bluuebunny/crossref_metadata_2025 huggingface dataset:
Constitutive activity of Sauromatum guttatum alternative oxidase in Schizosaccharomyces pombe implicates residues in addition to conserved cysteines in α‐keto acid activation
Authors: Crichton Paul G. , Affourtit Charles , Albury Mary S. , Carré Jane E. , Moore Anthony L.
Published: December 2004

Activity of the plant mitochondrial alternative oxidase (AOX) can be regulated by organic acids, notably pyruvate. To date, only two well‐conserved cysteine residues have been implicated in this process. We report the functional expression of two AOX isozymes (Sauromatum guttatum Sg‐AOX and Arabidopsis thaliana At‐AOX1a) in Schizosaccharomyces pombe. Comparison of the response of these two isozymes to pyruvate in isolated yeast mitochondria and disrupted mitochondrial membranes reveals that in contrast to At‐AOX1a, Sg‐AOX activity is insensitive to pyruvate and appears to be in a constitutively active state. As both of these isozymes conserve the two cysteines, we propose that such contrasting behaviour must be a direct result of differences in their amino acid sequence and have subsequently identified novel candidate residues.
Sp1 site is crucial for the mouse claudin‐19 gene expression in the kidney cells
Authors: Luk John M. , Tong Man-Kit , Mok BoBo W. , Tam Po-Chor , Yeung William S.B. , Lee Kai-Fai
Published: December 2004

Members of the claudin family play important roles in the formation of tight junctions in the kidneys, liver and intestine. Claudin‐19 (Cldn19), a newly identified member of this family, is highly expressed in the kidney of the mouse. To have a better understanding on mouse claudin‐19 gene expression, a 0.9‐kb DNA fragment containing the 5′‐flanking region of the Cldn19 gene was isolated. DNA sequence comparison between the mouse and human Cldn19 promoter regions exhibited little homology. One transcription initiation site was located at 104 nucleotides upstream of the start codon (ATG) of the Cldn19 gene. The mouse claudin‐19 promoter lacked typical CAAT or GC‐box. Deletion constructs of the 0.9‐kb DNA fragment were generated and fused to a promoterless luciferase (Luc) reporter plasmid. Transfection studies using various kidney cell lines (MDCK, mIMCD3 and HEK293) revealed that the minimal promoter fragment resided in the −39 to −108 region, which contained a number of binding sites for transcription factors including Sp1. Site‐directed mutagenesis using specific oligo probes confirmed that Sp1 was crucial for Cldn19 transactivation in the three cell lines studied. Electromobility shift assay confirmed that the nuclear extracts of these cells bound to the Sp1 oligo derived from Cldn19 promoter, but not to the mutated Sp1 oligo probe. Moreover, this DNA–protein complex would be recognized by Sp1 antibody, indicating specific Sp1 binding. Collectively, our data suggest that Sp1 binds to the claudin‐19 promoter region and is responsible for its expression in the kidney cell lines in vitro.
Perturbation of the conformational equilibria in Ras by selective mutations as studied by 31P NMR spectroscopy
Authors: Spoerner Michael , Wittinghofer Alfred , Kalbitzer Hans Robert
Published: December 2004

Ras regulates a variety of different signal transduction pathways acting as molecular switch. It was shown by liquid and solid‐state 31P NMR spectroscopy that Ras exists in the guanosine‐5′‐(β,γ‐imido)triphosphate bound form in at least two conformational states interconverting in millisecond time scale. The relative population between the two conformational states affects drastically the affinity of Ras to its effectors. 31P NMR spectroscopy shows that the conformational equilibrium can be shifted specifically by point mutations, including mutations with oncogenic potential, thus modifying the effector interactions and their coupling to dynamic properties of the protein.
Leptin, from fat to inflammation: old questions and new insights
Authors: Otero Miguel , Lago Rocı́o , Lago Francisca , Casanueva Felipe F. , Dieguez Carlos , Gómez-Reino Juan Jesús , Gualillo Oreste
Published: December 2004

Leptin is 16 kDa adipokine that links nutritional status with neuroendocrine and immune functions. Initially thought to be a satiety factor that regulates body weight by inhibiting food intake and stimulating energy expenditure, leptin is a pleiotropic hormone whose multiple effects include regulation of endocrine function, reproduction, and immunity. Leptin can be considered as a pro‐inflammatory cytokine that belongs to the family of long‐chain helical cytokines and has structural similarity with interleukin‐6, prolactin, growth hormone, IL‐12, IL‐15, granulocyte colony‐stimulating factor and oncostatin M. Because of its dual nature as a hormone and cytokine, leptin links the neuroendocrine and the immune system. The role of leptin in the modulation of immune response and inflammation has recently become increasingly evident. The increase in leptin production that occurs during infection and inflammation strongly suggests that leptin is a part of the cytokine network which governs the inflammatory‐immune response and the host defense mechanisms. Leptin plays an important role in inflammatory processes involving T cells and has been reported to modulate T‐helper cells activity in the cellular immune response. Several studies have implicated leptin in the pathogenesis of autoimmune inflammatory conditions, such as experimental autoimmune encephalomyelitis, type 1 diabetes, rheumatoid arthritis, and intestinal inflammation. Very recently, a key role for leptin in osteoarthritis has been demonstrated: leptin indeed exhibits, in concert with other pro‐inflammatory cytokines, a detrimental effect on articular cartilage by promoting nitric oxide synthesis in chondrocytes. Here, we review the recent advances regarding leptin biology with a special focus on those actions relevant to the role of leptin in the pathophysiology of inflammatory processes and immune responses.
Heparin recovers AT1 receptor and its intracellular signal transduction in cultured vascular smooth muscle cells
Authors: Hashimoto Tatsuo , Kihara Minoru , Sato Keiko , Imai Nozomi , Tanaka Yutaka , Sakai Masashi , Tamura Kouichi , Hirawa Nobuhito , Toya Yoshiyuki , Kitamura Hitoshi , Umemura Satoshi
Published: December 2004

