bluuebunny/crossref_metadata_2025 huggingface dataset:
Dominant negative mutant of a lipoprotein‐specific molecular chaperone, LolA, tightly associates with LolCDE
Authors: Miyamoto Atsuki , Matsuyama Shin-ichi , Tokuda Hajime
Published: October 2002

Periplasmic molecular chaperone LolA and the inner membrane ATP binding cassette transporter LolCDE are essential for ATP‐dependent release of outer membrane‐directed lipoproteins from the inner membrane of Escherichia coli. A LolA(F47E) mutant carrying a Phe to Glu mutation at position 47 was defective in the release of lipoproteins from spheroplasts and proteoliposomes reconstituted with LolCDE. When incubated with proteoliposomes containing LolCDE, LolA remained in the supernatant whereas LolA(F47E) bound to proteoliposomes. This tight association of LolA(F47E) with LolCDE caused a dominant negative phenotype in vivo, suggesting that the LolA–LolCDE interaction is critical for lipoprotein release.
Increased stability of human growth hormone with reduced lactogenic potency
Authors: Schulga Alexey A , Makarov Alexander A , Levichkin Iliya V , Belousova Yuliya V , Lobachov Vladimir M , Protasevich Irina I , Pace C.Nick , Kirpichnikov Mikhail P
Published: October 2002

Human growth hormone (hGH), whose main function is the somatic growth stimulation, induces diverse effects including lactation. We examined the possibility of hGH stabilization by elimination of its lactogenic activity. Chimeric GHs were constructed by replacement of different segments of hGH with sequences derived from non‐lactogenic porcine GH. As was observed in the rat Nb2‐11C lymphoma cell test, lactogenic activity of some chimeric hormones was seriously destroyed. This kind of hormones displayed the substantial increase in thermal and guanidine hydrochloride stability. The more stable hGH variants were found to be more soluble in Escherichia coli cells.
Alternative splicing of the rat Cav3.3 T‐type calcium channel gene produces variants with distinct functional properties1
Authors: Murbartián Janet , Arias Juan Manuel , Lee Jung-Ha , Gomora Juan Carlos , Perez-Reyes Edward
Published: October 2002

Molecular diversity in T‐type Ca2+ channels is produced by expression of three genes, and alternative splicing of those genes. Prompted by differences noted between rat and human Cav3.3 sequences, we searched for splice variants. We cloned six variants, which are produced by splicing at exon 33 and exon 34. Expression of the variants differed between brain regions. The electrophysiological properties of the variants displayed similar voltage‐dependent gating, but differed in their kinetic properties. The functional impact of splicing was inter‐related, suggesting an interaction. We conclude that alternative splicing of the Cav3.3 gene produces channels with distinct properties.
Investigating the manufacturing–marketing interface in new product development: does context affect the strength of relationships?
Authors: Calantone Roger , Dröge Cornelia , Vickery Shawnee
Published: October 2002

This study explores the nature of the relationships characterizing the marketing–manufacturing interface in new product development (NPD). Four constructs are examined: (1) marketing’s knowledge of manufacturing; (2) manufacturing’s evaluation of marketing communication; (3) marketing–manufacturing integration; and (4) marketing–manufacturing relationship quality. Knowledge and communication are represented as antecedents of relationship quality and integration in a structural equations model (SEM). All relationships are posited to be positive, and we test whether they are moderated by (1) high versus low environmental uncertainty, and by (2) a high versus low rate of new product introduction as compared to competitors. In all cases but low uncertainty, the majority of structural paths are positive. Nevertheless, a strong, positive link exists between knowledge and integration in the low uncertainty case. Overall, we find that the more marketing knows about manufacturing and the more marketing is able to communicate credibly with manufacturing, better relationships and functional relationships will result with a variety of contingencies notwithstanding.
Ectopic dendrite initiation: CNS pathogenesis as a model of CNS development
Authors: Siegel Donald A. , Huang May K. , Becker Shannon F.
Published: October 2002

The neuronal storage diseases are a rare group of disorders with profound clinical consequences including severe mental retardation and death in early childhood. A subset of these disorders, those with elevated levels of GM2 ganglioside, are further characterized by the reinitiation of primary dendrites on mature cortical neurons. These ectopic dendrites are unusual as primary dendrite initiation is normally confined to a narrow developmental window. Thus, ectopic dendritogenesis appears to be a recapitulation of the normal developmental program temporally displaced. Consequently, understanding ectopic dendritogenesis should offer insights into both the pathogenesis of the neuronal storage diseases as well as mechanisms of normal CNS development.

Using a feline model of GM2 gangliosidosis, we compared patterns of gene expression in normal newborn and mature diseased animals (both undergoing active primary dendritogenesis) with normal, mature controls (where primary dendritogenesis has ceased). From this work, we have identified two genes that appear to function in primary dendrite initiation. One, tomoregulin, is an integral membrane protein with both EGF‐ and follistatin‐like motifs in its extracellular domain. The second, Tristanin, is a member of the positive regulatory domain (PRD) family of a zinc‐finger transcription factors. Both genes are up regulated in the disease state, and both show a shift in their intracellular location to the nucleus in diseased animals that is not observed in age matched controls. In normal mouse brain, tomoregulin and Tristanin reveal developmental patterns consistent with a role in dendrite initiation and show changes in subcellular localization similar to that observed in the cat.
The fallacy of cookie cutter asset allocation
Authors: Spitzer John J. , Singh Sandeep
Published: October 2002

In this paper, we establish why ``prefabricated'' asset allocation schemes mandated by some education savings programs might be suboptimal. Then, using the New York's College Savings Program as an example, we simulate and then compare end of period wealth accumulated in both a tax preferred but regimented asset allocation plan, and in a nontax protected plan.

