bluuebunny/crossref_metadata_2025 huggingface dataset:
Die Fundmünzen von Harrān und ihr Verhältnis zur lokalen Geschichte
Authors: HEIDEMANN STEFAN
Published: October 2002

During the 1940s and 1950s D. Storm Rice and Seton Lloyd, together with the Turkish Antiquity Authority, undertook archaeological excavations in Harrān. With the exception of two preliminary reports and a few articles, the excavations remain largely unpublished.

The 264 coins constitute an independent source on the regional, political and economic history of Harrān. For the Umayyad and early Abbasid period, the coins constitute a source on the pattern of the city's regional integration. Two-thirds of the coins date from the Ayyubid period. The circulation is characterized by a competition of different coinages: first, those which were struck for the political entities to which Harrān belonged; and second, imported coins, i.e. of Byzantine and Rūm-Saljūq origin. Third, copper coins from Northern Syria, despite the fact that the Diyār Mudar and Northern Syria belong to different branches of the Ayyubid dynasty. Two dirhams of the Saljūq prince al-Malik Mas‘ūd, who resided in Mosul between 504/1111 and 511/1118, are historical documents of importance.
New sources for the study of Sufism in Mamluk Egypt
Authors: MCGREGOR RICHARD J. A.
Published: October 2002

This article is an introduction to the writings of two significant but little-studied Sufi thinkers of fourteenth-century Cairo. Muhammad Wafā' and his son ‘Alī were poets and mystical philosophers. They founded a new branch of the Shādhiliyya Sufi order, and their descendants went on to become one of the most important families in Egypt. The numerous writings of this father and son, in the tradition of Muhy al-Dīn Ibn ‘Arabī, have as yet received little attention from scholars of Islamic thought. This study introduces these thinkers and surveys their extant writings, almost all of which remain in manuscript form. Beyond describing the contents, the article also seeks to position their thought within the wider context of Islamic mysticism.
Rationed Care: Assessing the Support Needs of Informal
Carers in English Social Services Authorities
Authors: ARKSEY HILARY
Published: October 2002

The passing of the Carers (Recognition and Services Act) 1995 was a step
forward in trying to ensure that people who provide informal care to disabled,
sick or elderly relatives or friends are properly recognised and properly
supported. The Carers Act gave informal carers the right to an
assessment of their own needs, and this article is based on a study into
the impact of the legislation in four local authority social services departments.
It is argued that the vision of supporters of the Carers Act, namely
to achieve real benefits for many carers, has yet to be realised. The analysis
draws on Klein et al.’s (1996) framework of service rationing strategies
to demonstrate that decisions about priority setting and different forms of
rationing of social care took place at three different levels: national government,
local authority and front-line practitioner. Evidence is presented
to show that some carers chose to impose rationing on themselves
by reducing their demands. The article concludes with comments on the
implications of rationing decisions for policy and practice.
NUMBER ONE HUNDRED AND TWENTY ONE May to July 2001
Authors: BENNETT FRAN
Published: October 2002

Contents

1 Social security and income maintenance

2 Health (formerly Health care)

3 Education

4 Housing and environment

5 Personal social services

6 Law and the treatment of the offender

7 Unemployment and the labour market

8 Race relations

9 The voluntary sector

10 Government (formerly Local government)

11 Gender

12 Demography
Perceptions of marriage in late-eighteenth-century Malta
Authors: CIAPPARA FRANS
Published: October 2002

Although the Catholic Church claimed to control marriage, in late-eighteenth-century Malta the faithful still considered matrimony to be a personal affair. The study is based upon episcopal court records and parish registers, which reveal substantial numbers of clandestine marriages, contravening the Council of Trent's directives concerning entry into marriage. Couples separated from each other at will, without the Church's consent. A few took other partners, despite the inquisitors' nets. Couples viewed sexual relations as matters for themselves to regulate, and sex outside marriage as not something into which the Church was to intrude. Especially noteworthy in this respect were relations between betrothed, since a man would not marry a woman who could not bear children.
To breastfeed another woman's child: wet-nursing in Stockholm, 1777–1937
Authors: HEDENBORG SUSANNA
Published: October 2002

The conflict between work and taking care of infants can be solved in many ways. Less than 100 years ago, one of the solutions was the wet-nursing system. This system came to an end at the beginning of the twentieth century. Previous research has connected the cessation to decreasing demand. Here it is argued that to understand the wet-nursing system and to explain its coming to an end, the labour market for women has to be considered. It is necessary to study the supply side of the system: to discover why women became wet-nurses.
Work and wages at Durham Priory and its estates, 1494–1519
Authors: NEWMAN CHRISTINE M.
Published: October 2002

This article explores aspects of employment on the Durham Priory estates in the years 1494–1519. From a perspective of prices and wages, this period belongs at the tail end of a Golden Age for labour. Employment opportunities for the priory workforce should, therefore, have been relatively plentiful and remuneratively rewarding. However, as an analysis of the priory's accounts reveals, whilst wage rates remained stable, the waged employment offered was irregular and piecemeal for all but a small, predominantly skilled elite, with the majority of the workforce enjoying little in the way of fixed employment patterns or identifiable career structures.
Mao's Chair: Revolutionizing Chinese Theatre
Authors: Ruru Li
Published: October 2002

