improves the quality of life of citizens, but in these digital communities coexist individuals whose health is affected developing or increasing diseases such as electromagnetic hypersensitivity. In this paper we present a monitoring, detection and prevention system to help this group, through which it is reported the rates of electromagnetic radiation in certain areas, based on the information that the own Smart City gives us. This work provides a perfect platform for the generation of predictive models for detection of future states of risk for humans.

The effects of quality and environmental management on competitive advantage: A mixed methods study in the hotel industry

This paper reports results derived from a mixed methods study where 13 hotel managers were initially interviewed, followed by a quantitative study of 355 additional managers. Data were analysed using partial least squares path modelling. The research question related to the relationship between quality and environmental management and the competitive advantage sought by hotels. The results indicate that quality management and environmental management permit the improvement of competitive advantage in terms of both costs and differentiation. Moreover, hotels implementing quality programmes find fewer obstacles in implementing environmental management.

A catalogue of books [donated by Jasper Mauduit] in the library of Harvard College [at]: Cambridge in New England, 1765

This leatherbound volume lists books donated to the Harvard College Library by Jasper Mauduit, who served as an agent in London on behalf of the Province of the Massachusetts Bay. Entries are arranged alphabetically and by format; i.e. the first page lists all folios whose author, title, or keyword begin with "A," the next page lists all quartos beginning with "A," and the following page lists all "octavo &ca" volumes beginning with "A." The volume continues in a similar manner for each letter of the alphabet. Following a devastating fire in 1764 which destroyed most of the books in the Harvard College Library, Mauduit donated books, as well as money for the purchase of books, to the College. He also acted as an agent of the Society for Propagating the Gospel in New England and Parts Adjacent, using the £300 they donated for the rebuilding of the College library to select and purchase a large number of books. It is not known if the books listed in this catalog are those donated by Mauduit himself, or if they are the donations he purchased on behalf of the Society. The creator of this volume is unknown; although all entries are made in the same hand, the identity of the writer has not been determined. The label attached to the front cover, which refers to the Lime Street address of Mauduit's business in London, suggests that the list might have been prepared by Mauduit himself.

Cittadinanza, lavoro e diritti sociali nella crisi europea = Citizenship, work and social rights in the European crisis. WP C.S.D.L.E. “Massimo D’Antona”.INT – 100/2013

This paper explores the limits and potentials of European citizenship as a transnational form of social integration, taking as comparison Marshall's classical analysis of the historical development of social rights in the context of the national Welfare State. It is submitted that this potential is currently frustrated by the prevailing negative-integration dimension in which the interplay between Union citizenship and national systems of Welfare State takes place. This negative dimension pervades the entire case law of the Court of Justice on Union citizenship, even becoming dominant – after the famous Viking and Laval judgements – in the ways in which the judges in Luxembourg have built, and limited, what in Marshall’s terms might be called the European collective dimension of “industrial citizenship”. The new architecture of the economic and monetary governance of the Union, based as it is on an unprecedented effort towards a creeping constitutionalisation of a neo-liberal politics of austerity and welfare retrenchment, is destined to strengthen the de-structuring pressures on the industrial-relation and social protection systems of the member States. The conclusions sum-up the main critical arguments and make some suggestions for an alternative path for re-politicising the social question in Europe.

Inequality in the Southern Mediterranean: A survey of selected countries. MEDPRO Technical Report No. 23/December 2012

This paper addresses the issues of current levels of inequality: their trends, determinants and future scenarios, demonstrating that welfare levels are measured by per capita consumption. Location, educational attainment and employment status have been identified as the key factors affecting levels of welfare and its distribution. A benefit incidence analysis was performed to investigate benefits of different deciles of per capita expenditure from education and health services. The inequality patterns in countries under investigation present significant variations; countries such as Turkey, Morocco and Tunisia show relatively high inequality while others, such as Egypt or Syria, show moderate to low inequality. Inequality in human development was addressed using the inequality-adjusted human development index (IHDI), introduced by Global HDR 2010. The average loss in the HDI due to inequality in all Arab countries under investigation is about 20%. Two reference scenarios (optimistic and pessimistic) were used to project future paths up to 2020 and 2030. The impact of positive growth is increasing inequality and a shrinking middle class. Results show that the rich benefit most from this growth path. The opposite trend is observed for the pessimistic scenario.