We find, first, that the longer the child participates in the plan, the greater the bene®t. Second, participants in higher tax brackets derive greater bene®ts; adherence to prespeci®ed asset allocation for low tax bracket investors often results in return loss that overshadows the tax benefit. Copyright 2001 Elsevier Science Inc. All rights reserved.
In the presence of L‐NAME SERCA blockade induces endothelium‐dependent contraction of mouse aorta through activation of smooth muscle prostaglandin H2/thromboxane A2 receptors
Authors: Okon Elena B , Golbabaie Ali , Breemen Cornelis van
Published: October 2002

The mechanism of transient contractions induced by the sarcoplasmic–endoplasmic reticulum calcium ATPase (SERCA) blocker cyclopiazonic acid (CPA) in the presence of L‐NAME was investigated in mouse aorta.

The contractions elicited by 10 μM CPA required an intact endothelium, were dependent upon external Ca2+ and were prevented by 10 μM indomethacin, the inhibitor of prostaglandin synthesis, or 1 μM SQ29548, the specific prostaglandin H2/thromboxane A2 (PGH2/TXA2) receptor blocker.

A blocker of receptor/store operated Ca2+ channels and voltage gated calcium channels (VGCC), SK&F 96365 (10 μM), completely abolished the contractions, while a specific blocker of VGCC nifedipine (1 μM) inhibited them by one third.

Dichlorobenzamyl hydrochloride, a blocker of Na+/Ca2+ exchange effectively prevented return of tension to baseline value.

At higher concentrations (30–100 μM) CPA induced indomethacin‐resistant tonic contractions of mouse aorta. The CPA dose response curve for tonic contractions is shifted to the right compared to the transient contractions suggesting that smooth muscle is less sensitive to CPA than endothelium.

PGH2/TXA2 receptors in mouse aorta are highly sensitive to the thromboxane analogue U46619 (EC50 : 1.93 nM). This compound stimulates contractions even in the absence of external Ca2+, which are abolished by the Rho‐kinase inhibitor HA‐1077.

The results suggest that 10 μM CPA induced capacitive Ca2+ entry in endothelial cells stimulating the release of PGH2/TXA2, which subsequently caused smooth muscle contraction dependent on Ca2+ influx and myofilament sensitization by Rho‐kinase. Higher concentrations of CPA (30–100 μM) directly induced contraction of mouse aortic smooth muscle.

British Journal of Pharmacology (2002) 137, 545–553. doi:10.1038/sj.bjp.0704884
Suppression of basic fibroblast growth factor‐induced angiogenesis by a specific chymase inhibitor, BCEAB, through the chymase‐angiotensin‐dependent pathway in hamster sponge granulomas
Authors: Muramatsu Michiko , Yamada Mayumi , Takai Shinji , Miyazaki Mizuo
Published: October 2002

We investigated the profound involvement of mast cell chymase, an alternative angiotensin II‐generating enzyme, in angiogenesis using a specific chymase inhibitor. We also studied the functional profiles of this novel inhibitor in basic fibroblast growth factor (bFGF)‐induced angiogenesis.

In this study, angiogenesis was induced by daily injections of bFGF (0.3 μg site−1 day−1), angiotensin I (2 nmol site−1 day−1) or angiotensin II (2 nmol site−1 day−1) into sponges implanted to male hamsters subcutaneously for 7 days. Angiogenesis in the granulation tissue surrounding sponges was evaluated by measuring the haemoglobin (Hb) content and local blood flow as the parameters for angiogenesis.

A chymase inhibitor, BCEAB (4‐[1‐{[bis‐(4‐methyl‐phenyl)‐methyl]‐carbamoyl}‐3‐(2‐ethoxy‐benzyl)‐4‐oxo‐azetidine‐2‐yloxy]‐benzoic acid), was simultaneously administered into the implanted sponges (2 or 5 nmol site−1 day−1, for 7 days) treated with bFGF and strongly suppressed the haemoglobin contents in sponge granulomas. In the studies using a laser doppler perfusion imager, BCEAB (5 nmol site−1 day−1) also attenuated the bFGF‐induced increase of local blood flow around the implanted sponge granuloma.

In bFGF‐induced angiogenesis, chymase activity in sponge granulomas was substantially increased. It was also confirmed that the chymase activity increased by bFGF was significantly and dose‐dependently inhibited by BCEAB (2, 5 nmol site−1 day−1).

BCEAB inhibited the Hb contents and the expression of vascular endothelial growth factor (VEGF) mRNA induced by angiotensin I but not by angiotensin II.

These results suggest that the significance of chymase in bFGF‐induced angiogenesis was confirmed, and a novel inhibitor, BCEAB, strongly suppresses the bFGF‐induced angiogenesis through the chymase‐angiotensin II‐VEGF dependent pathway.

British Journal of Pharmacology (2002) 137, 554–560. doi:10.1038/sj.bjp.0704893
Effect of YM‐53601, a novel squalene synthase inhibitor, on the clearance rate of plasma LDL and VLDL in hamsters
Authors: Ugawa Tohru , Kakuta Hirotoshi , Moritani Hiroshi , Inagaki Osamu
Published: October 2002

To better understand how it decreases plasma cholesterol and triglyceride, we evaluated the effect of YM‐53601 ((E‐2‐[2‐fluoro‐2‐(quinuclidin‐3‐ylidene) ethoxy]‐9H‐carbozole monohydrochloride) on the clearance rate of low density lipoprotein (LDL) and very low density lipoprotein (VLDL) in hamsters.

