bluuebunny/crossref_metadata_2025 huggingface dataset:
First indications of a sharp population decline in the globally threatened Spoon-billed Sandpiper Eurynorhynchus pygmeus
Authors: Tomkovich P. S. , Syroechkovski, Jr. E. E. , Lappo E. G. , Zöckler C.
Published: July 2002

Spoon-billed Sandpiper Eurynorhynchus pygmeus is classed as globally Vulnerable, based on the only available population estimate, made in 1977, of 2,000–2,800 pairs. Surveys for breeding Spoon-billed Sandpipers were carried out in summer 2000 on the Anadyr estuary coast, the Chukotka autonomous region, Russia. Although six new breeding sites were found, only 16–17 breeding males/pairs were recorded on the northern coast of the Anadyr estuary and five males/pairs on the southern coast and more southerly lagoons. These numbers were much lower than expected, and the species was not recorded in several apparently suitable areas. Four formerly known breeding sites held only one displaying male between them. At no site was there evidence of an increasing or stable local population. Together with other indicative data these suggest a sharp decline in the population of Spoon-billed Sandpiper. The previous population size estimate obviously requires updating, both because there were some incorrect assumptions in the calculations made for the first population estimate, and also due to a recent population decline. It is likely that the current population numbers under 1,000 breeding pairs. Given that the population of this species may be substantially lower than the only previous estimate, and the evidence for a possible rapid decline in its population described in this paper, it is recommended that its IUCN status is changed from Vulnerable to Endangered. No reasons for the apparent rapid rate of decline are evident within the breeding range. “Bottle-necks” should be looked for at migration sites or wintering grounds, but currently, monitoring of the population is only possible on the breeding grounds.
Normal forms for context-free node-rewriting hypergraph grammars
Authors: KLEMPIEN-HINRICHS RENATE
Published: July 2002

Confluent node-rewriting hypergraph grammars represent the most comprehensive known
method for defining sets of hypergraphs in a recursive way. For a large natural subclass of
these grammars, we show that the maximal rank of hyperedges indispensable for generating
some set of hypergraphs equals the maximal rank of the hyperedges occurring in the
hypergraphs of that set. Moreover, if such a grammar generates a set of graphs, one can
construct from that grammar a C-edNCE graph grammar generating the same set of graphs.
Pushout complements for partly total algebras
Authors: BURMEISTER PETER , LLABRÉS MERCÈ , ROSSELLÓ FRANCESC
Published: July 2002

Let Σ be an arbitrary signature and ϒ be a non-empty set of operation symbols within it. A
(partial) Σ-algebra is ϒ-total when all its operations in ϒ are total: these are the
partly total algebras in the title, and they include total algebras and attributed graphs. In this paper we
establish a necessary and sufficient condition on a pair of homomorphisms of ϒ-total
Σ-algebras for the existence of a pushout complement of them. This solves the application
problem for the double-pushout transformation of these kinds of structure.
FLORISTICS AND PHYTOSOCIOLOGY OF THE GALLERY FOREST OF THE BACABA STREAM, NOVA XAVANTINA, MATO GROSSO, BRAZIL
Authors: MARIMON B. S. , FELFILI J. M. , LIMA E. S.
Published: July 2002

The study was carried out on the gallery forest of the Bacaba stream situated in the Municipal Ecological Reserve ‘Mário Viana’ (14°43′S, 52°21′W) in Nova Xavantina, Eastern Mato Grosso, Brazil. Three sections of the gallery (upper, middle and lower) running downstream and differing in slope were surveyed by stratified sampling. Fortyseven nested 10m × 10m plots were analysed in each section, giving a total sampling area of 1.41ha overall. All trees or lianas ≥ 15cm girth at breast height were recorded and a total of 129 species belonging to 105 genera and 47 families were found. Diversity was high, with the Shannon index ranging from 3.84 nats/individual in the lower section to 4.08 in the middle section. The most important families (IVI) were Caesalpiniaceae (upper and middle sections) and Arecaceae (lower section), and the most important species were Diospyros obovata (upper section), Hymenaea courbaril var. stilbocarpa (middle section) and Mauritia flexuosa (lower section). Morisita and Sørensen indices of similarity were calculated. The floristic composition was complex and included species in common with a number of Brazilian forest types and with cerrado (savanna), as well as many widespread species, but stronger links with Amazonian forests could be detected. This is to be expected since the area lies in the ecotonal zone of the cerrado and Amazonian forest biomes and the Bacaba stream itself is a tributary of the Mortes–Araguaia–Amazon river system.
Franco's Request to the Third Reich for Military Assistance
Authors: Viñas Angel , Seidel Carlos Collado
Published: July 2002

This article traces the early contacts between the Spanish anti-Republican conspirators and Germany prior to the outbreak of the Civil War in July 1936. It offers new insights into the role played by General Sanjurjo in the run-up to the coup d'état and highlights the importance of chance and personality in the process which led to the Nazi intervention in Spain. The activities of Admiral Canaris' Abwehr as well as of the Gestapo, the Wehrmacht and the Nazi party prior to the coup are also reassessed. The article uses new Spanish archival evidence to identify how Franco's emissaries met with Hitler, while General Mola's emissaries followed in the wake of the contacts established by Sanjurjo. It challenges the role attributed to the German businessman Johannes Bernhardt enshrined in existing literature. Its conclusions also challenge existing military and economic interpretations of Hitler's decision to assist Franco by asserting the importance of large strategic motives behind the Führer's move.
The Road to Concorde: Franco-British Relations and the Supersonic Project
Authors: Johnman Lewis , Lynch Frances M. B.
Published: July 2002