Using rarely seen minutes, manuscripts and photographs preserved in the Shanghai Jingju Theatre archive, an analysis of Interrogating the Chair, a revolutionary Chinese opera embodying Mao's instruction ‘We should never forget the class struggle’, reveals how the ideological demands of the mid-1960s interfered with Chinese theatre. Further, the many revisions of the opera show how the traditional jingju repertoire was transformed into model opera. Interviews with those involved at the time are used to present a direct account of how practitioners dealt with the dilemma of presenting a revolutionary and contemporary theme while keeping faith with their indigenous theatrical form.
Twentieth-Century Fox: Volpone's Metamorphosis
Authors: Shaughnessy Robert
Published: October 2002

Since it was restored to the English theatre during the 1930s, Volpone has enjoyed a unique currency amongst Ben Jonson's works; it has had a more consistent and successful performance history than any other of his plays. Although its beast fable scheme has apparently rendered it more immediately accessible (and allegedly more universal) than the author's humours comedies, it has also provoked responses of ambivalence and unease, in that its coupling of the animal and the human actively unsettles the ethical relations between nature, culture, economics and morality that the allegory ostensibly intends to clarify. In performance, the play has given rise to a critical discourse of vituperation, deviance and excess which reflects the tensions and contradictions endemic to the cultural vocabulary of anthropomorphism. Theatre practice has dealt with the play's problems and provocations by incorporating the image of the animal into an inclusive, consensual and predominantly realist mode of characterization and mise en scène. A notable exception was in 1968, when Tyrone Guthrie directed a production for the National Theatre at the Old Vic which literalized animal identities to the point of excess. The result was a radically contradictory rethinking of the play, and of the performance vocabularies which have been, and can be, deployed to animate it.
A Silent Theatrical Production Representing a Speaking Fictional World: Analysis of A Fleeting Shadow
Authors: Rozik Eli
Published: October 2002

The twentieth-century avant-garde sought to create a theatre dominated, not by language, but by stage images. Is a performance, based solely on speechless images and adopting the style of silent movies, capable of describing a complex fictional world? A superficial study of such movies reveals that even these do not represent silent fictional worlds. On the contrary, their silent frames are meant to evoke verbal interaction, too. This study suggests seven principles, which account for the fact that a speechless theatre production, A Fleeting Shadow (The Khan Theatre, Jerusalem, 1999), despite utter complexity, was fully understood and warmly received by critics and public.
Environmentalists split over Kyoto and Amazonian deforestation
Authors: Fearnside Philip M.
Published: October 2002

Controversies over tropical forest and Kyoto

Slowing deforestation in Amazonia would be a significant contribution to combating global warming and, depending on decisions under the Kyoto Protocol, could provide non-destructive support for rural population in the region (Fearnside 2000a). Crediting avoided deforestation is divisive, both within and among environmental non-governmental organizations (NGOs) and governments. Positions of NGOs on inclusion of avoided deforestation in the Kyoto Protocol's Clean Development Mechanism (CDM) are tightly linked to geography: European NGOs oppose inclusion of forests, USA NGOs (other than USA branches or affiliates of international groups) favour inclusion of forests, and Brazilian NGOs (also excepting most branches or affiliates of international NGOs) also favour forests. The probability of chance explaining these views being clustered in Europe, North America and Brazil in this way is miniscule. In other words, these positions are based on something other than the universal concerns about climate change and future generations that predominate in public statements on all sides.
Monitoring selected indicators of ecological change in the Elbe River since the fall of the Iron Curtain
Authors: Adams Michael S. , Ballin Uta , Gaumert Thomas , Hale Brack W. , Kausch Hartmut , Kruse Reinhard
Published: October 2002

The sudden, large-scale cessation of industrial and agricultural practices following the collapse of the communist regimes in the former Czechoslovakia and East Germany, coupled with a set of programmes aimed at reducing industrial and municipal pollutant loads, provided an unique opportunity to observe changes in a severely polluted river, the Elbe. Several sets of data for the post-communist Elbe reflect water quality and ecological health, including surface water pollutants, accumulation in mussels and several species of fish, and diversity of fish species. The ecological health of the Elbe has indeed benefited, and greatly, from post-communist change. The loads of most pollutants in the Elbe surface water have declined significantly over the last decade. Contaminant loading in fish tissue is also declining. Finally, the diversity of fish species in the Elbe is increasing, with a majority of the returning species being native fishes, characteristic of the pre-World War Two Elbe. Nonetheless, several pollutants remain a concern, including nitrate, suspended sediments, mercury, cadmium, hexachlorobenzene, two DDT metabolites, and three HCH isomers. The reasons for these problems include relicts from the communist era and current activities in the Elbe watershed. Further, the invasion of the river by exotic species, while not yet a concern, does remain a threat.
Isotype specific ELISAs to detect antibodies against swine vesicular disease virus and their use in epidemiology
Authors: DEKKER A. , VAN HEMERT-KLUITENBERG F. , BAARS C. , TERPSTRA C.
Published: October 2002