Although vascular smooth muscle cells (VSMCs) are widely used in cardiovascular research, their phenotypic change under various culture conditions is problematic to evaluate the experimental results obtained. The levels of angiotensin (Ang) type 1/2 (AT1/AT2) receptors as well as contractile and structural proteins are degraded through culture passages. The present study demonstrated that heparin recovered Ang receptors and differentiation markers, such as desmin, SM‐22 and smooth muscle α‐actin in VSMCs at the ninth passage. Heparin also potenciated Ang II‐induced activation for ERK1/2 and p38. These results suggest a potential value of heparin‐treated VSMCs as the model for analysis of Ang‐mediated signal transduction under physiological condition.
Mass spectrometry of intact ribosomes
Authors: Videler Hortense , Ilag Leopold L. , McKay Adam R.C. , Hanson Charlotte L. , Robinson Carol V.
Published: December 2004

The ability to maintain intact ribosomes in the mass spectrometer has enabled research into their changes in conformation and interactions. In the mass spectrometer, it is possible to induce dissociation of proteins from the intact ribosome and, in conjunction with atomic structures, to understand the factors governing their release. We have applied this knowledge to interpret the structural basis for release of proteins from ribosomes for which no high resolution structures are available, such as complexes with elongation factor G and ribosomes from yeast. We also describe how improvements in technology and understanding have widened the scope of our research and lead to dramatic improvements in quality and information available from spectra of intact ribosomes.
GABA shunt deficiencies and accumulation of reactive oxygen intermediates: insight from Arabidopsis mutants
Authors: Fait Aaron , Yellin Ayelet , Fromm Hillel
Published: December 2004

In plants, succinic semialdehyde dehydrogenase (SSADH)‐deficiency results in the accumulation of reactive oxygen intermediates (ROI), necrotic lesions, dwarfism, and hypersensitivity to environmental stresses [Bouché, N., Fait, A., Moller, S.G. and Fromm, H. (2003) Proc. Natl. Acad. Sci. USA. 100, 6843–6848]. We report that Arabidopsis ssadh knockout mutants contain five times the normal level of γ‐hydroxybutyrate (GHB), which in SSADH‐deficient mammals accounts for phenotypic abnormalities. Moreover, the level of GHB in Arabidopsis is light dependent. Treatment with γ‐vinyl‐γ‐aminobutyrate, a specific γ‐aminobutyrate (GABA)‐transaminase inhibitor, prevents the accumulation of ROI and GHB in ssadh mutants, inhibits cell death, and improves growth. These results provide novel evidence for the relationship between the GABA shunt and ROI, which may, in part, explain the phenotype of SSADH‐deficient plants and animals.
Bonamia exitiosa epizootic in Ostrea chilensis from Foveaux Strait, southern New Zealand between 1986 and 1992
Authors: Cranfield H.J. , Dunn A. , Doonan I.J. , Michael K.P.
Published: December 2004

Disease caused by the haplosporidian parasite, Bonamia exitiosa, swept through the dredge oyster (Ostrea chilensis) population of Foveaux Strait between 1986 and 1992, with consequent mortality reducing the population to 9% of the pre-disease level. Dead and dying oysters were first seen by fishers in far western Foveaux Strait in 1985 and more were found further east in 1986. Infection spread slowly through Foveaux Strait so the progress of the epizootic can be described from population surveys. A wave of infection radiated through the oyster population from the epicentre of infection in central western Foveaux Strait, and was followed by a wave of mortality. The epizootic ceased in oyster beds around the margins of oyster distribution in 1992. Infective particles released by diseased oysters spread through the water to infect other oysters directly. The epizootic broadly fitted a simple deterministic epizootic model and suggested that both diffusion and turbulent processes were important in transmission of infection. Bonamia exitiosa was also present in oysters at the end of an epizootic in 1964 and was probably the cause of that epizootic. Bonamiasis appears to be an endemic disease in Foveaux Strait. The high mortality in the 1986–1992 epizootic was like that caused by a newly introduced disease in an immunologically naïve population. We propose that other stressors have increased the susceptibility of oysters to this disease. Mechanical disturbance of oysters by increasingly intense dredging appears to be a major source of stress, as does the increasing scale of modification of benthic habitat by fishing. Recovery of the oyster population after the epizootic is closely linked to regeneration of habitat. The prognosis for the fishery could be improved by mitigating mechanical disturbance during dredging by use of lighter dredges and less damaging towing strategies, as well as pursuing rotational fishing strategies that allow benthic habitat to regenerate in undisturbed areas.
Digestion of capelin, Mallotus villosus (Müller), herring, Clupea harengus L., and polar cod, Boreogadus saida (Lepechin), otoliths in a simulated seal stomach
Authors: Christiansen Jørgen S. , Gamst Moen Anne-Grethe , Hansen Thomas H. , Nilssen Kjell T.
Published: December 2004