In November 1962 the British and French governments signed an irreversible agreement to build together the Western world's first civil supersonic aeroplane: Concorde. This article explores the background to the agreement, looking in particular at why Britain and France co-operated with each other rather than with the United States or West Germany, the other possible partners. The central argument is that the agreement was driven not by technological convergence in the aircraft industry but by a weakening of Britain's position in 1961 caused by American unwillingness to partner Britain in the supersonic adventure and Britain's decision to apply for membership of the Common Market. The French government was then able to exploit that weakness in order to acquire technological expertise particularly in the field of aircraft engine construction.
The Road to Fascism: an Italian Sonderweg?
Authors: Corner Paul
Published: July 2002

The article argues that many of the factors which eventually produced Italian fascism should be identified not in the divisions of the war years nor in the conflicts of the immediate postwar period but in the period 1900–15 and in the failure of Giovanni Giolitti's reformist strategy. The increasing popular disaffection with parliamentary politics before the war reflected the inability of Giolitti to widen the political base of liberalism through significant social reform. It was this failure which made the experience of the First World War especially disastrous in Italy. In particular, it is argued that liberal governments totally failed to understand the kind of social conflict which was developing in the large estates of the Po valley – the area which would provide the specific context for the explosion of Fascism in late 1920. The essay links Fascism, therefore, less to an often cited ‘working class revolutionary threat’ in 1919–20 than to unresolved long-term structural problems in certain areas of rural Italy. Alexander De Grand offers a critical commentary on Paul Corner's conclusions and the author gives his response.
The Making of the GDR: New Research on its Formative Years and Problems
Authors: Lammers Karl Christian
Published: July 2002

Andreas Malycha, Die SED. Geschichte ihrer Stalinisierung 1946–1953 (Paderborn: Ferdinand Schöningh, 2000), 541 pp., DM 98.00, ISBN 3-506-75331-2. Gareth Pritchard, The making of the GDR 1945–53. From antifascism to Stalinism (Manchester: Manchester University Press, 2000), 244 pp., £45.00, ISBN 0-7190-5654-3. Mark Allinson, Politics and popular opinion in East Germany 1945–68 (Manchester: Manchester University Press, 2000), 178 pp., £45.00, ISBN 0-7190-5554-7. Jonathan Grix, The Role of the Masses in the Collapse of the GDR (Basingstoke/New York: Macmillan/Palgrave, 2000), 213 pp., £45.00, ISBN 0-333-80098-2. Raymond G. Stokes, Constructing Socialism. Technology and Change in East Germany, 1945–1990 (Baltimore: The Johns Hopkins University Press, 2000) 260 pp., $51.00, ISBN 0-8018-6391-0. Mary Fulbrook, German National Identity after the Holocaust (Cambridge: Polity Press, 1999), 248pp., £14.99, ISBN 0-7456-1045-5. Detlef Nakath and Gerd-Rüdiger Stephan, Die Häber-Protokolle. Schlaglichter der SED–Westpolitik 1973–1985 (Berlin: Karl Dietz Verlag, 1999), 480 pp., DM 48.00, ISBN 3-320-01968-6. Benno-Eide Siebs, Die Aussenpolitik der DDR 1976–1989. Strategien und Grenzen (Paderborn: Ferdinand Schöningh, 1999), 461 pp., DM 128.00, ISBN 3-506-77510-3.
IS MENSTRUATION NORMAL? SUPPRESSION OF THE MENSTRUAL CYCLE IN CLINICAL PRACTICE
Authors: Coutinho EM
Published: July 2002

According to Webster's Universal College Dictionary (Random House, 1997), normal means “conforming to the standard or the common type; usual regular, natural; free of any mental disorder; sane; free from disease or malformation”. On the basis of these various definitions, the answer to the question posed in the title of this review should be an unequivocal “no”. Incessant menstruation for years on end as it occurs today is certainly not natural, nor is it free of any mental disorder or free from disease. In fact, it conforms to no standard and it may cause serious dysphoric disorders and several diseases, of which anaemia and endometriosis are outstanding examples.
The oviduct and development of the preimplantation embryo
Authors: Yeung WSB , Lee CKF , Xu JS
Published: July 2002

Fertilization and early embryo development take place in the oviduct in vivo. Relative to studies in other reproductive organs, the importance of the oviduct has been ignored for many years because pregnancies can be obtained in assisted reproduction treatment using in-vitro fertilization (IVF) and embryo transfer to the uterus without involving the Fallopian tube. After the reports on the beneficial effect of oviductal cells on embryo development in sheep and subsequently in human, and a practical need to improve the success rates in clinical assisted reproduction, there was a period when more research was performed on the Fallopian tube. Many of these studies used in vitro coculture systems to emulate the in vivo environment in vitro, and to search for oviduct-derived embryotrophic factors. With the recent development of sequential culture to improve embryo development in vitro, the use of coculture in assisted reproduction and its related research declined because routine use of coculture is laborious and experience-dependent.
Topological techniques for efficient rigorous computation in dynamics
Authors: Mischaikow Konstantin
Published: July 2002