Isotype specific ELISAs to detect antibodies against swine vesicular disease, which may help to estimate the moment of infection, were developed and validated on sera from pigs experimentally infected with four different isolates of swine vesicular disease virus. Virus specific IgM antibodies could be detected from days 3–49 and occasionally up to day 91 after infection. IgG1 antibodies were first detected at day 8 and IgG2 at day 11. IgA antibodies coincided with IgG1 antibodies, but antibody titres varied widely. From the results obtained with the sera from the experimentally infected pigs, we calculated the day at which 50% of the pigs had become positive (D50). A D50 of 5, 4, 12, 12 and 24 days was calculated, respectively, for the appearance of antibodies in the virus neutralization test, the IgM, total IgG, IgG1 and IgG2 ELISA. A D50 of 49 days was calculated for the disappearance of IgM antibodies. The isotype specific ELISAs proved to be valuable tools to study the epidemiology of the disease.
Within- and between-pen transmission of Classical Swine Fever Virus: a new method to estimate the basic reproduction ratio from transmission experiments
Authors: KLINKENBERG D. , DE BREE J. , LAEVENS H. , DE JONG M. C. M.
Published: October 2002

We present a method to estimate basic reproduction ratio R0 from transmission experiments. By using previously published data of experiments with Classical Swine Fever Virus more extensively, we obtained smaller confidence intervals than the martingale method used in the original papers. Moreover, our method allows simultaneous estimation of a reproduction ratio within pens R0w and a modified reproduction ratio between pens R′0b. Resulting estimates of R0w and R′0b
for weaner pigs were 100 (95% CI 54·4–186) and 7·77 (4·68–12·9), respectively. For slaughter pigs they were 15·5 (6·20–38·7) and 3·39 (1·54–7·45), respectively. We believe, because of the smaller confidence intervals we were able to obtain, that the method presented here is better suited for use in future experiments.
The molecular epidemiology of tuberculosis in inner London
Authors: HAYWARD A. C. , GOSS S. , DROBNIEWSKI F. , SAUNDERS N. , SHAW R. J. , GOYAL M. , SWAN A. , UTTLEY A. , POZNIAK A. , GRACE-PARKER J. , WATSON J. M.
Published: October 2002

The study used DNA fingerprint typing (spoligotyping and Heminested-Inverse-PCR) of Mycobacterium tuberculosis from all culture-confirmed inner London patients over a 12-month period to describe transmission. The methodology was evaluated by comparison with standard IS6110 typing and by examining its ability to identify known household clusters of cases. Isolates sharing indistinguishable typing patterns using both techniques were defined as clustered. Clusters were investigated to identify epidemiological links. The methodology showed good discriminatory power and identified known household clusters of cases. Of 694 culture-confirmed cases, 563 (81%) were typed. Eleven (2%) were due to laboratory cross-contamination and were excluded. Of the remaining 552 isolates 148 (27%) were clustered. Multivariate analysis indicated that clustering was more common in those with pulmonary smear positive disease (P<0·02); those born in the United Kingdom (P<0·0003) and in patients living in south London (P = 0·02). There was also a trend towards clustering being more common in those not known to have HIV infection (P = 0·051). The results suggest that in inner London, recent local transmission makes an important contribution to notification rates.
Incidence and molecular analysis of Vibrio cholerae associated with cholera outbreak subsequent to the super cyclone in Orissa, India
Authors: CHHOTRAY G. P. , PAL B. B. , KHUNTIA H. K. , CHOWDHURY N. R. , CHAKRABORTY S. , YAMASAKI S. , RAMAMURTHY T. , TAKEDA Y. , BHATTACHARYA S. K. , BALAKRISH NAIR G.
Published: October 2002

An epidemiological study was carried out to find out the aetiological agent for diarrhoeal disorders in the cyclone and flood affected areas of Orissa, India. Rectal swabs collected from 107 hospitalized diarrhoea patients were bacteriologically analysed to isolate and identify the various enteropathogens. Detection of toxic genes among E. coli and V. cholerae was carried out by polymerase chain reaction (PCR) assay. Of the 107 rectal swabs analysed, 72·3% were positive for V. cholerae O1 Ogawa, 7·2% for V. cholerae O139, 1·2% for E. coli (EAggEC) and 1·2% for Shigella flexneri type 6. Using multiplex PCR assay it was found that all V. cholerae isolates were ctxA positive and El Tor biotype. Strains of V. cholerae O1 were observed to be resistant to nalidixic acid, furazolidone, streptomycin, co-trimoxazole and ampicillin. Except for nalidixic acid, the resistance pattern for O139 was identical to that of O1 strains. Representative strains of V. cholerae were further characterized by randomly amplified polymorphic DNA (RAPD) analysis and ribotyping. Both O1 and O139 V. cholerae strains exhibited the R3 pattern of ribotype and belonged to a similar pattern of RAPD compared with that of Calcutta strains. Early bacteriological and epidemiological investigations have revealed the dominance of V. cholerae O1 among the hospitalized patients in cyclone affected areas of Orissa. Drinking water scarcity and poor sanitation were thought to be responsible for these diarrhoeal outbreaks. Timely reporting and implementation of appropriate control measures could contain a vital epidemic in this area.
Why are children born to teen mothers at risk for adverse outcomes in young adulthood?
Results from a 20-year longitudinal study
Authors: JAFFEE SARA , CASPI AVSHALOM , MOFFITT TERRIE E. , BELSKY JAY , SILVA PHIL
Published: October 2002