Treatment with YM‐53601 at 50 mg kg−1 for 5 days in hamsters fed a normal diet enhanced the disappearance of 1,1′‐Dioctadecyl‐3,3,3′,3′‐tetramethylindocarbocyanine perchlorate (DiI)‐VLDL and DiI‐LDL. This effect on DiI‐LDL was lost in the early phase after DiI‐methyl(met)‐LDL, chemically modified to block LDL receptor binding, was injected in hamsters, but was retained in the late phase. Pre‐treatment with protamine sulphate, which inhibits the activity of LPL, also failed to enhance DiI‐VLDL clearance rate by YM‐53601.

Even on single oral administration at 30 mg kg−1, YM‐53601 enhanced the disappearance of the high concentration of plasma triglyceride after injection of intrafat, an emulsion of fat. Plasma triglyceride was significantly decreased as soon as 1 h after single administration of YM‐53601 in hamsters fed a normal diet.

These results indicate that the decrease in plasma total cholesterol and triglyceride after the treatment with YM‐53601 is due to its enhancement of the clearance rate of LDL and VLDL, respectively. Moreover, YM‐53601 may be effective in decreasing plasma triglyceride levels early in the course of treatment of hypertriglyceridaemia in humans.

British Journal of Pharmacology (2002) 137, 561–567. doi:10.1038/sj.bjp.0704906
Unfolding of quadruplex structure in the G-rich strand of the minisatellite repeat by the binding protein UP1
Authors: Fukuda Hirokazu , Katahira Masato , Tsuchiya Naoto , Enokizono Yoshiaki , Sugimura Takashi , Nagao Minako , Nakagama Hitoshi
Published: October 2002

The mouse hypervariable minisatellite (MN) Pc-1 consists of tandem repeats of d(GGCAG) and flanked sequences. We have previously demonstrated that single-stranded d(GGCAG)
n
folds into the intramolecular folded-back quadruplex structure under physiological conditions. Because DNA polymerase progression
in vitro
is blocked at the repeat, the characteristic intramolecular quadruplex structure of the repeat, at least in part, could be responsible for the hypermutable feature of Pc-1 and other MNs with similar repetitive units. On the other hand, we have isolated six MN Pc-1 binding proteins (MNBPs) from nuclear extracts of NIH 3T3 cells. Here, we describe one of those MNBPs, MNBP-B, that binds to the single-stranded d(GGCAG)
n
. Amino acid sequences of seven proteolytic peptide fragments of MNBP-B were determined, and the cDNA clones were isolated. MNBP-B was proven identical to the single-stranded DNA-binding protein, UP1. Recombinant UP1 bound to single-stranded d(GGCAG)
n
and other G-rich repetitive sequences, such as d(GTCAGG)
n
and d(GTTAGG)
n
. In addition, UP1 was demonstrated by CD spectrum analysis to unfold the intramolecular quadruplex structure of d(GGCAG)
5
and d(TTAGGG)
4
and to abrogate the arrest of DNA synthesis at the d(GGG)
n
site. This ability of UP1 suggests that unfolding of quadruplex DNA is required for DNA synthesis processes.
Teratogenicity induced by targeting a placental immunoglobulin transporter
Authors: Kolonin Mikhail G. , Pasqualini Renata , Arap Wadih
Published: October 2002

Approximately 3% of children in developed countries are born with nongenetic birth defects. However, the nature and mechanisms of teratogenesis are poorly understood. We investigated mechanisms of teratogen-mediated blockade of maternofetal transport by screening a combinatorial library for peptides that bind nonendothelial placental vasculature in pregnant mice. Here, we identified a peptide motif, TPKTSVT, that homes to the yolk sac, induces placental necrosis, and disrupts embryo development. We show that TPKTSVT promotes transcytosis of phage into the embryo and blocks the transplacental transport of immunoglobulins. Based on these data, we propose a model in which TPKTSVT targets a placental Fc receptor. Absence of TPKTSVT placental homing in mice lacking β2-microglobulin (β2m) suggests FcRn/β2m as a target for the TPKTSVT, which is unexpected, given the normal development of FcRn/β2m-deficient progeny. High-throughput screening for embryotoxins that target placental receptors could be developed to systematically identify and avoid exposure to teratogenic drugs.
The Chapel Hill hemophilia A dog colony exhibits a factor VIII gene inversion
Authors: Lozier Jay N. , Dutra Amalia , Pak Evgenia , Zhou Nan , Zheng Zhili , Nichols Timothy C. , Bellinger Dwight A. , Read Marjorie , Morgan Richard A.
Published: October 2002