We describe topological methods for the efficient, rigorous computation of
dynamical systems. In particular, we indicate how Conley's Fundamental
Decomposition Theorem is naturally related to combinatorial approximations
of dynamical systems. Furthermore, we show that computations of Morse
decompositions and isolating blocks can be performed efficiently. We conclude
with examples indicating how these ideas can be applied to finite- and infinite-dimensional
discrete and continuous dynamical systems.
Permutation Pseudographs
and Contiguity
Authors: GREENHILL CATHERINE , JANSON SVANTE , KIM JEONG HAN , WORMALD NICHOLAS C.
Published: July 2002

The space of permutation pseudographs is a probabilistic model of 2-regular pseudographs
on n vertices, where a pseudograph is produced by choosing a permutation σ of
{1,2,…, n}
uniformly at random and taking the n edges
{i,σ(i)}. We prove several contiguity results
involving permutation pseudographs (contiguity is a kind of asymptotic equivalence of
sequences of probability spaces). Namely, we show that a random 4-regular pseudograph
is contiguous with the sum of two permutation pseudographs, the sum of a permutation
pseudograph and a random Hamilton cycle, and the sum of a permutation pseudograph
and a random 2-regular pseudograph. (The sum of two random pseudograph spaces is
defined by choosing a pseudograph from each space independently and taking the union
of the edges of the two pseudographs.) All these results are proved simultaneously by
working in a general setting, where each cycle of the permutation is given a nonnegative
constant multiplicative weight. A further contiguity result is proved involving the union of
a weighted permutation pseudograph and a random regular graph of arbitrary degree. All
corresponding results for simple graphs are obtained as corollaries.
Packing Trees into
the Complete Graph
Authors: DOBSON EDWARD
Published: July 2002

Let c [les ] 0.076122 and T1, T2,…, Tn be a sequence of trees such that
[mid ]V(Ti)[mid ] [les ] i−c(i−1).
We prove that, if for each 1 [les ] i [les ] n there exists a vertex xi ∈ V(Ti) such that Ti−xi has at least (1−2c)(i−1) isolated vertices, then T1,…, Tn can be packed into Kn. We also prove that if T is a tree of order n+1−c′n, c′ [les ]
1/25
(37−8
√21
) ≈ 0.0135748, such that there exists a vertex x ∈ V(T) and T−x has at least n(1−2c′) isolated vertices, then 2n+1 copies of T may be packed into K2n+1.
Births of calves derived from embryos produced by intracytoplasmic sperm injection without exogenous oocyte activation
Authors: Wei Hong , Fukui Yukata
Published: July 2002

Tail-cut bovine spermatozoa were microinjected into ooplasmic lipid polarised, in vitro matured bovine oocytes using a piezomicropipette-driving system. No exogenous oocyte activation treatment was used. Of the sperm-injected oocytes, 86.3% were activated, 71.8% cleaved and 22.7% developed to the blastocyst stage. The average cell count of the blastocysts was 122.5 ± 15 and a majority (81.8%) of the blastocysts were cytologically normal (diploid). When transferred to recipient cows, 5 of 8 blastocysts developed to fetuses and 4 of 7 recipients became pregnant. Normal offspring were born.
Ultrastructural characteristics of the follicle cell-oocyte interface in the oogenesis of Ceratophrys cranwelli
Authors: Villecco Evelina I. , Genta Susana B. , Sánchez Riera Alicia N. , Sánchez Sara S.
Published: July 2002

In this work we carried out an ultrastructural analysis of the cell interface between oocyte and follicle cells during the oogenesis of the amphibian Ceratophrys cranwelli, which revealed a complex cell-cell interaction. In the early previtellogenic follicles, the plasma membrane of the follicle cells lies in close contact with the plasma membrane of the oocyte, with no interface between them. In the mid-previtellogenic follicles the follicle cells became more active and their cytoplasm has vesicles containing granular material. Their apical surface projects cytoplasmic processes (macrovilli) that contact the oocyte, forming gap junctions. The oocyte surface begins to develop microvilli. At the interface both processes delimit lacunae containing granular material. The oocyte surface has endocytic vesicles that incorporate this material, forming cortical vesicles that are peripherally arranged. In the late previtellogenic follicle the interface contains fibrillar material from which the vitelline envelope will originate. During the vitellogenic period, there is an increase in the number and length of the micro- and macrovilli, which become regularly arranged inside fibrillar tunnels. At this time the oocyte surface exhibits deep crypts where the macrovilli enter, thus increasing the follicle cell-oocyte junctions. In addition, the oocyte displays coated pits and vesicles evidencing an intense endocytic activity. At the interface of the fully grown oocyte the fibrillar network of the vitelline envelope can be seen. The compact zone contains a fibrillar electron-dense material that fills the spaces previously occupied by the now-retracted microvilli. The macrovilli are still in contact with the surface of the oocyte, forming gap junctions.
Publications on financial history 1999
Authors: NOIRET SERGE
Published: July 2002

This bibliography covers publications that appeared during 1999. It follows previous criteria, being divided into two broad areas: general literature in financial history in section 1, and specialised material in section 2. Section 2 is subdivided chronologically and, further, by geographical area (the complete classification scheme was published in Volume 1, Part 2, October 1994, pp. 157–60.) Where there are no entries for a particular section, the heading has been omitted. Abbreviations have been kept to a minimum, but standard abbreviations such as J. for Journal, Q. for Quarterly, or Rev. for Review/Revue, have been used throughout. Short titles are used for references to edited volumes within the section in which they are listed; elsewhere they are cited in full. Articles published in books ‘edited by’ are mentioned only if the bibliographer accessed the index of the book before the deadline of the publication. Doctoral theses and Working Papers are not included.
The Big Bang: status and prospects
Authors: LIDDLE ANDREW R.
Published: July 2002