This 20-year longitudinal study showed that the young adult offspring of teen mothers are at
risk for a range of adverse outcomes including early school leaving, unemployment, early
parenthood, and violent offending. We tested how much the effect of teen childbearing on
offspring outcomes could be accounted for by social selection (in which a woman's
characteristics that make her an inadequate parent also make her likely to bear children in her
teens) versus social influence (in which the consequences of becoming a teen mother also bring
harm to her children, apart from any characteristics of her own). The results provided support for
both mechanisms. Across outcomes, maternal characteristics and family circumstances together
accounted for approximately 39% of the effect of teen childbearing on offspring outcomes.
Consistent with a social-selection hypothesis, maternal characteristics accounted for
approximately 18% of the effect of teen childbearing on offspring outcomes; consistent
with a social-influence hypothesis, family circumstances accounted for 21% of the teen
childbearing effect after controlling for maternal characteristics. These results suggest that public
policy initiatives should be targeted not only at delaying childbearing in the population but at
supporting individual at-risk mothers and their children.
Object relations as a predictor of adjustment in conjugal bereavement
Authors: FIELD NIGEL P. , STURGEON SHEILA E. , PURYEAR RICHARD , HIBBARD STEVEN , HOROWITZ MARDI J.
Published: October 2002

The impact of object relations on adjustment in conjugal bereavement was examined. At
approximately 6 months postbereavement, 46 midlife bereaved participants engaged in a narrative
interview in which they were asked to discuss their past relationship with their deceased spouse.
The Westen et al. object relations scoring system was applied to these narratives. Participants also
completed depression and grief-specific symptom measures at 6 months and again at 14 and 25
months postbereavement. Object relations correlated differently with grief-specific symptoms and
depression; it was more strongly negatively associated with 6 month postloss grief-specific
symptoms while more strongly negatively correlated with depression at 25 month postloss. In a
growth curve analysis, more mature object relations was also predictive of a faster rate of
decrease in depression over time. The results were discussed in terms of current theoretical
perspectives on what is required in successful adaptation to conjugal bereavement.
Introduction: music and urban history
Authors: Harding Vanessa
Published: October 2002

Music – as many of the contributors to this special issue of Urban History point out – is an important component of the urban experience and can play a significant role in the construction of a civic identity, and yet it is a topic that urban historians have tended to overlook. There are some parallels with the case of the fine arts, to which a special issue of this journal was devoted in 1995, both in the causes for this neglect – which similarly include ‘the intimidating traditions of connoisseurship associated with the field’ and the difficulty we have with analysing the ‘aesthetic experience’ – and in the developments which are helping to overcome such inhibitions. So far, the impulse seems to be coming from musicologists and music historians, who, inhabiting a fairly small corner of the academic field, are fully conscious of the need to forge connections with other disciplines and historiographical traditions. The importance of contextualizing and historicizing not only the composition but also the production, transmission and reception of music has been recognized for some time, but so far urban historians have not responded as perhaps the music historians thought they might to the insights and openings that a musical ‘new historicism’ seems to offer. But there is clearly an opportunity – indeed, a pressing need – to develop a broadly-based cultural history of towns and cities in which music will take its place. The aim of this special issue is to promote that objective by illustrating the state of the art and suggesting some of the ideas, tools and methodologies with which it might be developed in future.
The sound of silence: models for an urban musicology
Authors: Carter Tim
Published: October 2002

This discussion seeks to provide a context for the emergence of so-called ‘urban musicology’, both within nineteenth-century antiquarian endeavour and in response to scholarly trends in the 1970s and 1980s. The strengths, weaknesses and possible future directions of ‘urban musicology’ are also identified.
Musicians at Laon cathedral in the early fifteenth century
Authors: Plumley Yolanda
Published: October 2002

The city of Laon was a significant commercial and administrative centre in late medieval northern France. Laon's rich and powerful cathedral attracted many to its chapter, which was the largest in the country. In the years circa 1400 its ranks included a number of leading musicians. An investigation into their musical and non-musical duties sheds fascinating light on to the daily life of the cathedral musician and his position in the local urban and rural context.
Cacophony, or vile scrapers on vile instruments: bad music in early modern English towns
Authors: Cockayne Emily
Published: October 2002

Drawing on contemporary musings and references from a variety of civic records, this article will consider music heard in the public spaces of urban England between the mid-sixteenth and mid-eighteenth centuries. Negative reactions to performers such as common fiddlers and street traders became increasingly common as the period progressed and were intimately connected both with fears concerning the crowd-gathering potential of such people and with a desire to control the sound environment to enable effective sleep, worship and concentration.
Regional variation in P2 receptor expression in the rat pulmonary arterial circulation
Authors: Chootip K , Ness K F , Wang Y , Gurney A M , Kennedy C
Published: October 2002

The P2 receptors that mediate contraction of the rat isolated small (SPA, 200–500 μm i.d.) and large (LPA, 1–1.5 mM i.d.) intrapulmonary arteries were characterized.

In endothelium‐denuded vessels the contractile order of potency was α,β‐methyleneATP (α,β‐meATP)>>UDP=UTP=ATP=2‐methylthioATP>ADP in the SPA and α,β‐meATP=UTPUDP>2‐methylthioATP, ATP>>ADP in the LPA. α,β‐meATP, 2‐methylthioATP and ATP had significantly greater effects in the SPA than the LPA (P<0.001), but there was no difference in the potency of UTP or UDP between the vessels.

In the SPA, P2X1 receptor desensitisation by α,β‐meATP (100 μM) inhibited contractions to α,β‐meATP (10 nM–300 μM), but not those to UTP or UDP (100 nM–300 μM). In the LPA, prolonged exposure to α,β‐meATP (100 μM) did not desensitize P2X receptors.

Pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulphonic acid (PPADS), suramin and reactive blue 2 (RB2) (30–300 μM) inhibited contractions evoked by α,β‐meATP. UTP and UDP were potentiated by PPADS, unaffected by RB2 and inhibited, but not abolished by suramin. 1 and 3 mM suramin produced no further inhibition, indicating suramin‐resistant components in the responses to UTP and UDP.

Thus, both P2X and P2Y receptors mediate contraction of rat large and small intrapulmonary arteries. P2Y agonist potency and sensitivity to antagonists were similar in small and large vessels, but P2X agonists were more potent in small arteries. This indicates differential expression of P2X, but not P2Y receptors along the pulmonary arterial tree.

British Journal of Pharmacology (2002) 137, 637–646. doi:10.1038/sj.bjp.0704915
The Na‐K‐ATPase is a target for an EDHF displaying characteristics similar to potassium ions in the porcine renal interlobar artery
Authors: Büssemaker Eckhart , Wallner Christian , Fisslthaler Beate , Fleming Ingrid
Published: October 2002

The present study was performed to determine the characteristics of the endothelium‐derived hyperpolarizing factor (EDHF) that mediates the nitric oxide (NO)‐ and prostacyclin (PGI2)‐independent hyperpolarization and relaxation of porcine renal interlobar arteries.

Bradykinin‐induced changes in isometric force or smooth muscle membrane potential were assessed in rings of porcine renal interlobar artery preconstricted with the thromboxane analogue U46619 in the continuous presence of Nω‐nitro‐L‐arginine and diclofenac to inhibit NO synthases and cyclo‐oxygenases.

Inhibition of NO‐ and PGI2‐production induced a rightward shift in the concentration‐relaxation curve to bradykinin without affecting maximal relaxation. EDHF‐mediated relaxation was abolished by a depolarizing concentration of KCl (40 mM) as well as by a combination of charybdotoxin and apamin (each 100 nM), two inhibitors of calcium‐dependent K+ (K+Ca) channels. Charybdotoxin and apamin also reduced the bradykinin‐induced, EDHF‐mediated hyperpolarization of smooth muscle cells from 13.7±1.3 mV to 5.7±1.2 mV.

In addition to the ubiquitous α1 subunit of the Na‐K‐ATPase, the interlobar artery expressed the γ subunit as well as the ouabain‐sensitive α2, α3 subunits. A low concentration of ouabain (100 nM) abolished the EDHF‐mediated relaxation and reduced the bradykinin‐induced hyperpolarization of smooth muscle cells (13.6±2.8 mV versus 5.20±1.39 mV in the absence and presence of ouabain).

Chelation of K+, using cryptate 2.2.2., inhibited EDHF‐mediated relaxation, without affecting NO‐mediated responses. Elevating extracellular KCl (from 4 to 14 mM) elicited a transient, ouabain‐sensitive hyperpolarization and relaxation that was endothelium‐independent and insensitive to charybdotoxin and apamin.

These results indicate that in the renal interlobar artery, EDHF‐mediated responses display the pharmacological characteristics of K+ ions released from endothelial K+Ca channels. Smooth muscle cell hyperpolarization and relaxation appear to be dependent on the activation of highly ouabain‐sensitive subunits of the Na‐K‐ATPase.

British Journal of Pharmacology (2002) 137, 647–654. doi:10.1038/sj.bjp.0704919
Calmodulin increases transmitter release by mobilizing quanta at the frog motor nerve terminal
Authors: Brailoiu Eugen , Miyamoto Michael D , Dun Nae J
Published: October 2002

The role of calmodulin (CaM) in transmitter release was investigated using liposomes to deliver CaM and monoclonal antibodies against CaM (antiCaM) directly into the frog motor nerve terminal.

Miniature endplate potentials (MEPPs) were recorded in a high K+ solution, and effects on transmitter release were monitored using estimates of the quantal release parameters m (number of quanta released), n (number of functional transmitter release sites), p (mean probability of release), and vars p (spatial variance in p).

Administration of CaM, but not heat‐inactivated CaM, encapsulated in liposomes (1000 units ml−1) produced an increase in m (25%) that was due to an increase in n. MEPP amplitude was not altered by CaM.

Administration of antiCaM, but not heat‐inactivated antiCaM, in liposomes (50 μl ml−1) produced a progressive decrease in m (40%) that was associated with decreases in n and p. MEPP amplitude was decreased (15%) after a 25 min lag time, suggesting a separation in time between the decreases in quantal release and quantal size.

Bath application of the membrane‐permeable CaM antagonist W7 (28 μM) produced a gradual decrease in m (25%) that was associated with a decrease in n. W7 also produced a decrease in MEPP amplitude that paralleled the decrease in m. The decreases in MEPP size and m produced by W7 were both reversed by addition of CaM.

Our results suggest that CaM increases transmitter release by mobilizing synaptic vesicles at the frog motor nerve terminal.