In the Chapel Hill colony of factor VIII-deficient dogs, abnormal sequence (
ch8
, for
c
anine
h
emophilia
8
, GenBank no.
AF361485
) follows exons 1–22 in the factor VIII transcript in place of exons 23–26. The canine hemophilia 8 locus (
ch8
) sequence was found in a 140-kb normal dog genomic DNA bacterial artificial chromosome (BAC) clone that was completely outside the factor VIII gene, but not in BAC clones containing the factor VIII gene. The BAC clone that contained
ch8
also contained a homologue of
F8A
(
f
actor
8 a
ssociated) sequence, which participates in a common inversion that causes severe hemophilia A in humans. Fluorescence
in situ
hybridization analysis indicated that exons 1–26 normally proceed sequentially from telomere to centromere at Xq28, and
ch8
is telomeric to the factor VIII gene. The appearance of an “upstream” genomic sequence element (
ch8
) at the end of the aberrant factor VIII transcript suggested that an inversion of genomic DNA replaced factor VIII exons 22–26 with
ch8
. The
F8A
sequence appeared also in overlapping normal BAC clones containing factor VIII sequence. We hypothesized that homologous recombination between copies of canine
F8A
inside and outside the factor VIII gene had occurred, as in human hemophilia A. High-resolution fluorescent
in situ
hybridization on hemophilia A dog DNA revealed a pattern consistent with this inversion mechanism. We also identified a
Hin
dIII restriction fragment length polymorphism of
F8A
fragments that distinguished hemophilia A, carrier, and normal dogs' DNA. The Chapel Hill hemophilia A dog colony therefore replicates the factor VIII gene inversion commonly seen in humans with severe hemophilia A.
Food-web structure and network theory: The role of connectance and size
Authors: Dunne Jennifer A. , Williams Richard J. , Martinez Neo D.
Published: October 2002

Networks from a wide range of physical, biological, and social systems have been recently described as “small-world” and “scale-free.” However, studies disagree whether ecological networks called food webs possess the characteristic path lengths, clustering coefficients, and degree distributions required for membership in these classes of networks. Our analysis suggests that the disagreements are based on selective use of relatively few food webs, as well as analytical decisions that obscure important variability in the data. We analyze a broad range of 16 high-quality food webs, with 25–172 nodes, from a variety of aquatic and terrestrial ecosystems. Food webs generally have much higher complexity, measured as connectance (the fraction of all possible links that are realized in a network), and much smaller size than other networks studied, which have important implications for network topology. Our results resolve prior conflicts by demonstrating that although some food webs have small-world and scale-free structure, most do not if they exceed a relatively low level of connectance. Although food-web degree distributions do not display a universal functional form, observed distributions are systematically related to network connectance and size. Also, although food webs often lack small-world structure because of low clustering, we identify a continuum of real-world networks including food webs whose ratios of observed to random clustering coefficients increase as a power–law function of network size over 7 orders of magnitude. Although food webs are generally not small-world, scale-free networks, food-web topology is consistent with patterns found within those classes of networks.
Structural characterization of the PIT-1/ETS-1 interaction: PIT-1 phosphorylation regulates PIT-1/ETS-1 binding
Authors: Augustijn Kevin D. , Duval Dawn L. , Wechselberger Rainer , Kaptein Rob , Gutierrez-Hartmann Arthur , van der Vliet Peter C.
Published: October 2002

The POU-domain transcription factor Pit-1 and Ets-1, a member of the ETS family of transcription factors, can associate in solution and synergistically activate the prolactin promoter by binding to a composite response element in the prolactin promoter. We mapped the minimal region of Ets-1 required for the interaction with the Pit-1 POU-homeodomain. Here, we describe a detailed NMR study of the interaction between the POU-homeodomain of Pit-1 and the minimal interacting region of Ets-1. By using heteronuclear single quantum coherence titration experiments, we were able to map exact residues on the POU-homeodomain that are involved in the interaction with this minimal Ets-1 interaction domain. By using our NMR data, we generated point mutants in the POU-homeodomain and tested their effect on the interaction with Ets-1. Our results show that phosphorylation of Pit-1 can regulate the interaction with Ets-1.
Modeling dynamic and network heterogeneities in the spread of sexually transmitted diseases
Authors: Eames Ken T. D. , Keeling Matt J.
Published: October 2002

A wide range of communicable human diseases can be considered as spreading through a network of possible transmission routes. The implied network structure is vital in determining disease dynamics, especially when the average number of connections per individual is small as is the case for many sexually transmitted diseases (STDs). Here we develop an intuitive mathematical framework to deal with the heterogeneities implicit within contact networks and those that arise because of the infection process. These models are compared with full stochastic simulations and show excellent agreement across a wide range of parameters. We show how such models can be used to estimate parameters of epidemiological importance, and how they can be extended to examine the effectiveness of various control strategies, in particular screening programs and contact tracing.
Classification of scale-free networks
Authors: Goh Kwang-Il , Oh Eulsik , Jeong Hawoong , Kahng Byungnam , Kim Doochul
Published: October 2002

While the emergence of a power-law degree distribution in complex networks is intriguing, the degree exponent is not universal. Here we show that the betweenness centrality displays a power-law distribution with an exponent η, which is robust, and use it to classify the scale-free networks. We have observed two universality classes with η ≈ 2.2(1) and 2.0, respectively. Real-world networks for the former are the protein-interaction networks, the metabolic networks for eukaryotes and bacteria, and the coauthorship network, and those for the latter one are the Internet, the World Wide Web, and the metabolic networks for Archaea. Distinct features of the mass-distance relation, generic topology of geodesics, and resilience under attack of the two classes are identified. Various model networks also belong to either of the two classes, while their degree exponents are tunable.
A self-replicating ligase ribozyme
Authors: Paul Natasha , Joyce Gerald F.
Published: October 2002