Skill formation in Britain and Germany: Recent developments in the context of traditional differences. CES Germany & Europe Working Papers, No.06.1, 2006

This paper proposes a comparison of skill formation in Germany and Britain over the last decades. Taking historical trends into account, the two cases can be regarded as representing different types of skill production regimes. Institu-tional features include a relatively low degree of standardization of training and a larger amount of on-the-job training in Britain. In Germany, post-compulsory training has been conducted predominantly within the dual system of vocational training, underlining the vocational specificity of a large part of the labor market. As a consequence, international differences in individual skill investments, transitions from school to work and other life-course patterns can be observed. At least in Britain, however, the situation seems to have changed considerably during the 1990s. The paper argues that the divergence in more recent developments can still be understood as an expression of historical path-dependency given the traditional connections between the post-compulsory training system and the broader societal context in which it is embedded. These concern, in particular, links with the system of general and academic education as the basis for – and also a possible competitor with – vocational training; links with the labor market as they are indicated by specific skill requirements and returns to qualifications; and, links with the order of social stratification in the form of the selective acquisition and the social consequences of these qualifications. The links manifest themselves as typical individual-level consequences and decisions. Founded on the basis of these distinctions, the aim of this paper is to investigate the preceding conditions for recent developments in the qualification systems of Britain and Germany, which have adapted to specific challenges during the last decades.

Geochemistry of Fe-Mn crusts at seamounts in the Northwest Pacific

Hydrogenetic ferromanganese crusts were dredged from four seamounts in the western Pacific, OSM7, OSM2, Lomilik, and Lemkein, aligned in a NW-SE direction parallel to Pacific Plate movement. The crusts consist of four well-defined layers with distinct textural and geochemical properties. The topmost layer 1 is relatively enriched in Mn, Co, Ni, and Mo compared to the underlying layer 2, which is relatively enriched in Al, Ti, K, and Rb and Cu, Zn, and excess Ba. Textural and geochemical properties of layer 2 suggest growth conditions under high biogenic and detrital flux. Such conditions are met in the equatorial Pacific (i.e., between the Intertropical Convergence Zone (ITCZ) and equatorial high-productivity zone). Layer 2 likely formed when each seamount was beneath the equatorial Pacific along its back track path. On the other hand, layer 1 probably started to grow after seamounts moved northwest from the ITCZ. This interpretation is consistent with the thickness of layer 1 across the four crusts, which increases to the northwest. Ages of the layer 1-layer 2 boundary in each crust, a potential proxy for northern margin of the ITCZ, also increase to the northwest at 17, 11, 8, and 5 Ma for OSM7, OSM2, Lomilik, and Lemkein, respectively. Assuming Pacific Plate motion of 0.3°/Myr, the seamounts were located at 12°N, 11°N, 9°N, and 8°N at the time of boundary formation. This result suggests that the north edge of the ITCZ has shifted south since the middle Miocene in the western Pacific, which agrees with information from the eastern Pacific.

The Theosophical path; illustrated monthly.

Plates printed on both sides.

Two upper bounds for the weighted path length of binary trees.

Thesis (M.S.)--University of Illinois at Urbana-Champaign.

Col. Thomas Cresap : a Maryland pioneer who cut the first path for the National Road /

Mode of access: Internet.

Tell-Trothes New Yeares gift ... And The passionate Morrice. 1593.--John Lane's Tom Tell-Troths message, and his pens complaint. 1600.--Thomas Powell's Tom of all trades. Or The plaine path-way to preferment ... 1631.--The glasse of Godly loue. (By John Rogers?) 1569.--

"The glasse of Godly loue" forms part of a tract entitled: The school of honest and vertuous lyfe ... by T[homas] P[ritchard] Also a ... discourse, of the worthynesse of honorable wedlocke ... by I[ohn] R[ogers]" It is uncertain who is the author. cf. Forewords.