The ability of otoliths to withstand digestion in a seal stomach appears to differ between fish taxa with the otoliths of gadoids being particularly resistant to gastric erosion. Few studies have examined the effect of otolith size on the rate of otolith dissolution. We exposed 50 otoliths (total sagittal length: 1.4–7.0 mm) from capelin (Mallotus villosus, n = 20), herring (Clupea harengus, n = 10), and polar cod (Boreogadus saida, n = 20) as well as nine whole capelin (total body length = 100–120 mm) to digestive solutions assumed to mimic the gastric environment of Arctic seals in vitro (pH: ∼2, temperature: ∼37°C, pepsin concentrations: 0–750-μg ml−1 solution). Pepsin did not affect the dissolution rates of sagittae but resulted in a complete digestion of whole capelin within 10 h. Irrespective of species examined, sagittae fitted the same pattern of dissolution rate with the smaller sagittae being dissolved faster than did the larger ones. We suggest that scaling controls sagittal dissolution rates (DR, μm min−1), and that the sagittae from the three forage fish combined dissolve according to sagittal length (SL, mm) as shown by the equation: DRCommon = 27.348e−0.120 SL (n = 46, r2 = 0.688, p < 0.001). Given this relationship, the numerical importance of prey taxa with the smaller otoliths – i.e. also the small-sized gadoids (polar cod) – is likely to be underestimated in feeding studies with Arctic seals.
An assessment of the upstream migration and reproductive behaviour of allis shad (Alosa alosa L.) using acoustic tracking
Authors: Acolas M.L. , Bégout Anras M.L. , Véron V. , Jourdan H. , Sabatié M.R. , Baglinière J.L.
Published: December 2004

We provide a detailed description of the migratory and reproductive behaviour of allis shad (Alosa alosa L.), a species that is in decline in Europe. Adult swimming behaviour during the last part of upstream migration and on a spawning ground downstream of an insurmountable dam was studied in detail and its main features identified, “characterized” in this context. Mobile telemetry and a fixed telemetry system were used to record fish positions and to monitor 23 acoustically tagged individuals (17 females and six males) during the 2001 and 2002 reproductive seasons. Allis shad showed considerable exploratory behaviour, and a rest area was observed 1.5 km downstream of the spawning ground. Thirteen individuals were observed on the spawning area, though both males and females spent most of their time (70–99%) away from it. Male and female residency times on the spawning area were, respectively, 1–11 days and 1–7 days, and females were observed during both day and night on the spawning ground. In 2002, an analysis of the 3D swimming behaviour on the spawning ground of six individuals allowed us to estimate the number of spawning events per fish. Males participated in more spawning acts (up to 60) than females (0–2).
Application of pre-fishery abundance modelling and Bayesian hierarchical stock and recruitment analysis to the provision of precautionary catch advice for Irish salmon (Salmo salar L.) fisheries
Authors: Ó Maoiléidigh N. , McGinnity P. , Prévost E. , Potter E.C.E , Gargan P. , Crozier W.W. , Mills P. , Roche W.
Published: December 2004

Ireland has one of the last remaining commercial salmon driftnet fisheries in the North Atlantic, with recent catches averaging 162 000 salmon (1997–2003), approximately 20% of the total landings of salmon in the entire North Atlantic. Since 2001, the Irish commercial salmon fishery has been managed on the basis of Total Allowable Catch (TAC) in each of 17 salmon fishing districts. This has been made possible by applying a number of new and innovative techniques to the estimation of conservation limits (CLs) and pre-fishery abundance (PFA) for combined stocks in each district. Stock and recruitment parameters from well-monitored European rivers were “transported” to all Irish rivers using a Bayesian hierarchical stock and recruitment (BHSRA) model. This provided the posterior probability distributions of the model parameters and related reference points, including individual river CLs. District PFA and the number of spawners were estimated for a baseline period of 1997–2003, using district catch data, estimates of unreported catch, and exploitation rate. Harvest guidelines were established on the basis of surplus of spawning fish over the CL for the baseline period. In line with scientific advice, the commercial fishery has been reduced from 212 000 fish in 2002 to 182 000 in 2003. In 2004, a total catch (including the rod catch) of approximately 160 000 wild salmon was advised.
Considerations for using spawner reference levels for managing single- and mixed-stock fisheries of Atlantic salmon
Authors: Chaput Gerald
Published: December 2004

The probability of achieving the spawning requirement objective of Atlantic salmon (Salmo salar L.) is defined by the stochastic properties of small numbers and biological characteristics of the stock. The uncertainty in achieving the spawning escapement objective is greater for small stocks than for large ones, such that measures of annual performance are more variable for small stocks. Summing individual river spawner requirements into a regional requirement reduces the probability of meeting the objectives simultaneously in all rivers. Variations in productivity among stocks, when not accounted for, can result in under-escapement in areas of lower productivity. The impact of mixed-stock fisheries can be most important for small stocks, and especially if these are of low relative productivity. Increasing the regional spawner requirement in an attempt to compensate for lower productivity may alleviate the problem somewhat, but it is not a guaranteed solution to the challenge of protecting all stocks, specifically those of low productivity in mixed-stock fishery situations. Each mixed-stock fishery situation can be evaluated on a case-by-case basis using Monte Carlo techniques.
The Anatomical Basis for Reverse First to Fifth Dorsal Metacarpal Arterial Flaps
Authors: OMOKAWA S. , TANAKA Y. , RYU J. , KISH VINCENT L
Published: December 2004