A self-replicating molecule directs the covalent assembly of component molecules to form a product that is of identical composition to the parent. When the newly formed product also is able to direct the assembly of product molecules, the self-replicating system can be termed autocatalytic. A self-replicating system was developed based on a ribozyme that catalyzes the assembly of additional copies of itself through an RNA-catalyzed RNA ligation reaction. The R3C ligase ribozyme was redesigned so that it would ligate two substrates to generate an exact copy of itself, which then would behave in a similar manner. This self-replicating system depends on the catalytic nature of the RNA for the generation of copies. A linear dependence was observed between the initial rate of formation of new copies and the starting concentration of ribozyme, consistent with exponential growth. The autocatalytic rate constant was 0.011 min
−1
, whereas the initial rate of reaction in the absence of pre-existing ribozyme was only 3.3 × 10
−11
M⋅min
−1
. Exponential growth was limited, however, because newly formed ribozyme molecules had greater difficulty forming a productive complex with the two substrates. Further optimization of the system may lead to the sustained exponential growth of ribozymes that undergo self-replication.
Synapse formation is associated with memory storage in the cerebellum
Authors: Kleim Jeffrey A. , Freeman John H. , Bruneau Rochelle , Nolan Brian C. , Cooper Natalie R. , Zook Alison , Walters Drew
Published: October 2002

The idea that memory is encoded by means of synaptic growth is not new. However, this idea has been difficult to demonstrate in the mammalian brain because of both the complexity of mammalian behavior and the neural circuitry by which it is supported. Here we examine how eyeblink classical conditioning affects synapse number within the cerebellum; the brain region essential for long-term retention of the conditioned response. Results showed eyeblink-conditioned rats to have significantly more synapses per neuron within the cerebellar interpositus nucleus than both explicitly unpaired and untrained controls. Further analysis showed that the increase was caused by the addition of excitatory rather than inhibitory synapses. Thus, development of the conditioned eyeblink response is associated with a strengthening of inputs from precerebellar nuclei rather than from cerebellar cortex. These results demonstrate that the modifications of specific neural pathways by means of synaptogenesis contributes to formation of a specific memory within the mammalian brain.
Partnerships in Rural Regeneration
Authors: Ward Neil
Published: October 2002

Westholm, E., Moseley, M. and Stenlås, N. (eds) 1999: LOCAL PARNERSHIPS AND RURAL DEVELOPMENT IN EUROPE: A LITERATURE REVIEW OF PRACTICE AND THEORY Cheltenham: Countryside and Community Research Unit, University of Gloucestershire, ISBN 91 88790 62 6, £17.99 paper, 245pp.

Esparcia, J., Moseley, M. and Noguera, J. (eds) 2000: EXPLORING RURAL DEVELOPMENT PARNERSHIPS IN EUROPE: AN ANALYSIS OF 330 LOCAL PARTNERSHIPS ACROSS EIGHT EU COUNTRIES Cheltenham: Countryside and Community Research Unit, University of Gloucestershire, ISBN 84 370 4445 6, £17.99 paper, 285pp.

Cacazzani, A. and Moseley, M. (eds) 2001: THE PRACTICE OF RURAL DEVELOPMENT PARNERSHIPS IN EUROPE: 24 CASE STUDIES IN SIX EUROPEAN COUNTRIES Cheltenham: Countryside and Community Research Unit, University of Gloucestershire, ISBN 88 498 0106 8, £17.99 paper, 398pp.

Moseley, M. and Cherrett, T. 2001: RURAL DEVELOPMENT PARNERSHIPS: GUIDELINES FOR GOOD PRACTICE IN THE UK Cheltenham: Countryside and Community Research Unit, University of Gloucestershire, no ISBN, £5.00 paperback pamphlet, 18pp.

Local Employment Policies

Campbell, M. and Meadows, P. 2001: WHAT WORKS LOCALLY? KEY LESSONS ON LOCAL EMPLOYMENT POLICIES, WORK AND OPPORTUNITY SERIES NO 24 York: Joseph Rowntree Foundation, ISBN 1 84263 004 0, £10.95 paper, 43 pages.

Local exchange trading systems

Meier, D. 2001: TAUSCHRINGE ALS BESONDERE BEWERTUNGSSYSTEME IN DER SCHATTENWIRTSCHAFT: EINE THEORETISCHE UND EMPIRISCHE ANALYSE. (LOCAL EXCHANGE TRADING SYSTEMS AS PARTICULAR SYSTEMS OF VALUATION IN THE SHADOW ECONOMY: A THEORETICAL AND EMPIRICAL ANALYSIS)

Berlin: Duncker & Humblot, ISBN 3 428 10210 X, 69 Euro paper, 273 pages.
Interferon γ Is Required for Activation-induced Death of T Lymphocytes
Authors: Refaeli Yosef , Van Parijs Luk , Alexander Stephen I. , Abbas Abul K.
Published: October 2002

The effector cytokine interferon γ (IFN-γ) may play a role in T cell homeostasis. We have examined the requirement for IFN-γ in one mechanism that regulates T cell expansion and survival, activation-induced cell death (AICD). CD4+ T cells lacking IFN-γ or the Stat1 transcription factor are resistant to AICD. IFN-γ is required for the production of caspases, and retrovirus-mediated expression of caspase-8 restores the sensitivity of Stat1-deficient T cells to AICD. In vitro, IFN-γ limits the expansion of T cells that are stimulated through their antigen receptors. Thus, IFN-γ may function to control the expansion and persistence of T cells by promoting caspase-8–dependent apoptosis.
Spatial variance of mobile aquatic organisms: capelin and cod in Newfoundland coastal waters
Authors: Horne John K. , Schneider David C.
Published: October 2002