British Journal of Pharmacology (2002) 137, 719–727. doi:10.1038/sj.bjp.0704923
Direct interactions between PSD-95 and stargazin control synaptic AMPA receptor number
Authors: Schnell Eric , Sizemore Max , Karimzadegan Siavash , Chen Lu , Bredt David S. , Nicoll Roger A.
Published: October 2002

Excitatory synapses in the brain exhibit a remarkable degree of functional plasticity, which largely reflects changes in the number of synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). However, mechanisms involved in recruiting AMPARs to synapses are unknown. Here we use hippocampal slice cultures and biolistic gene transfections to study the targeting of AMPARs to synapses. We show that AMPARs are localized to synapses through direct binding of the first two PDZ domains of synaptic PSD-95 (postsynaptic density protein of 95 kDa) to the AMPAR-associated protein, stargazin. Increasing the level of synaptic PSD-95 recruits new AMPARs to synapses without changing the number of surface AMPARs. At the same time, we show that stargazin overexpression drastically increases the number of extra-synaptic AMPARs, but fails to alter synaptic currents if synaptic PSD-95 levels are kept constant. Finally, we make compensatory mutations to both PSD-95 and stargazin to demonstrate the central role of direct interactions between them in determining the number of synaptic AMPARs.
A two-state kinetic model for the unfolding of single molecules by mechanical force
Authors: Ritort F. , Bustamante C. , Tinoco I.
Published: October 2002

We investigate the work dissipated during the irreversible unfolding of single molecules by mechanical force, using the simplest model necessary to represent experimental data. The model consists of two levels (folded and unfolded states) separated by an intermediate barrier. We compute the probability distribution for the dissipated work and give analytical expressions for the average and variance of the distribution. To first order, the amount of dissipated work is directly proportional to the rate of application of force (the loading rate) and to the relaxation time of the molecule. The model yields estimates for parameters that characterize the unfolding kinetics under force in agreement with those obtained in recent experimental results. We obtain a general equation for the minimum number of repeated experiments needed to obtain an equilibrium free energy, to within
k
B
T
, from nonequilibrium experiments by using the Jarzynski formula. The number of irreversible experiments grows exponentially with the ratio of the average dissipated work,
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to
k
B
T.
A conserved flavin-shielding residue regulates NO synthase electron transfer and nicotinamide coenzyme specificity
Authors: Adak Subrata , Sharma Manisha , Meade Abigail L. , Stuehr Dennis J.
Published: October 2002

Nitric oxide synthases (NOSs) are flavoheme enzymes that contain a ferredoxin:NADP
+
-reductase (FNR) module for binding NADPH and FAD and are unusual because their electron transfer reactions are controlled by the Ca
2+
-binding protein calmodulin. A conserved aromatic residue in the FNR module of NOS shields the isoalloxazine ring of FAD and is known to regulate NADPH binding affinity and specificity in related flavoproteins. We mutated Phe-1395 (F1395) in neuronal NOS to Tyr and Ser and tested their effects on nucleotide coenzyme specificity, catalytic activities, and electron transfer in the absence or presence of calmodulin. We found that the aromatic side chain of F1395 controls binding specificity with respect to NADH but does not greatly affect affinity for NADPH. Measures of flavin and heme reduction kinetics, ferricyanide and cytochrome
c
reduction, and NO synthesis established that the aromatic side chain of F1395 is required to repress electron transfer into and out of the flavins of neuronal NOS in the calmodulin-free state, and is also required for calmodulin to fully relieve this repression. We speculate that the phenyl side chain of F1395 is part of a conformational trigger mechanism that negatively or positively controls NOS electron transfer depending on the presence of calmodulin. Such use of the conserved aromatic residue broadens our understanding of flavoprotein structure and regulation.
Pathogenic and nonpathogenic hantaviruses differentially regulate endothelial cell responses
Authors: Geimonen Erika , Neff Sherry , Raymond Tracy , Kocer Salih S. , Gavrilovskaya Irina N. , Mackow Erich R.
Published: October 2002

Hantaviruses cause two human diseases: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Hantaviruses infect human endothelial cells but cause little or no damage to the infected endothelium. We analyzed with Affymetrix DNA Arrays (Santa Clara, CA) the endothelial cell transcriptional responses directed by hantaviruses associated with HPS [New York-1 virus (NY-1V)], HFRS [Hantaan virus (HTNV)], or by a hantavirus not associated with human disease [Prospect Hill virus (PHV)]. Hantavirus infections induced 117 cellular genes and repressed 25 genes by >3-fold, 4 days postinfection (p.i.). Although >80% of cells were infected by each virus 1 day p.i., PHV induced or repressed 67 genes at this early time compared with three genes altered by HTNV or NY-1V. The early high-level induction of 24 IFN-stimulated genes by PHV (4- to 229-fold) represents a fundamental difference in the temporal regulation of cellular responses by pathogenic and nonpathogenic hantaviruses. Because all hantaviruses induced >23 IFN-stimulated genes at late times p.i., pathogenic hantaviruses appear to suppress early cellular IFN responses that are activated by nonpathogenic hantaviruses. At late times p.i., 13 genes were commonly induced by HTNV and NY-1V that were not induced by PHV. In contrast to NY-1V, HTNV uniquely induced a variety of chemokines and cell adhesion molecules (i.e., IL-8, IL-6, GRO-β, ICAM), as well as two complement cascade-associated factors that may contribute to immune components of HFRS disease. NY-1V failed to induce most cellular chemokines directed by HTNV (3/14) or genes primarily activated by NF-κB. However, NY-1V uniquely induced β3 integrin-linked potassium channels, which could play a role in HPS-associated vascular permeability. These studies provide a basic understanding of hantavirus-directed cellular responses that are likely to differentiate pathogenic and nonpathogenic hantaviruses, contribute to HFRS and HPS pathogenesis, and provide insight into disease mechanisms and potential therapeutic interventions.
An activation domain in the C-terminal subunit of HCF-1 is important for transactivation by VP16 and LZIP
Authors: Luciano Randy L. , Wilson Angus C.
Published: October 2002