The 20th century saw the establishment of the first quantitative theory seeking to describe the behaviour of the Universe as a whole – the Big Bang. This sets up a framework within which there has been great success in interpreting a wide range of observations, including the abundances of light chemical elements, the existence and spectrum of the cosmic microwave radiation, and the formation and evolution of galaxies. At the end of the 20th century, the surprising conclusion of the Big Bang theory is that 95% of the Universe is made of two different unknown types of material whose nature remains unclear: dark matter and dark energy. Needless to say, this is a major challenge for science. At the beginning of the 21st century, cosmology appears poised to enter a high-precision era, where the key quantities of cosmology will be determined to two or more significant figures. If cosmologists are on the right track, this will confirm the existence of dark matter and dark energy; if not, it will force us to revise our current picture of the Universe. Either way, the prospect is for exciting years ahead in cosmology.
The oldest stars and the age of the Universe
Authors: CLEMENTINI GISELLA , GRATTON RAFFAELE
Published: July 2002

The Big Bang created primordial material from which the first stars formed. These stars exploded as supernovae and polluted the material from which subsequent generations of stars were made. Astronomers have had difficulty in finding stars made of the pure Big Bang material, but they have found stars with very little polluting material. The age of these cosmological relics of the first eras sets a lower limit for the age of the Universe we live in. European astronomers and their colleagues worldwide have joined in the effort to discover and date these, the oldest stars, and cast a glance into the obscure phases between the very first seconds of the existence of the Universe and the epoch at which galaxies and clusters of stars matured. Many independent techniques have been devised to date the oldest stars and stellar systems in the Universe. Some of them are briefly reviewed. The age of the oldest stars is now converging on a value in the range from 12 to 15 thousand million years. However, a large uncertainty still exists and a value as a large as 17 to18 thousand million years cannot be totally ruled out. Such a large value would be difficult to reconcile with the age of the Universe based on cosmological data. Significant improvements in the uncertainties of this situation are expected from the 8–1 m telescopes and space missions of the next decade.
Space weather
Authors: GLOVER ALEXI , DALY EAMONN , HILGERS ALAIN , BERGHMANS DAVID
Published: July 2002

Space weather is caused by conditions on the Sun and in the solar wind, the magnetosphere, ionosphere and thermosphere that can influence the performance and reliability of space-borne and ground-based technological systems and can affect human life or health. It affects man-made systems such as satellite electronics, terrestrial power grids and radio communications. This paper provides an overview of how space weather arises in the solar–terrestrial system and how physical processes are able to cause space weather effects. We also discuss European perspectives and activities geared towards the possible initiation of a European Space Weather programme.
Regional variation in the English verb qualifier system
Authors: Sampson Geoffrey
Published: July 2002

Nonstandard dialects often use the same form for the past tense and past participle of irregular verbs for which the standard language has distinct forms. One possible reason would be that some speakers have a nonstandard system of verb qualifiers (tense, mood, and aspect markers) in which the past tense/past participle distinction is functionally redundant. Data on spontaneous speech in Britain in the 1990s partly supports this by showing marked regional variation in the use of the Perfect construction. However, some nonstandard past tenses cannot be explained in terms of a nonstandard qualifier system.
Cross‐taxon congruence in complementarity and conservation of temperate biodiversity
Authors: Lund Mette Palitzsch , Rahbek Carsten
Published: July 2002

Identification of reliable surrogate indicator taxa and effective shortcuts for the preservation of overall biodiversity is a major challenge. Encouragingly, complementarity‐derived priority sets of focal taxa were found highly effective in representing non‐target taxa in a study from Ugandan forests. It has been proposed cross‐taxon congruence in complementarity is less distinct in temperate regions than in the tropics, because temperate regions have fewer species, and hence focal taxa may be less effective as they are less diverse. To test this, we used all available atlas data (10 × 10 km scale) in Denmark (butterflies, birds, amphibians, reptiles, large moths, bats and click beetles, n= 434 species), and looked at whether conservation priority areas based on one taxonomic group represent species richness of other groups in a highly fragmented landscape. We apply a new approach (based on G‐statistics) that enables statistical evaluation of cross‐taxon congruence in complementarity‐derived priority sets. We found indications that the same taxa represented other groups effectively and exhibited cross‐taxon congruence in complementarity‐derived priority sets. Birds performed significantly, but relatively poorly, butterflies somewhat better and bats relatively well in representing species richness of other groups. Large moths performed best and may be an overlooked predictor of diversity in other animal taxa.
The Agent–Structure Debate and America's Vietnam Options: A Reply to Professor Gavan Duffy
Authors: Khong Yuen Foong
Published: July 2002

This article responds to Gavan Duffy's critique of Analogies at War in his recent essay on the agent-structure debate in the JJPS (2001, 2: 161–175). I argue that Duffy's use of Analogies at War to pursue his thesis about “giving structure its due” is flawed because he (1) fails to assess the book in terms of the outcomes it seeks to explain; (2) conflates “structure” with process, perceptual, and personality variables; (3) misinterprets my assumptions while neglecting the findings of recent works that corroborate the findings of Analogies at War; and (4) fails to demonstrate one of his key suggestions, i.e. the importance of showing how agents and structures are mutually constitutive. The article concludes by discussing some pointers raised by the exchange for furthering the agent-structure debate.
Business versus Families: Whose Side is New Labour on?
Authors: Dean Hartley
Published: July 2002