Spatial variance in the distribution of aquatic mobile organisms differs from that of passive tracers such as phytoplankton or water temperature. On average, spatial variance of phytoplankton scales with sample unit as L2or equivalently with frequency asf−2. Limited evidence suggests that spatial variance in the distribution of mobile organisms is concentrated at relatively small scales, with little increase over larger scales: spatial variance scales asf−1or less. We investigated whether spatial variance in distributions of a mobile predator, Atlantic cod (Gadus morhua), and a schooling prey, capelin (Mallotus villosus), also scale with frequency asf−1. Acoustic surveys showed that at short time scales spatial variance in cod and capelin densities, as measured by spectral density, peaked at various scales ranging from 20 m to 10 km. At longer time scales, spatial variance of cod scaled asf−1.08at resolutions finer than 90 m, while scaling asf−0.18at coarser scales. Spatial variance of capelin scaled asf−1.1at resolutions finer than 400 m, while scaling asf−0.20at coarser scales. Spatial variance plots of krill and marine birds showed similar transitions from shallow to steep scaling. Shoaling, schooling and the aggregative response by predators to concentrations of prey were three processes hypothesized to influence spatial variance in distributions of mobile organisms. Numerical experiments showed that shoaling injects variance at large to intermediate scales, resulting in scalings flatter thanf−1. Additional experiments showed that schooling produces a transition from shallow to steep scaling as frequency increases. Spatial variance patterns in cod density were not due to aggregative responses by the predator to concentrations of capelin— there was no association, on average, at resolution scales from 20 m to 10 km. Exponent values for aquatic or terrestrial mobile organisms are predicted to be approximately two at the scale of an individual organism, 0.2 at scales that contain aggregations, and two at scales larger than that of populations. These findings suggest that relations between mobile organisms and large scale habitat variables will be difficult to detect, that stratified survey designs used to estimate commercial population sizes will be inefficient, and that rates of interaction between predator and prey will be underestimated if local observations are averaged over the spatial scale of the population.
Oxidative metabolism in muscle
Authors: Ferrari M. , Binzoni T. , Quaresima V.
Published: October 2002

Oxidative metabolism is the dominant source of energy for skeletal muscle. Near–infrared spectroscopy allows the non–invasive measurement of local oxygenation, blood flow and oxygen consumption. Although several muscle studies have been made using various near–infrared optical techniques, it is still difficult to interpret the local muscle metabolism properly. The main findings of near–infrared spectroscopy muscle studies in human physiology and clinical medicine are summarized. The advantages and problems of near–infrared spectroscopy measurements, in resting and exercising skeletal muscles studies, are discussed through some representative examples.
The influence of demographic factors on phase–modulated spectroscopy in adults
Authors: Levy Warren J.
Published: October 2002

The increased complexity of phase–modulated spectroscopy compared with incoherent light techniques of near–infrared spectroscopy is justified if measurement of path length is necessary. In order to assess the variability of optical transmission in the head of adults, 96 subjects of varying age, gender and skin pigmentation were studied using an experimental three–wavelength time–shared phase–modulated spectroscopy device. The optical path length was measured at each wavelength, and saturation and haemoglobin–free path length were calculated. The path length varied linearly with the separation of the optical probes, but gender, age or skin pigmentation were not associated with differences in path length. Haemoglobin saturation averaged 68 per cent and varied with age in a non–uniform fashion. Haemoglobin–free path length varied between genders, being 8 per cent longer in women than in men. Measurements could not be performed at 5 cm due to optical attenuation in 36 per cent of subjects These subjects were more often young, but they were not otherwise distinguished by gender or pigmentation differences. Subjects in whom measurements could be obtained at 5 cm had longer haemoglobin–free path lengths than did subjects in whom optical attenuation prevented these measurements. These data confirm the occurrence of significant differences in optical transmission in adults and support the use of phase–modulated spectroscopy techniques that measure path length.
Can repeated plasma donation by asymptomatic HIV–infected individuals delay the onset of AIDS?
Authors: Bainbridge D. R. , Lowdell M. W. , Hannet I. M. , Strauss K. W. , Karpas A.
Published: October 2002

Healthy HIV–positive regular donors of plasma in a programme of passive immunotherapy for AIDS patients were studied over a period of about two years. None developed symptoms of clinical progression; most seemed to make substantial gains of CD4 cells by comparison with asymptomatic individuals who were not donating. The effects of donation did not seem to diminish with repetition, and donor CD4 counts tended towards stabilizing within normal limits. Asymptomatic HIV–positive individuals were compared immunologically with ‘normals’ and people with AIDS, using a battery of 25 measurements on peripheral blood. The immunological profiles of donor and non–donor asymptomatics, indistinguishable at the start, became dissimilar: donors' profiles resembled AIDS less, non–donors became less like ‘normal’ and a few non–donor results could not be distinguished from AIDS. Improvement in the CD4 counts and amelioration of the immunological profile in donors provide prima facie evidence that plasmapheresis may be therapeutic for asymptomatic HIV–positive people. Further studies are justified.
Trees, soils, and food security
Authors: Sanchez Pedro A. , Buresh Roland J. , Leakey Roger R. B.
Published: October 2002