This study discusses the anatomical basis for reverse first to fifth dorsal metacarpal arterial flaps. The arterial pattern and size of the first to fifth dorsal metacarpal arteries were examined in 20 fresh cadaver hands. Their connections to the palmar arterial system at the metacarpal head were observed, and the location, number and diameter of skin perforators from each dorsal metacarpal artery were measured. The first to fourth dorsal metacarpal arteries were found in all specimens; the fifth dorsal metacarpal artery was found in 19 of our 20 specimens. The mean diameters of the first to fifth arteries at their bifurcation site were 0.6, 0.8, 0.5, 0.4 and 0.2 mm, respectively. Each artery gave off four to eight skin perforators (diameter: 0.1–0.3 mm) between the metacarpal head and base. The first to third dorsal metacarpal arteries consistently connected to the palmar arterial system, and connections between the fourth and fifth dorsal metacarpal arteries and the palmar system were found in 65% and 40% of specimens.
The changes in the migration patterns in the post-Soviet states: the first decade
Authors: Korobkov Andrei V. , Zaionchkovskaia Zhanna A.
Published: December 2004

Following a short-term burst of migration activity after the dissolution of the USSR, the current situation is marked by the unusually low population territorial mobility, defined by both the political and, increasingly, the socioeconomic factors. While this trend indicates some degree of minority accommodation, it also demonstrates the depth of economic crisis and increasing socioeconomic differentiation. Visible also is the disproportionate influence exercised by Russia on the formation of migration flows in the region. Remaining the major recipient of migrants, Russia increasingly plays a role of supplier of labor migrants to the West, and acts as a ‘‘bridge’’ for those attempting to reach Western Europe. Meanwhile, Russia still lacks an effective legislative base, institutional mechanisms, and political will for dealing with the new migration flows.
Three‐dimensional flushing times of the Persian Gulf
Authors: Sadrinasab Masoud , Kämpf Jochen
Published: December 2004

A three‐dimensional hydrodynamic model is employed in a fully prognostic mode to derive flushing times of the Persian Gulf—an evaporation‐driven inverse estuary that is governed by import of surface water from the adjacent ocean and export of saline bottom gulf water through the Strait of Hormuz. During spring and summer, a cyclonic overturning circulation establishes along the full length of the Gulf. During autumn and winter, this circulation breaks up into mesoscale eddies, laterally stirring most of the Gulf's surface waters. As a result of this, 95% flushing times of surface waters are shortest (1–3 yr, increasing with distance from the Strait) along the Iranian coast, but are much longer (>5 yr) along the coasts of Kuwait and Saudi Arabia. Owing to density stratification introduced by the surface inflow of ocean water, flushing times of bottom waters are ∼6 yr in most parts of the Gulf.
Ocean subsurface warming as a mechanism for coupling Dansgaard‐Oeschger climate cycles and ice‐rafting events
Authors: Shaffer Gary , Olsen Steffen Malskær , Bjerrum Christian J.
Published: December 2004

Heinrich events have been attributed to surging of the Laurentide ice sheet every 7 thousand years or so during glacial time. These massive ice‐rafting events only occurred during cold phases of millennial‐scale, Dansgaard‐Oeschger climate cycles. Other observed ice‐rafting events, sourced from ice streams at various locations around the northern North Atlantic, occurred during all Dansgaard‐Oeschger cold phases and led Heinrich events when the latter took place. Here it is suggested that ocean subsurface warming in the northern North Atlantic during the cold phases may provide the key to explaining these climate ‐ ice rafting phasings. Such warming would lead to ice shelf melting and breakup. Without buttressing by ice shelves, ice streams may surge, leading to increased iceberg production. This interpretation is supported by results of a simplified, coupled climate model and by available sediment and ice sheet data.
Acceleration of relativistic electrons due to resonant scattering by whistler mode waves generated by temperature anisotropy in the inner magnetosphere
Authors: Katoh Yuto , Omura Yoshiharu
Published: December 2004

Resonant interaction between relativistic electrons and monochromatic whistler mode wave is studied with a self‐consistent simulation model. We treat a monochromatic whistler mode wave excited by an instability associated with a temperature anisotropy of medium‐energy electrons. In the simulation result the monochromatic whistler mode wave traps relativistic electrons which satisfy the resonance condition. Especially, in a case in which oppositely propagating monochromatic waves coexist, we find that a combined effect of wave trapping connects diffusion curves and opens a route for the rapid acceleration. The motion of the trapped relativistic electrons in the momentum space is estimated from the intersection of resonance curves and the scale of trapping region which is determined by both the trapping velocity and the resonance velocity. The present simulation reveals that selected resonant electrons are effectively accelerated in a homogeneous system where both forward and backward traveling waves interact with the relativistic electrons.
Fluctuations in biosiliceous production and the generation of Early Cretaceous oceanic anoxic events in the Pacific Ocean (Shatsky Rise, Ocean Drilling Program Leg 198)
Authors: Robinson Stuart A. , Williams Trevor , Bown Paul R.
Published: December 2004