In herpes simplex virus, lytic replication is initiated by the viral transactivator VP16 acting with cellular cofactors Oct-1 and HCF-1. Although this activator complex has been studied in detail, the role of HCF-1 remains elusive. Here, we show that HCF-1 contains an activation domain (HCF-1
AD
) required for maximal transactivation by VP16 and its cellular counterpart LZIP. Expression of the VP16 cofactor p300 augments HCF-1
AD
activity, suggesting a mechanism of synergy. Infection of cells lacking the HCF-1
AD
leads to reduced viral immediate-early gene expression and lowered viral titers. These findings underscore the importance of HCF-1 to herpes simplex virus replication and VP16 transactivation.
Electrical cues regulate the orientation and frequency of cell division and the rate of wound healing
in
vivo
Authors: Song Bing , Zhao Min , Forrester John V. , McCaig Colin D.
Published: October 2002

Controlling cell division is fundamental. One environmental cue that exerts profound control over both the orientation and frequency of cell division
in vivo
is a naturally occurring, wound-induced electric field (EF). Wounds in rat corneas generate endogenous EFs in the plane of the epithelial sheet because the transcorneal potential difference (TCPD; +40 mV internally positive) collapses at the wound edge, but is maintained at normal levels at 0.5 mm back from the wound. We manipulated the endogenous EF this creates by using drugs with differing actions. The wound-induced EF controlled the orientation of cell division; most epithelial cells divided with a cleavage plane parallel to the wound edge and perpendicular to the EF vector. Increasing or decreasing the EF pharmacologically, respectively increased or decreased the extent of oriented cell division. In addition, cells closest to the wound edge, where the EF was highest, were oriented most strongly by the EF. Remarkably, an endogenous EF also enhanced the frequency of cell division. This also was regulated by enhancing or suppressing the EF pharmacologically. Because the endogenous EF also regulated the wound healing rate, it may act as one control of the interplay between cell migration and cell division during healing.
Protonation of non-Watson–Crick base pairs and encapsidation of turnip yellow mosaic virus RNA
Authors: Bink Hugo H. J. , Hellendoorn Koen , van der Meulen Jannes , Pleij Cornelis W. A.
Published: October 2002

The 5′ UTR of turnip yellow mosaic virus RNA contains two conserved hairpins with internal loops consisting of C⋅C and C⋅A mismatches. In this article, evidence is presented indicating that the 5′ proximal hairpin functions as an encapsidation initiation signal. Extensive mutagenesis studies on this hairpin and sequencing of virus progeny showed a clear preference for C⋅C and C⋅A mismatches within the internal loop. The importance of these mismatches lies in their pH-dependent protonation and stable base pair formation. Encapsidation efficiency was found to be severely affected for several mutants lacking the protonatable mismatches in the internal loop of the 5′ proximal hairpin. Furthermore, gel mobility-shift assays were performed with various RNA hairpins and empty capsids with a hole. Protonatable hairpins containing C⋅C and/or C⋅A pairs were found to bind specifically to the interior of the protein shell under acidic conditions (pH 4.5) in the presence of spermidine. Based on these results we propose that this binding of protonated cytosines to the coat protein of turnip yellow mosaic virus may represent a new motif in RNA–protein interactions.
Two regulatory levels of transcriptional gene silencing in
Arabidopsis
Authors: Scheid Ortrun Mittelsten , Probst Aline V. , Afsar Karin , Paszkowski Jerzy
Published: October 2002

In mammals, some fungi, and plants, DNA methylation plays a central role in the epigenetic control of gene transcription. Recently, however, a subclass of
Arabidopsis
mutants revealed that the release of transcriptional gene silencing (TGS) does not necessarily require DNA demethylation. Here, we address the fundamental question of whether these mutants delineate a previously uncharacterized, methylation-independent level of epigenetic regulation, or whether they just act downstream of DNA methylation signals. Two mutants described earlier,
ddm1
and
mom1
, reactivate previously silent loci:
ddm1
impairs TGS by reducing chromosomal DNA methylation, and
mom1
releases TGS without affecting DNA methylation. We examined the epistatic relationship between
ddm1
and
mom1
by constructing double mutant strains. The synergistic release of TGS revealed by gene expression patterns from silent loci, drastic developmental abnormalities, and characteristic changes in nuclear architecture in these double mutants implies that DDM1 and MOM are likely to operate at independent levels in TGS control. Our results indicate that the methylation-independent silencing mechanism reinforces the methylation-based system and prevents extremely rapid epigenetic deregulation in plants with DNA methylation deficiencies.
Suppression of lipopolysaccharide-induced antiviral transcription factor (STAT-1 and NF-κB) complexes by antibody-dependent enhancement of macrophage infection by Ross River virus
Authors: Mahalingam Surendran , Lidbury Brett A.
Published: October 2002