Trees have a different impact on soil properties than annual crops, because of their longer residence time, larger biomass accumulation, and longer–lasting, more extensive root systems. In natural forests nutrients are efficiently cycled with very small inputs and outputs from the system. In most agricultural systems the opposite happens. Agroforestry encompasses the continuum between these extremes, and emerging hard data is showing that successful agroforestry systems increase nutrient inputs, enhance internal flows, decrease nutrient losses and provide environmental benefits— when the competition for growth resources between the tree and the crop component is well managed. The three main determinants for overcoming rural poverty in Africa are (i) reversing soil fertility depletion, (ii) intensifying and diversifying land use with high–value products, and (iii) providing an enabling policy environment for the smallholder farming sector. Agroforestry practices can improve food production in a sustainable way through their contribution to soil fertility replenishment. The use of organic inputs as a source of biologically–fixed nitrogen, together with deep nitrate that is captured by trees, plays a major role in nitrogen replenishment. The combination of commercial phosphorus fertilizers with available organic resources may be the key to increasing and sustaining phosphorus capital. High–value trees— ‘Cinderella’ species, can fit in specific niches on farms, thereby making the system ecologically stable and more rewarding economically, in addition to diversifying and increasing rural incomes and improving food security. In the most heavily populated areas of East Africa, where farm size is extremely small, the number of trees on farms is increasing as farmers seek to reduce labour demands, compatible with the drift of some members of the family into the towns to earn off–farm income. Contrary to the concept that population pressure promotes deforestation, there is evidence that demonstrates that there are conditions under which increasing tree planting is occurring on farms in the tropics through successful agroforestry as human population density increases.
Perceptual categories for spatial layout
Authors: Kersten Daniel
Published: October 2002

The central problems of vision are often divided into object identification and localization. Object identification, at least at fine levels of discrimination, may require the application of top–down knowledge to resolve ambiguous image information. Utilizing top–down knowledge, however, may require the initial rapid access of abstract object categories based on low–level image cues. Does object localization require a different set of operating principles than object identification or is category determination also part of the perception of depth and spatial layout? Three–dimensional graphics movies of objects and their cast shadows are used to argue that identifying perceptual categories is important for determining the relative depths of objects. Processes that can identify the causal class (e.g. the kind of material) that generates the image data can provide information to determine the spatial relationships between surfaces. Changes in the blurriness of an edge may be characteristically associated with shadows caused by relative motion between two surfaces. The early identification of abstract events such as moving object/shadow pairs may also be important for depth from shadows. Knowledge of how correlated motion in the image relates to an object and its shadow may provide a reliable cue to access such event categories.
Cytokines and nitric oxide as effector molecules against parasitic infections
Authors: Liew Foo Y. , Wei Xiao–Qing , Proudfoot Lorna
Published: October 2002

Nitric oxide (NO) derived from L–arginine by the catalytic action of inducible NO synthase (iNOS) plays an important role in killing parasites. Many cell types express high levels of iNOS when activated by a number of immunological stimuli which include interferon–γ (IFN–γ), tumour necrosis factor alpha, and lipopolysaccharide. IFN–gamma is typically produced by the Th1 subset of CD4+ T cells, whose differentiation depends on interleukin–12 (IL–12) produced by macrophages. Mice with a disrupted iNOS gene were highly susceptible toLeishmania majorinfection compared with similarly infected control wild–type mice. The mutant mice developed significantly higher levels of TH1–cell response compared with the control mice, suggesting that NO is likely to be the effector molecule in the immunological control of this and other intracellular parasitic infections. To ensure their survival, theLeishmaniaparasites have evolved effective means to inhibit NO synthesis. The highly conserved major surface glycolipids, glycoinositol–phospholipids and lipophosphoglycan (LPG), ofLeishmaniaare potent inhibitors of NO synthesis. Furthermore, LPG can also inhibit IL–12 synthesis, thereby indirectly blocking the induction of iNOS. The evolutionary and therapeutic implications of these findings are discussed.
The importance of the back–signal from T cells into antigen–presenting cells in determining susceptibility to parasites
Authors: Müller Brigitte , Mitchison Avrion
Published: October 2002

It has long been known that certain MHC class II genes can dominantly suppress immune responses and so increase susceptibility to parasite infections, but the mechanism has been unclear. Recent work has revealed one way in which this form of suppression may operate through gating by MHC class II molecules of the back–signal from activated T cells into macrophages. The two known suppressive genes of the mouse are expressed in macrophages more extensively than are other class II genes. This is asscociated with suppresion of IL–4 production resulting, we infer, from overproduction in the macrophages of IL–12, the counter–cytokine to IL–4. The lack of IL–4 may itself be immunosuppressive, even for Th2 responses, and excess IL–12 can overinduce the antiproliferative cytokine IFN–gamma. Although this mechanism requires further substantiation, we believe that it offers a reasonable answer to an old conundrum.
Introduction to What are the parietal and hippocampal contributions to spatial cognition?, the proceedings of a Discussion held at The Royal Society
Authors: Burgess N. , Jeffery K. J. , Oapos;Keefe J.
Published: October 2002

Introduction to What are the parietal and hippocampal contributions to spatial cognition?, the proceedings of a Discussion held at The Royal Society on 19 and 20 March 1997. Organized by N. Burgess and J. O'Keefe and edited by N. Burgess, K. J. Jeffery and J. O'Keefe.
Modelling the interactions between ammonium and nitrate uptake in marine phytoplankton
Authors: Flynn Kevin J. , Fasham Michael J. R. , Hipkin Charles R.
Published: October 2002