In its proposals for achieving a better ‘work–life balance’ for Britain's working families, the New Labour government is also seeking to balance the interests of business against the needs of families. This article argues that the economic policy ‘trilemma’ resulting from economic globalisation is mirrored in a parallel family policy trilemma, with particular consequences for the poorest families. Drawing upon this argument and, partly, upon illustrative evidence from a small-scale qualitative study of low-income working families, it is suggested that promoting family friendly employment alongside a policy of welfare-to-work cannot reasonably be achieved without significant additional regulation of low-paying employers.
Gelatinase expression at positive patch test reactions
Authors: Giannelli Gianluigi , Foti Caterina , Marinosci Felice , Bonamonte Domenico , Antonaci Salvatore , Angelini Giovanni
Published: July 2002

Matrix metalloproteases (MMPs) are proteolytic enzymes involved in tissue remodelling and extracellular matrix (ECM) turnover. They are secreted in a latent form and activated at the cellular surface by a membrane type‐1 MMP (MT1‐MMP) and a tissue inhibitor of MMP‐2 (TIMP‐2) that is also responsible for striking a balance between the proteolytic enzymes and TIMP‐2. In allergic contact dermatitis (ACD) patients, MMP‐2 and MMP‐9, two members of the MMPs family, were increased during the challenge phase, in involved but not uninvolved skin. In contrast, TIMP‐2 was more evident in uninvolved than involved skin, while no differences were observed with regard to MT1‐MMP staining. Comparing the serum of ACD patients with that of healthy subjects, these differences were not observed. These data suggest that MMP‐2 and MMP‐9 could play a role in the mechanisms inducing alterations of the epidermal architecture, and in the pathogenesis of the lesions.
Prevention of experimental carotid and coronary artery thrombosis by the glycoprotein IIb/IIIa receptor antagonist CRL42796
Authors: Hennan James K , Hong Ting‐Ting , Willens David E , Driscoll Edward M , Giboulot Thierry A , Lucchesi Benedict R
Published: July 2002

The antithrombotic effect of the glycoprotein IIb/IIIa receptor antagonist, CRL42796, was examined in canine models of carotid and coronary artery thrombosis.

In the carotid artery thrombosis model, occlusion occurred in all control vessels (time to thrombosis 47.6±8.9 min). After treatment with low dose CRL42796 (15 μg kg−1 loading dose +0.31 μg kg−1 min−1 i.v.), two of five vessels occluded. Time to thrombosis increased significantly to 155.2±23.1 min. When the drug infusion was increased (0.69 μg kg−1 min−1), each of five vessels remained patent.

Ex vivo platelet aggregation in response to arachidonic acid (AA) and ADP was examined in platelet rich plasma (PRP) prepared from citrate or heparin anticoagulated blood. CRL42796 reduced platelet reactivity at low and high doses in PRP from citrate anticoagulated blood. However, in PRP from heparin anticoagulated blood, only the higher infusion dose produced a significant reduction in ex vivo platelet responses.

A combination of oral aspirin (4.6 mg kg−1 −41, −17 h) and the low infusion dose of CRL42796 did not produce an additional benefit beyond that provided by CRL42796 alone.

Coronary artery thrombosis was inhibited in four of five vessels treated with the lower infusion dose of CRL42796 and in five of five vessels treated with the higher infusion. Time to thrombosis increased with both doses (Control, 90.8±10.4 min; low dose, 165.8±14.2 min; high dose, >180.0±0 min).

The results indicate that CRL42796 is an effective in vivo antithrombotic agent against experimentally‐induced carotid and coronary artery thrombosis.

British Journal of Pharmacology (2002) 136, 927–937. doi:10.1038/sj.bjp.0704744
K+‐induced hyperpolarization in rat mesenteric artery: identification, localization and role of Na+/K+‐ATPases
Authors: Weston A H , Richards G R , Burnham M P , Félétou M , Vanhoutte P M , Edwards G
Published: July 2002

Mechanisms underlying K+‐induced hyperpolarizations in the presence and absence of phenylephrine were investigated in endothelium‐denuded rat mesenteric arteries (for all mean values,n=4).

Myocyte resting membrane potential (m.p.) was −58.8±0.8 mV. Application of 5 mMKCl produced similar hyperpolarizations in the absence (17.6±0.7 mV) or presence (15.8±1.0 mV) of 500 nMouabain. In the presence of ouabain +30 μMbarium, hyperpolarization to 5 mMKCl was essentially abolished.

In the presence of 10 μMphenylephrine (m.p. −33.7±3 mV), repolarization to 5 mMKCl did not occur in the presence or absence of 4‐aminopyridine but was restored (−26.9±1.8 mV) on addition of iberiotoxin (100 nM). Under these conditions the K+‐induced repolarization was insensitive to barium (30 μM) but abolished by 500 nMouabain alone.

In the presence of phenylephrine + iberiotoxin the hyperpolarization to 5 mMK+was inhibited in the additional presence of 300 nMlevcromakalim, an action which was reversed by 10 μMglibenclamide.

RT–PCR, Western blotting and immunohistochemical techniques collectively showed the presence of α1‐, α2‐ and α3‐subunits of Na+/K+‐ATPase in the myocytes.

In K+‐free solution, re‐introduction of K+(to 4.6 mM) hyperpolarized myocytes by 20.9±0.5 mV, an effect unchanged by 500 nMouabain but abolished by 500 μMouabain.