Integration of geophysical logs with sedimentological, biostratigraphic, and physical properties data from poorly recovered chert‐rich sequences at Ocean Drilling Program Leg 198 Sites 1207 and 1213 allows us to propose an Aptian–Albian (Early Cretaceous) depositional history for Shatsky Rise (North Pacific Ocean). The logs indicate that the lower Aptian and lower Albian deposits are relatively lithified and unporous compared to contiguous sediments. These characteristics are best explained by increased siliceous cementation that resulted from an elevated flux of radiolarians to the seafloor. The intervals of increased biosiliceous production may record a biotic response to enhanced nutrient delivery, coeval with (but longer in duration than) oceanic anoxic events (OAEs) 1a (early Aptian) and 1b (early Albian). On Shatsky Rise, OAE 1a is represented by organic‐carbon‐rich sediments, but OAE 1b is not. Thus “black shale” deposition in the Pacific Ocean was only possible when a “carbon‐burial threshold” was crossed. We speculate that this threshold was related to the balance between productivity and carbon oxidation and that, ultimately, the supply of biolimiting nutrients through hydrothermal alteration of basalt may have been the key to the development of “black shale” in the Pacific basin.
Experimental apparatus and sample preparation techniques for directional solidification
Authors: Utter B. , Ragnarsson R. , Bodenschatz E.
Published: December 2004

We describe a directional solidification stage which allows the controlled solidification of transparent organic alloys. We present two variations of the experiment. In one, large aspect ratio sample cells can be rotated with respect to the temperature gradient between runs, allowing full 360° control over in-plane sample orientation. In the other, thin-walled capillaries are pulled through an oil-filled channel which is optimized for high speed solidification studies (V≈5mm∕s). The use of large aspect ratio cells (≈11cm diameter rotatable) and long capillary cells (≈38cm) allows solidification for significant times even at rapid solidification rates. We describe in detail material purification, cell construction, and vacuum filling procedures which allow high quality sample preparation completely under inert atmosphere. Succinonitrile is purified using a sublimation apparatus and samples are filled directly from the sublimation chamber. Vacuum-filling epoxied cells produces long-lasting degassed samples. The techniques presented are also suitable for similar materials such as liquid crystals, CBr4, and pivalic acid. Additional features of the experiment include a linear stepper motor and linear temperature gradient (3–150K∕cm).
High sensitivity gas permeability measurement system for thin plastic films
Authors: Ranade A. , D’Souza N. A. , Wallace R. M. , Gnade B. E.
Published: December 2004

We have developed a system to quantitatively measure the permeation of gases through thin flexible substrates with high sensitivity. The system consists of two chambers, a high pressure side and an ultrahigh vacuum (UHV) side, separated by the flexible sample to be analyzed. The system is calibrated using a combination of a National Institute of Standards and Technology traceable calibrated He leak and a variable aperture calibrated orifice. The base total pressure for the UHV side is 1–3×10−10Torr. The partial pressure of individual gases that we are studying is <10−10Torr. The sample to be measured is secured between the two chambers using two 2.75 conflat flanges, two copper gaskets, and two indium “O” rings. The key factors that impact sensitivity and quantification are (1) reducing the residual partial pressure of the gas of interest to as low a value as possible on the UHV side of the system, (2) sealing the plastic sample between the two chambers with no detectable gas leakage around the sample or from the outside, (3) supporting the plastic substrate so that it can withstand 700Torr pressure on the high pressure side, and (4) developing a calibration procedure that closely mimics the actual permeability measurement. The system allows us to measure permeation rates as low as 1×10−6g∕m2-day for He, 1×10−6g∕m2-day for O2, and 5×10−7g∕m2-day for Ar.
Current layer cascade in collisionless electron-magnetohydrodynamic reconnection and electron compressibility effects
Authors: Del Sarto D. , Califano F. , Pegoraro F.
Published: December 2004

The nonlinear phase of a magnetic field line reconnection instability in a collisionless two-dimensional cold plasma is investigated in the Hall dominated regime, described by the electron-magnetohydrodynamic equations, which corresponds to the frequency range of whistler waves. It is found that the regular pattern of current density layers that forms in the initial nonlinear phase of the reconnection instability is destroyed by the onset of a Kelvin–Helmholtz-type instability and the formation of current jets that develop into vortex rings. These processes can be interpreted in terms of a Hasegawa–Mima-type regime inside the magnetic island and lead to the creation of magnetic vortices. It is shown that electron compressibility, which is related to charge separation, tends to stabilize these processes.
Stimulation of proteoglycan synthesis by glucuronosyltransferase-I gene delivery: A strategy to promote cartilage repair
Authors: Venkatesan N. , Barré L. , Benani A. , Netter P. , Magdalou J. , Fournel-Gigleux S. , Ouzzine M.
Published: December 2004