An empirically based mathematical model is presented which can simulate the major features of the interactions between ammonium and nitrate transport and assimilation in phytoplankton. The model (ammonium-nitrate interaction model), which is configured to simulate a generic microalga rather than a specified species, is constructed on simplified biochemical bases. A major requirement for parametrization is that the N:C ratio of the algae must be known and that transport and internal pool sizes need to be expressed per unit of cell C. The model uses the size of an internal pool of an early organic product of N assimilation (glutamine) to regulate rapid responses in ammonium-nitrate interactions. The synthesis of enzymes for the reduction of nitrate through to ammonium is induced by the size of the internal nitrate pool and repressed by the size of the glutamine pool. The assimilation of intracellular ammonium (into glutamine) is considered to be a constitutive process subjected to regulation by the size of the glutamine pool. Longer term responses have been linked to the nutrient history of the cell using the N:C cell quota. N assimilation in darkness is made a function of the amount of surplus C present and thus only occurs at low values of N:C. The model can simulate both qualitative and quantitative temporal shifts in the ammonium-nitrate interaction, while inclusion of a derivation of the standard quota model enables a concurrent simulation of cell growth and changes in nutrient status.
Amnesia, memory and brain systems
Authors:   The American Association for Research into Nervous and Mental Diseases, Squire Larry R. , Zola Stuart M.
Published: October 2002

Bilateral damage to either the medial temporal lobe or the diencephalic midline causes an amnesic syndrome, i.e. a global impairment in the ability to acquire new memories regardless of sensory modality, and a loss of some memories, especially recent ones, from the period before amnesia began. The memory deficit can occur against a background of intact intellectual and perceptual functions. Two themes have been prominent in recent work. First, the amnesic syndrome is narrower than once believed in the sense that a number of learning and memory abilities are preserved (e.g. skill and habit learning, simple forms of conditioning and the phenomenon of priming). Second, the brain system damaged in amnesia has only a temporary role in memory. As time passes after learning, memory is reorganized and consolidated within neocortex, such that eventually medial temporal lobe and diencephalic structures are not needed for storage or retrieval.
Fiscal implications of population ageing
Authors: Johnson Paul
Published: October 2002

In all developed countries the fiscal ties of the tax and benefit system serve to complement, and sometimes substitute for, traditional family bonds between young and old. Older people are major recipients of public pensions and public health care systems. Since these public transfers and services are financed primarily from the taxes paid by people of working age, the welfare system in effect transfers resources from young to old. But rather than see the fiscal interdependency between young and old as being analogous to the ties that bind children, parents and grandparents together in familial networks, it is often interpreted as an oppressive burden that the old place on the young. This paper examines arguments that population ageing will exacerbate this burden, and may lead to the collapse of public welfare systems. It shows that the financial problems currently associated with public pensions are a function of system design rather than demographic change, and that wholesale privatization of pension systems will do little to solve the major dilemma: of persuading people to transfer a larger part of their lifetime income to their later years in order to sustain a reasonable standard of living throughout an ever lengthening period of retirement.
The Leeuwenhoek Lecture, 1997: Marek's disease herpesvirus: oncogenesis and prevention
Authors: Biggs P. M.
Published: October 2002

There are a number of neoplasias for which a herpesvirus is an essential part of the aetiology. Of these, Marek's disease is the most common and provides excellent opportunities for the study of a herpesvirus–induced tumour both experimentally and under natural conditions in the field. Marek's disease is caused by an alpha herpesvirus; it differs from the other oncogenic herpesviruses which are gamma herpesviruses. It is a ubiquitous virus in poultry populations of the world and is highly cell–associated and contagious, yet only a proportion of infected fowl develop tumours. Evidence is presented to suggest that at least one of the reasons for a wide variation in the incidence of the disease is a temporal interplay between virulent viruses and viruses of low or no virulence. The viral genes associated with the oncogenicity of Marek's disease virus (MDV) are discussed and it is concluded that it is likely that several genes are involved. Finally, a brief history of vaccination to control Marek's disease is given and mode of action discussed. It is concluded that the mechanism of protection is mainly through an antiviral cell mediated immune response, resulting in a lowered challenge virus burden. Marek's disease viruses over the past 40 years have been evolving greater oncogenicity, some of which are not adequately controlled by the vaccines that are currently available.

It is suggested that for MDV to produce tumours, there is a need for the cytolytic infection phase and that infection must be with an MDV which possesses a functional
gC
,
ICP4
for maintaining latency which allows the expression of at least the 1.8 kb family, pp38,
meq
, and possibly pp14 genes, for maintaining the tumour state and possibly initiating this state. Intervention in this process reduces the chance of tumour formation and incidence in a population which can occur through natural or man–mediated infection with non–pathogenic MDVs.
Conserved Disruptions in the Predicted Coiled-Coil Domains of Eukaryotic SMC Complexes: Implications for Structure and Function
Authors: Beasley Matthew , Xu Huiling , Warren William , McKay Michael
Published: October 2002

The structural maintenance of chromosome (SMC) proteins are required for a number of essential nuclear processes, including those of chromosome condensation, chromatid cohesion, and DNA repair. Eukaryotic SMC proteins form heterodimers capable of binding DNA and possess a DNA-stimulated ATPase activity. They have a characteristic structure of terminal globular domains with two internal arms that are predicted to form a coiled-coil structure interspaced with a globular “hinge” domain. We report here that the predicted coiled-coil arms are disrupted at conserved sites in SMC proteins. These disruptions, which vary in length and sequence identity, abolish the otherwise symmetrical secondary structure of antiparallel SMC heterodimers and provide the first evidence for a possible functional orientation of eukaryotic SMC complexes. The retention of these breaks between evolutionarily distant, yet related, SMC members indicates that they may have a fundamental role in SMC heterodimer function.