Subneutralizing concentrations of antibody may enhance virus infection by bringing the virus–antibody complex into contact with the cell surface Fc receptors; this interaction facilitates entry of virus into the cell and is referred to as antibody-dependent enhancement (ADE) of infection. Northern analysis of macrophage RNA demonstrated that ADE infection by the indigenous Australian alphavirus Ross River (RRV-ADE) ablated or diminished message for tumor necrosis factor α (TNF-α), nitric-oxide synthase 2 (NOS2), and IFN regulatory factor 1 (IRF-1), as well as for IFN-inducible protein 10 (IP-10) and IFN-β; the transcription of a control gene was unaffected. Additionally, electrophoretic mobility-shift assay (EMSA) studies showed that transcription factor IFN-α-activated factor (AAF), IFN-stimulated gene factor 3 (ISGF3), and nuclear factor-κB (NF-κB) complex formation in macrophage nuclear extracts were specifically suppressed post-RRV-ADE infection, emphasizing the capacity for ADE infections to compromise antiviral responses at the transcriptional level. The suppression of antiviral transcription factor complexes was shown to depend on replicating virus and was not simply a result of general antibody–Fc–receptor interaction. Although only a minority of cells (≈15%) were shown to be positive for RRV by immunostaining techniques post ADE, molecular (RT-PCR) analysis showed that unstained cells carried RRV-RNA, indicating a higher level of viral infectivity than previously suspected. Electron microscopy studies confirmed this observation. Furthermore, levels of cellular IL-10 protein were dramatically elevated in RRV-ADE cultures. This evidence demonstrates that RRV can potently disrupt the activation of specific antiviral pathways via ADE infection pathways, and may suggest a significant mechanism in the infection and pathogenesis of other ADE viruses.
Structures and stabilities of higher coordinate onium-boronium dications (X
+
BH
3
+
and X
+
BH
5
+
; X = NH
3
, PH
3
, H
2
O, and H
2
S)
Authors: Rasul Golam , Prakash G. K. Surya , Olah George A.
Published: October 2002

Structures of higher coordinate onium-boronium dications (X
+
BH
3
+
1–4a and X
+
BH
5
+
1–4d; X = NH
3
, PH
3
, H
2
O, and H
2
S) were calculated by using the
ab initio
method at the MP2/6-311+G** level. All of the dications 1–4a contain a four-coordinate boron atom with a three-center two-electron bond involving boron and two hydrogens. On the other hand, all the dications 1–4d contain a six-coordinate boron atom with two three-center two-electron bonds. The thermodynamics of the complexations of 1–4a and H
2
to form 1–4d were computed. Deprotonations of 1–4d were found to be substantially endothermic.
Transport of nitrated albumin across continuous vascular endothelium
Authors: Predescu Dan , Predescu Sanda , Malik Asrar B.
Published: October 2002

Because modification of plasma albumin on tyrosine residues generates nitrated albumin (NOA) that may function as a mechanism of nitrogen monoxide clearance from microcirculation, we investigated biochemicaly and morphologically the cell surface binding and the transendothelial transport of NOA. An electron microscopic study was carried out with mouse lungs and hearts perfused
in situ
with NOA and NOA-Au complexes. The results indicate that NOA-Au can bind to the endothelial cell surface, and its binding can be blocked by albumin plus nitrotyrosine (NO-tyrosine) or abolished by excess NOA. We detected NOA-Au into perivascular spaces as early as 30 sec after the beginning of its perfusion. NOA, unlike native albumin, leaves the vascular lumina via both endothelial caveolae and open junctions. By cross-linking and ligand blotting analysis, we showed that NOA interacted with the same albumin binding proteins of 16–18, 30–32, 60, and 74 kDa as native albumin. ELISA performed on tissue homogenates obtained from the same specimens showed that NOA transport was 2- to 4-fold greater than native albumin. The augmented transendothelial transport of NOA reflects its transcytosis as well as its exit from the microcirculation via open junctions. The increased transport of NOA may serve as an important mechanism that protects a vascular bed against the damaging effects of nitrogen monoxide and peroxynitrite.
Overexpression of a pattern-recognition receptor, peptidoglycan-recognition protein-LE, activates imd/relish-mediated antibacterial defense and the prophenoloxidase cascade in
Drosophila
larvae
Authors: Takehana Aya , Katsuyama Tomonori , Yano Tamaki , Oshima Yoshiteru , Takada Haruhiko , Aigaki Toshiro , Kurata Shoichiro
Published: October 2002

In
Drosophila
, microbial infection activates an antimicrobial defense system involving the activation of proteolytic cascades in the hemolymph and intracellular signaling pathways, the immune deficiency (imd) and Toll pathways, in immune-responsive tissues. The mechanisms for microbial recognition are largely unknown. We report that, in larvae, the imd-mediated antibacterial defense is activated by peptidoglycan-recognition protein (PGRP)-LE, a PGRP-family member in
Drosophila
. Consistent with this, PGRP-LE binds to the diaminopimelic acid-type peptidoglycan, a cell-wall component of the bacteria capable of activating the imd pathway, but not to the lysine-type peptidoglycan. Moreover, PGRP-LE activates the prophenoloxidase cascade, a proteolytic cascade in the hemolymph. Therefore, PGRP-LE acts as a pattern-recognition receptor to the diaminopimelic acid-type peptidoglycan and activates both the proteolytic cascade and intracellular signaling in
Drosophila
immunity.