Osteoarthritis is a degenerative joint disease characterized by a progressive loss of articular cartilage components, mainly proteoglycans (PGs), leading to destruction of the tissue. We investigate a therapeutic strategy based on stimulation of PG synthesis by gene transfer of the glycosaminoglycan (GAG)-synthesizing enzyme, β1,3-glucuronosyltransferase-I (GlcAT-I) to promote cartilage repair. We previously reported that IL-1β down-regulated the expression and activity of GlcAT-I in primary rat chondrocytes. Here, by using antisense oligonucleotides, we demonstrate that GlcAT-I inhibition impaired PG synthesis and deposition in articular cartilage explants, emphasizing the crucial role of this enzyme in PG anabolism. Thus, primary chondrocytes and cartilage explants were engineered by lipid-mediated gene delivery to efficiently overexpress a human GlcAT-I cDNA. Interestingly, GlcAT-I overexpression significantly enhanced GAG synthesis and deposition as evidenced by
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S-sulfate incorporation, histology, estimation of GAG content, and fluorophore-assisted carbohydrate electrophoresis analysis. Metabolic labeling and Western blot analyses further suggested that GlcAT-I expression led to an increase in the abundance rather than in the length of GAG chains. Importantly, GlcAT-I delivery was able to overcome IL-1β-induced PG depletion and maintain the anabolic activity of chondrocytes. Moreover, GlcAT-I also restored PG synthesis to a normal level in cartilage explants previously depleted from endogenous PGs by IL-1β-treatment. In concert, our investigations strongly indicated that GlcAT-I was able to control and reverse articular cartilage defects in terms of PG anabolism and GAG content associated with IL-1β. This study provides a basis for a gene therapy approach to promote cartilage repair in degenerative joint diseases.
Ecosystem consequences of bird declines
Authors: Şekercioğlu Çağan H. , Daily Gretchen C. , Ehrlich Paul R.
Published: December 2004

We present a general framework for characterizing the ecological and societal consequences of biodiversity loss and applying it to the global avifauna. To investigate the potential ecological consequences of avian declines, we developed comprehensive databases of the status and functional roles of birds and a stochastic model for forecasting change. Overall, 21% of bird species are currently extinction-prone and 6.5% are functionally extinct, contributing negligibly to ecosystem processes. We show that a quarter or more of frugivorous and omnivorous species and one-third or more of herbivorous, piscivorous, and scavenger species are extinction-prone. Furthermore, our projections indicate that by 2100, 6–14% of all bird species will be extinct, and 7–25% (28–56% on oceanic islands) will be functionally extinct. Important ecosystem processes, particularly decomposition, pollination, and seed dispersal, will likely decline as a result.
The coevolution of ritual and society: New
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C dates from ancient Mexico
Authors: Marcus Joyce , Flannery Kent V.
Published: December 2004

New
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C dates from Oaxaca, Mexico, document changes in religious ritual that accompanied the evolution of society from hunting and gathering to the archaic state. Before 4000 B.P. in conventional radiocarbon years, a nomadic egalitarian lifeway selected for unscheduled (ad hoc) ritual from which no one was excluded. With the establishment of permanent villages (4000–3000 B.P.), certain rituals were scheduled by solar or astral events and restricted to initiates/social achievers. After state formation (2050 B.P.), many important rituals were performed only by trained full-time priests using religious calendars and occupying temples built by corvée labor. Only 1,300–1,400 years seem to have elapsed between the oldest known ritual building and the first standardized state temple.
Effects of Long‐Term Episodic Access to Ethanol on the Expression of an Alcohol Deprivation Effect in Low Alcohol–Consuming Rats
Authors: Bell Richard L. , Rodd Zachary A. , Boutwell Caron L. , Hsu Cathleen C. , Lumeng Lawrence , Murphy James M. , Li Ting‐Kai , McBride William J.
Published: December 2004

Background: The alcohol‐preferring (P) and ‐nonpreferring (NP) and high alcohol–drinking (HAD) and low alcohol–drinking (LAD) rats have been selectively bred for divergent preference for ethanol over water. In addition, both P and HAD rats display an alcohol deprivation effect (ADE). This study was undertaken to test whether the NP, LAD‐1, and LAD‐2 lines of rats could display an ADE as well.

Method: Adult female NP, LAD‐1, and LAD‐2 rats were given concurrent access to multiple concentrations of ethanol [5, 10, 15% (v/v)] and water in an ADE paradigm involving an initial 6 weeks of 24‐hr access to ethanol, followed by four cycles of 2 weeks of deprivation from and 2 weeks of re‐exposure to ethanol (5, 10, and 15%). A control group had continuous access to the ethanol concentrations (5, 10, and 15%) and water through the end of the fourth re‐exposure period.

Results: For NP rats, a preference for the highest ethanol concentration (15%) was evident by the end of the fifth week of access (∼60% of total ethanol fluid intake). Contrarily, LAD rats did not display a marked preference for any one concentration of ethanol. All three lines displayed an ADE after repeated cycles of re‐exposure to ethanol, with the general ranking of intake being LAD‐1 > NP > LAD‐2 (e.g., for the first day of reinstatement of the third re‐exposure cycle, intakes were 6.5, 2.9, and 2.4 g/kg/day compared with baseline values of 3.1, 2.0, and 1.3 g/kg/day for each line, respectively). By the 13th week, rats from all three lines, with a ranking of LAD‐1 > NP > LAD‐2, were drinking more ethanol (3.3, 2.2, and 2.0 g/kg/day, respectively) compared with their consumption during the first week of access (∼1.1 g/kg/day for all three lines).

Conclusion: These data indicate that access to multiple concentrations of ethanol and exposure to multiple deprivation cycles can partially overcome a genetic predisposition of NP, LAD‐1, and LAD‐2 rats for low alcohol consumption. In addition, the findings suggest that genetic control of low alcohol consumption in rats is not associated with the inability to display an ADE.
Drinking and Spouse Abuse Among U.S. Army Soldiers
Authors: Bell Nicole S. , Harford Thomas , McCarroll James E. , Senier Laura
Published: December 2004

Background: This study examines the relationship between typical weekly drinking and perpetration of spouse abuse as well as the relationship between the perpetrator's typical weekly drinking and alcohol use during the abuse event among U.S. Army male soldiers.