We conclude that under basal conditions, Na+/K+‐ATPases containing α2‐ and/or α3‐subunits are partially responsible for the observed K+‐induced effects. The opening of myocyte K+channels (by levcromakalim or phenylephrine) creates a ‘K+cloud’ around the cells which fully activates Na+/K+‐ATPase and thereby abolishes further responses to [K+]oelevation.

British Journal of Pharmacology(2002)136, 918–926. doi:10.1038/sj.bjp.0704787
Pharmacological evidence for putative CCK1 receptor heterogeneity in human colon smooth muscle
Authors: Morton M F , Harper E A , Tavares I A , Shankley N P
Published: July 2002

The pharmacology of the cholecystokinin CCK1 receptors endogenously expressed in human gallbladder and human ascending colon smooth muscle tissue was compared using radioligand binding assays.

Saturation analysis of the interaction between the radiolabelled, selective CCK1‐receptor antagonist, [3H]‐L‐364,718, and enriched gastrointestinal tissue membranes suggested the presence of multiple binding sites in human colon but not human gallbladder.

Competition studies, using a range of structurally diverse, CCK‐receptor selective ligands provided further evidence for CCK1 receptor heterogeneity in human colon tissue (nH values significantly less than unity for SR27897=0.77±0.07, 2‐NAP=0.73±0.03, YM220=0.70±0.09 and PD‐134,308=0.83±0.01). Moreover, the competition data for SR27897, 2‐NAP and YM220 were consistent with the interaction of these compounds at two binding sites. In contrast, in the human gallbladder assay, a single binding site model provided a good fit of the competition curve data obtained with all the CCK receptor selective compounds.

The data obtained are consistent with the presence of a single CCK1 receptor binding site in the gallbladder but not in the colon. A two‐site analysis of the colon data, indicated that one of the two sites was indistinguishable from that characterized in the gallbladder. The molecular basis of the apparent receptor heterogeneity in the colon remains to be established.

British Journal of Pharmacology (2002) 136, 873–882. doi:10.1038/sj.bjp.0704794
Ferritin binds to light chain of human H-kininogen and inhibits kallikrein-mediated bradykinin release
Authors: PARTHASARATHY Narayanan , TORTI Suzy V. , TORTI Frank M.
Published: July 2002

Ferritin is an iron-storage protein that exists in both intracellular and extracellular compartments. We have previously identified H-kininogen (high-molecular-weight kininogen) as a ferritin-binding protein [Torti and Torti (1998) J. Biol. Chem. 273, 13630–13635]. H-Kininogen is a precursor of the potent pro-inflammatory peptide bradykinin, which is released from H-kininogen following cleavage of H-kininogen by the serine protease kallikrein. In this report, we demonstrate that binding of ferritin to H-kininogen occurs via the modified light chain of H-kininogen, and that ferritin binds preferentially to activated H-kininogen. We further demonstrate that binding of ferritin to H-kininogen retards the proteolytic cleavage of H-kininogen by kallikrein and its subsequent release of bradykinin fromH-kininogen. Ferritin does not interfere with the ability of kallikrein to digest a synthetic substrate, suggesting that ferritin specifically impedes the ability of kallikrein to digest H-kininogen, perhaps by steric hindrance. Based on these results, we propose a model of sequential H-kininogen cleavage and ferritin binding. These results are consistent with the hypothesis that the binding of ferritin to H-kininogen may serve to modulate bradykinin release.
Differential metabolism of dihomo-γ-linolenic acid and arachidonic acid by cyclo-oxygenase-1 and cyclo-oxygenase-2: implications for cellular synthesis of prostaglandin E1 and prostaglandin E2
Authors: LEVIN Galit , DUFFIN Kevin L. , OBUKOWICZ Mark G. , HUMMERT Susan L. , FUJIWARA Hideji , NEEDLEMAN Philip , RAZ Amiram
Published: July 2002

Prostaglandin (PG) E1 has been shown to possess anti-inflammatory properties and to modulate vascular reactivity. These activities are sometimes distinct from those of PGE2, suggesting that endogenously produced PGE1 may have some beneficial therapeutic effects compared with PGE2. Increasing the endogenous formation of PGE1 requires optimization of two separate processes, namely, enrichment of cellular lipids with dihomo-γ-linolenic acid (20:3 n—6; DGLA) and effective cyclo-oxygenase-dependent oxygenation of substrate DGLA relative to arachidonic acid (AA; 20:4 n—6). DGLA and AA had similar affinities (Km values) and maximal reaction rates (Vmax) for cyclo-oxygenase-2 (COX-2), whereas AA was metabolized preferentially by cyclo-oxygenase-1 (COX-1). To overcome the kinetic preference of COX-1 for AA, CP-24879, a mixed Δ5/Δ6 desaturase inhibitor, was used to enhance preferential accumulation of DGLA over AA in cells cultured in the presence of precursor γ-linolenic acid (18:3 n—6). This protocol was tested in two cell lines and both yielded a DGLA/AA ratio of approx. 2.8 in the total cellular lipids. From the enzyme kinetic data, it was calculated that this ratio should offset the preference of COX-1 for AA over DGLA. PGE1 synthesis in the DGLA-enriched cells was increased concurrent with a decline in PGE2 formation. Nevertheless, PGE1 synthesis was still substantially lower than that of PGE2. It appears that employing a dietary or a combined dietary/pharmacological paradigm to augment the cellular ratio of DGLA/AA is not an effective route to enhance endogenous synthesis of PGE1 over PGE2, at least in cells/tissues where COX-1 predominates over COX-2.
The Saccharomyces cerevisiae 14-3-3 protein Bmh2 is required for regulation of the phosphorylation status of Fin1, a novel intermediate filament protein
Authors: MAYORDOMO Isabel , SANZ Pascual
Published: July 2002