Methods: Cases include all active duty, male, enlisted Army spouse abusers identified in the Army's Central Registry who had also completed an Army Health Risk Appraisal Survey (HRA) between 1991 and 1998 (N= 9534). Cases were matched on sex, rank, and marital status with 21,786 control subjects who had also completed an HRA.

Results: In multivariate logistic regression models, heavy drinkers (22 or more drinks per week) were 66% more likely to be spouse abusers than were abstainers (odds ratio 1.66; 95% confidence interval 1.40–1.96). In addition, self‐reported moderate and heavy drinkers were three times as likely and light drinkers (1–7 drinks per week) were twice as likely as nondrinkers to be drinking during the time of the abuse event.

Conclusion: Self‐reported heavy drinking is an independent risk factor for perpetration of spouse abuse among male, enlisted Army soldiers. Even 5 years or more after ascertainment of typical drinking habits, there is a significant association between self‐reported heavy drinking and alcohol involvement at the time of the spouse abuse event. Personnel who work with perpetrators and victims of spouse abuse should be trained carefully to query about current and typical drinking patterns.
Ethanol's Effects on Gait Dynamics in Mice Investigated by Ventral Plane Videography
Authors: Kale Ajit , Amende Ivo , Meyer Gerd P. , Crabbe John C. , Hampton Thomas G.
Published: December 2004

Background: Performance of mice in motor function tests for ethanol sensitivity is often task dependent, not reflective of coordinated movement, and reported qualitatively. Therefore, we applied a new imaging technique to record and quantify coordinated gait dynamics in mice in response to ethanol.

Methods: We applied ventral plane videography to record and report gait indices in mice walking on a transparent treadmill belt. We examined the effects of ethanol on gait in C57BL/6J (B6) and DBA/2J (D2) mice walking at a speed of 25 cm/sec. B6 and D2 are two inbred strains that are widely used to study the genetic influences of ethanol on motor function.

Results: Gait posture in D2 mice was less stable than in B6 mice. B6 mice always showed an alternate step sequence, whereas D2 mice sometimes showed cruciate and rotary step sequences. Ethanol in increasing doses increased stride frequency, decreased stride length, and increased stride length variability in D2 mice but not in B6 mice. The forelimb braking duration was significantly shortened and the hind limb propulsion duration was significantly prolonged with a high dose of ethanol in D2 mice but not in B6 mice. Differences in gait indices between the two strains of mice were more pronounced of the forelimbs with the highest dose of ethanol (2.75 g/kg).

Conclusion: Our data suggest that the higher susceptibility of D2 compared with B6 mice to the effects of ethanol on motor function may be attributed to less stable basal gait characteristics that are perturbed by ethanol. The ability of this method to quantify step sequence patterns and gait indices of forelimb and hind limbs could provide new data regarding ethanol‐induced motor incoordination.
A Polymorphism of the μ‐Opioid Receptor Gene (OPRM1) and Sensitivity to the Effects of Alcohol in Humans
Authors: Ray Lara A. , Hutchison Kent E.
Published: December 2004

Background: Recent research has implicated the endogenous opioid system in the development of alcohol use disorders. The A118G polymorphism of the OPRM1 gene has been shown to confer functional differences to μ‐opioid receptors, such that the G variant binds β‐endorphin three times more strongly than the A variant. The goal of this study was to test whether the A118G polymorphism is associated with sensitivity to the effects of alcohol.

Methods: Participants who were either homozygous for the A allele (n= 23) or heterozygous (n= 15) received intravenous doses of alcohol designed to reach three target levels of breath alcohol concentration: 0.02, 0.04, and 0.06. The testing procedure consisted of measures of subjective intoxication, stimulation, sedation, and mood states at baseline and at each of the three target breath alcohol concentrations.

Results: The results suggested that individuals with the G allele reported higher subjective feelings of intoxication, stimulation, sedation, and happiness across trials as compared with participants with the A allele. Furthermore, participants with the G allele were almost three times more likely to report a positive family history of alcohol use disorders than participants with the A allele.

Conclusions: These findings may help to explain previous research suggesting that naltrexone is more effective among individuals with the G allele. A medication that reduces feelings of euphoria after alcohol consumption may be more successful among individuals with a genetic predisposition to greater feelings of euphoria after consuming alcohol.
Genome sequence of the non-pathogenic strain 15 of pneumonia virus of mice and comparison with the genome of the pathogenic strain J3666
Authors: Thorpe L. C. , Easton A. J.
Published: December 2004

Pneumonia virus of mice (PVM) is a member of the subfamily Pneumovirinae and is the closest known relative of respiratory syncytial virus. Both viruses cause pneumonia in their respective hosts. Here, the genome sequences of two strains of PVM, non-pathogenic strain 15 and pathogenic strain J3666, are reported. Comparison of the genome sequences revealed 59 nucleotide differences between the two strains, 37 of which were coding. The nucleotide differences were spread throughout the genome, affecting cis-acting regulatory regions and seven of the ten genes. Development of a reverse-genetics system for PVM should allow further elucidation of the functional importance of the genetic differences between the two strains identified here.
Specificity of serum neutralizing antibodies induced by transient immune suppression of inapparent carrier ponies infected with a neutralization-resistant equine infectious anemia virus envelope strain
Authors: Howe Laryssa , Craigo Jodi K. , Issel Charles J. , Montelaro Ronald C.
Published: December 2004