In order to identify proteins that interact with Bmh2, a yeast member of the 14-3-3 protein family, we performed a two-hybrid screening using LexA-Bmh2 as bait. We identified Fin1, a novel intermediate filament protein, as the protein that showed the highest degree of interaction. We also identified components of the vesicular transport machinery such as Gic2 and Msb3, proteins involved in transcriptional regulation such as Mbf1, Gcr2 and Reg2, and a variety of other different proteins (Ppt1, Lre1, Rps0A and Ylr177w). We studied the interaction between Bmh2 and Fin1 in more detail and found that Bmh2 only interacted with phosphorylated forms of Fin1. In addition, we showed that Glc7, the catalytic subunit of the protein phosphatase 1 complex, was also able to interact with Fin1.
A method for detection of overoxidation of cysteines: peroxiredoxins are oxidized in vivo at the active-site cysteine during oxidative stress
Authors: WAGNER Elsa , LUCHE Sylvie , PENNA Lucia , CHEVALLET Mireille , van DORSSELAER Alain , LEIZE-WAGNER Emmanuelle , RABILLOUD Thierry
Published: July 2002

Peroxiredoxins are often encountered as double spots when analysed by two-dimensional electrophoresis. The quantitative balance between these two spots depends on the physiological conditions, and is altered in favour of the acidic variant by oxidative stress for all the peroxiredoxins we could analyse. Using HeLa cells as a model system, we have further analysed the two protein isoforms represented by the two spots for each peroxiredoxin. The use of selected enzyme digestion and MS demonstrated that the acidic variant of all the peroxiredoxins analysed is irreversibly oxidized at the active-site cysteine into cysteine sulphinic or sulphonic acid. Thus, this acidic variant represents an inactivation form of the peroxiredoxins, and provides a useful marker of oxidative damage to the cells.
Up-regulation of pyruvate dehydrogenase kinase isoform 4 (PDK4) protein expression in oxidative skeletal muscle does not require the obligatory participation of peroxisome-proliferator-activated receptor α (PPARα)
Authors: HOLNESS Mark J. , BULMER Karen , GIBBONS Geoffrey F. , SUGDEN Mary C.
Published: July 2002

In insulin deficiency, increased lipid delivery and oxidation suppress skeletal-muscle glucose oxidation by inhibiting pyruvate dehydrogenase complex (PDC) activity via enhanced protein expression of pyruvate dehydrogenase kinase (PDK) isoform 4, which phosphorylates (and inactivates) PDC. Signalling via peroxisome-proliferator-activated receptor α (PPARα) is an important component of the mechanism enhancing hepatic and renal PDK4 protein expression. Activation of PPARα in gastrocnemius, a predominantly fast glycolytic (FG) muscle, also increases PDK4 expression, an effect that, if extended to all muscles, would be predicted to drastically restrict whole-body glucose disposal. Paradoxically, chronic activation of PPARα by WY14,643 treatment improves glucose utilization by muscles of insulin-resistant high-fat-fed rats. In the resting state, oxidative skeletal muscles are quantitatively more important for glucose disposal than FG muscles. We evaluated the participation of PPARα in regulating PDK4 protein expression in slow oxidative (SO) skeletal muscle (soleus) and fast oxidative-glycolytic (FOG) skeletal muscle (anterior tibialis) containing a high proportion of oxidative fibres. In the fed state, acute (24h) activation of PPARα by WY14,643 in vivo failed to modify PDK4 protein expression in soleus, but modestly enhanced PDK4 protein expression in anterior tibialis. Starvation enhanced PDK4 protein expression in both muscles, with the greater response in anterior tibialis. WY14,643 treatment in vivo during starvation did not further enhance upregulation of PDK4 protein expression in either muscle type. Enhanced PDK4 protein expression after starvation was retained in SO and FOG skeletal muscles of PPARα-deficient mice. Our data indicate that PDK4 protein expression in oxidative skeletal muscle is regulated by a lipid-dependent mechanism that is not obligatorily dependent on signalling via PPARα.
Effect of smoking cessation counseling on recovery from alcoholism: findings from a randomized community intervention trial
Authors: Bobo Janet Kay , Mcilvain Helen E. , Lando Harry A. , Walker R. Dale , Leed‐Kelly Amber
Published: July 2002

Aims. To assess the effects of a smoking cessation program for recovering alcoholics on use of alcohol, tobacco and illicit drugs after discharge from residential treatment. Design and Setting. A randomized community intervention trial design was employed in which 12 residential drug treatment centers in Iowa, Kansas and Nebraska were matched and then randomly assigned to the intervention or control condition. Participants. Approximately 50 adult residents (inpatients) from each site were followed for 12 months after treatment discharge. Intervention. Participating residents in the six intervention centers received a 4‐part, individually tailored, smoking cessation program while those in the six control sites received usual care. Findings. Both moderate and heavy drinking rates were reduced in the intervention group. Intervention site participants were significantly more likely than controls to report alcohol abstinence at both the 6‐month (OR = 1.59, 95%CI: 1.09‐2.35) and 12‐month assessment (OR = 1.84, 95%CI:1.28‐2.92). Illicit drug use rates were comparable. Effect of the intervention on tobacco quit rates was not statistically significant. Conclusions. Counseling alcoholics in treatment to quit smoking does not jeopardize the alcohol recovery process. However, low‐intensity tobacco interventions are unlikely to yield high tobacco quit rates.
Psychiatric co‐morbidity, suicidal behaviour and suicidal ideation in alcoholics seeking treatment
Authors: Driessen Martin , Veltrup Clemens , Weber Jutta , John Ulrich , Wetterling Tilman , Dilling Horst
Published: July 2002

Aims. To estimate the impact of co‐morbid disorbers for suicidal ideas in alcohol‐dependent subjects seeking treatment. Design. Life‐time psychiatric co‐morbidity and previous suicidal behaviours were assessed retrospectively after detoxification ( t 1). In addition, suicidal behaviours were assessed 12 months after discharge ( t 2) . Setting. An inpatient detoxification treatment unit. Participants. Two hundred and fifty dependent inpatients were studied after detoxification. One hundred and forty‐nine of them participated in the follow‐up face‐to‐face interview. Measurements. Using two extended standardized interviews (CIDI and IPDE) psychiatric co‐morbidity (DSM‐III‐R, Axes I and II) was assessed at t 1; suicide attempts were reported at t 1 and t 2, and suicidal ideas were assessed at t 2. Findings. A history of suicide attempts was reported by 29.2% at t 1, and suicidal ideas by 14.1% and suicide attempts by 5.4% at the follow‐up ( t 2). One female patient committed suicide within 6 months of discharge from hospital. The following co‐morbidity patterns were associated with the greatest risk for suicidal ideas. Anxiety and depressive disorders, Axes I and II disorders, and a history of suicide attempt (for suicidal ideas at ( t 2). Conclusions. Our results underline the importance of psychiatric co‐morbidity for the suicidal risk in alcohol‐dependent patients, while alcoholism itself appears to be only a moderate risk factor.
Alcohol consumption in a national sample of the Russian population
Authors: Bobak Martin , Mckee Martin , Rose Richard , Marmot Michael
Published: July 2002

Aims. Alcohol has been suggested as an important determinant of mortality in Russia but survey data on individuals' alcohol consumption in Russia are sparse. We have analysed the levels and distribution of alcohol consumption in a national sample of the Russian population. Design. Cross‐sectional survey. Participants. A multi‐stage random sample of men and women of the Russian Federation (N = 1599, response rate 66%). Measurements. Data on frequency of drinking alcohol and the average amount consumed at one occasion were collected in an interview. Information was also collected on smoking, self‐rated health and a broad range of socio‐economic factors and political attitudes. Findings. Nine per cent of men and 35% of women reported that they never drink alcohol; 10% of men and 2% women drink several times a week; 44% of men and 6% of women reported that they drink an equivalent of 25 cl of vodka or more at one occasion and 31% of men and 3% of women would do so at least once a month (25 cl of vodka contains 78.5 g of absolute alcohol). There were differences in alcohol consumption between geographical areas. Material deprivation was not related to alcohol consumption. Among men, smokers, unmarried, unemployed and men reporting poor health consumed more alcohol; women with higher education, widows, non‐smoking and with worse health consumed less alcohol. Variables related to reaction to economic and political changes, rating of family economic situation general satisfaction or political preferences were not related to alcohol consumption. Conclusions. While the overall levels of alcohol consumption appeared low, possibly due to under‐reporting, the proportion of men who can be considered as "binge drinkers" was relatively high. The absence of sizable socio‐economic differences suggest that drinking may be spread relatively uniformly in Russia, especially among males. Alcohol consumption seems unrelated to individuals' perception of the recent societal changes.
Fibroblast growth factor receptors regulate the ability for hindlimb regeneration in Xenopus laevis
Authors: D'Jamoos Christopher A. , McMahon Gerald , Tsonis Panagiotis A.
Published: July 2002

During outgrowth of the developing limb, signals from the apical ectodermal ridge, such as fibroblast growth factors, are paramount for limb patterning. Similarly, fibroblast growth factor molecules and their receptors are synthesized in the wound epithelium of the regenerating limb blastema, implicating an analogous function to limb development. To address this issue further and to understand the role of fibroblast growth factor receptor signaling in limb regeneration, we have examined the expression patterns of x‐fibroblast growth factor receptors‐1, ‐2, ‐3, ‐4a, and ‐4b in Xenopus laevis. This amphibian model provides a system in which both regenerating (premetamorphic; tadpole or larva stage) and nonregenerating (postmetamorphic; froglet stage) hindlimbs can be studied. In premetamorphic hindlimbs (stage 53), all of the receptors were expressed in the wound epithelium and the underlying mesenchyme. In postmetamorphic limbs (stage 61), however, transcripts for x‐fibroblast growth factor receptors‐1 and ‐2 were absent from the wound epithelium. The expression results for x‐fibroblast growth factor receptors‐1 and ‐2 were corroborated at the protein level by employing specific antibodies. Thus, it appears that expression of both fibroblast growth factor receptors‐1 and ‐2 is associated with the ability for limb regeneration. The role of these receptors in regeneration was further investigated by using specific inhibitors to fibroblast growth factor receptors during premetamorphic hindlimb regeneration. These compounds inhibited the normal limb outgrowth and resulted, in the majority of the cases, in outgrowths of cones or spikes reminiscent of growth that is seen in amputated postmetamorphic limbs. Thus, fibroblast growth factor receptors‐1 and ‐2 expression and function should be regarded as paramount for the ability of limb regeneration in Xenopus.