It has been previously reported that transient corticosteroid immune suppression of ponies experimentally infected with a highly neutralization resistant envelope variant of equine infectious anemia virus (EIAV), designated EIAVΔPND, resulted in the appearance of type-specific serum antibodies to the infecting EIAVΔPNDvirus. The current study was designed to determine if this induction of serum neutralizing antibodies was associated with changes in the specificity of envelope determinants targeted by serum antibodies or caused by changes in the nature of the antibodies targeted to previously defined surface envelope gp90 V3 and V4 neutralization determinants. To address this question, the envelope determinants of neutralization by post-immune suppression serum were mapped. The results demonstrated that the neutralization sensitivity to post-immune suppression serum antibodies mapped specifically to the surface envelope gp90 V3 and V4 domains, individually or in combination. Thus, these data indicate that the development of serum neutralizing antibodies to the resistant EIAVΔPNDwas due to an enhancement of host antibody responses caused by transient immune suppression and the associated increase in virus replication.
Influenza A mutant viruses with altered NS1 protein function provoke caspase-1 activation in primary human macrophages, resulting in fast apoptosis and release of high levels of interleukins 1β and 18
Authors: Stasakova Jana , Ferko Boris , Kittel Christian , Sereinig Sabine , Romanova Julia , Katinger Hermann , Egorov Andrej
Published: December 2004

Several NS1 mutant viruses of human influenza A/PR/8/34 (H1N1) virus were tested for their ability to induce pro-inflammatory cytokines in primary human macrophages. The findings revealed a pronounced difference in the virus-induced cytokine pattern, depending on the functionality of the NS1 protein-encoded domains. The PR8/NS1–125 mutant virus, which encodes the first 125 aa of the NS1 protein, thus lacking the C-terminal domains, induced significantly higher amounts of beta interferon, interleukin (IL) 6, tumour necrosis factor alpha and CCL3 (MIP-1α) when compared with the A/PR/8/34 wild-type virus. However, this mutant virus was as efficient as wild-type virus in the inhibition of IL1βand IL18 release from infected macrophages. Another group of viral mutants either lacking or possessing non-functional RNA-binding and dimerization domains induced 10–50 times more biologically active IL1βand five times more biologically active IL18 than the wild-type or PR8/NS1–125 viruses. The hallmark of infection with this group of mutant viruses was the induction of rapid apoptosis in infected macrophages, which correlated with the enhanced activity of caspase-1. These results indicated that the NS1 protein, through the function of its N-terminal domains, might control caspase-1 activation, thus repressing the maturation of pro-IL1β-, pro-IL18- and caspase-1-dependent apoptosis in infected primary human macrophages.
Characterization of an infectious cDNA copy of the genome of a naturally occurring, avirulent coxsackievirus B3 clinical isolate
Authors: Lee C.-K. , Kono K. , Haas E. , Kim K.-S. , Drescher K. M. , Chapman N. M. , Tracy S.
Published: December 2004

Group B coxsackieviruses (CVB) cause numerous diseases, including myocarditis, pancreatitis, aseptic meningitis and possibly type 1 diabetes. To date, infectious cDNA copies of CVB type 3 (CVB3) genomes have all been derived from pathogenic virus strains. An infectious cDNA copy of the well-characterized, non-pathogenic CVB3 strain GA genome was cloned in order to facilitate mapping of the CVB genes that influence expression of a virulence phenotype. Comparison of the sequence of the parental CVB3/GA population, derived by direct RT-PCR-mediated sequence analysis, to that of the infectious CVB3/GA progeny genome demonstrated that an authentic copy was cloned; numerous differences were observed in coding and non-coding sequences relative to other CVB3 strains. Progeny CVB3/GA replicated similarly to the parental strain in three different cell cultures and was avirulent when inoculated into mice, causing neither pancreatitis nor myocarditis. Inoculation of mice with CVB3/GA protected mice completely against myocarditis and pancreatitis induced by cardiovirulent CVB3 challenge. The secondary structure predicted for the CVB3/GA domain II, a region within the 5′ non-translated region that is implicated as a key site affecting the expression of a cardiovirulent phenotype, differs from those predicted for cardiovirulent and pancreovirulent CVB3 strains. This is the first report characterizing a cloned CVB3 genome from an avirulent strain.
Recovery of APOBEC3-edited human immunodeficiency virus G→A hypermutants by differential DNA denaturation PCR
Authors: Suspène Rodolphe , Henry Michel , Guillot Sophie , Wain-Hobson Simon , Vartanian Jean-Pierre
Published: December 2004

Virus genomes from the same family may exhibit a wide range in their DNA GC content, whereas viral hypermutants differ substantially in GC content from their parental genomes. As AT-rich DNA melts at lower temperatures than GC-rich DNA, use of a lower denaturation temperature during PCR should allow differential amplification of AT-rich genomes or variants within a quasispecies. The latter situation has been explored explicitly in a two-step process by using a series of well-defined viral sequences differing in their AT content. Firstly, the lowest denaturation temperature (T
p) that allowed amplification of the parental sequence was determined. Secondly, differential amplification of AT-rich viral variants was obtained by using a denaturation temperature 1–3 °C lower than T
p. Application of this sensitive method to two different viruses allowed us to identify human immunodeficiency virus type 1 G→A hypermutants in a situation where none were expected and to amplify AT-rich variants selectively within a spectrum of poliovirus mutants.