bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of Msx genes by a Bmp gradient is essential for neural crest specification
Authors: Tríbulo Celeste , Aybar Manuel J. , Nguyen Vu H. , Mullins Mary C. , Mayor Roberto
Published: November 2003

There is evidence in Xenopus and zebrafish embryos that the neural crest/neural folds are specified at the border of the neural plate by a precise threshold concentration of a Bmp gradient. In order to understand the molecular mechanism by which a gradient of Bmp is able to specify the neural crest, we analyzed how the expression of Bmp targets, the Msx genes, is regulated and the role that Msx genes has in neural crest specification.

As Msx genes are directly downstream of Bmp, we analyzed Msx gene expression after experimental modification in the level of Bmp activity by grafting a bead soaked with noggin into Xenopus embryos, by expressing in the ectoderm a dominant-negative Bmp4 or Bmp receptor in Xenopus and zebrafish embryos, and also through Bmp pathway component mutants in the zebrafish. All the results show that a reduction in the level of Bmp activity leads to an increase in the expression of Msx genes in the neural plate border. Interestingly, by reaching different levels of Bmp activity in animal cap ectoderm, we show that a specific concentration of Bmp induces msx1 expression to a level similar to that required to induce neural crest. Our results indicate that an intermediate level of Bmp activity specifies the expression of Msx genes in the neural fold region.

In addition, we have analyzed the role that msx1 plays on neural crest specification. As msx1 has a role in dorsoventral pattering, we have carried out conditional gain- and loss-of-function experiments using different msx1 constructs fused to a glucocorticoid receptor element to avoid an early effect of this factor. We show that msx1 expression is able to induce all other early neural crest markers tested (snail,slug, foxd3) at the time of neural crest specification. Furthermore, the expression of a dominant negative of Msx genes leads to the inhibition of all the neural crest markers analyzed. It has been previously shown that snail is one of the earliest genes acting in the neural crest genetic cascade. In order to study the hierarchical relationship between msx1and snail/slug we performed several rescue experiments using dominant negatives for these genes. The rescuing activity by snail and slug on neural crest development of the msx1 dominant negative, together with the inability of msx1 to rescue the dominant negatives of slug and snail strongly argue that msx1 is upstream of snail and slug in the genetic cascade that specifies the neural crest in the ectoderm. We propose a model where a gradient of Bmp activity specifies the expression of Msx genes in the neural folds, and that this expression is essential for the early specification of the neural crest.
Echinoid facilitates Notch pathway signalling duringDrosophilaneurogenesis through functional interaction with Delta
Authors: Rawlins Emma L. , Lovegrove Bridget , Jarman Andrew P.
Published: November 2003

The Notch intercellular signalling pathway is important throughout development, and its components are modulated by a variety of cellular and molecular mechanisms. Ligand and receptor trafficking are tightly controlled,although context-specific regulation of this is incompletely understood. We show that during sense organ precursor specification in Drosophila,the cell adhesion molecule Echinoid colocalises extensively with the Notch ligand, Delta, at the cell membrane and in early endosomes. Echinoid facilitates efficient Notch pathway signalling. Cultured cell experiments suggest that Echinoid is associated with the cis-endocytosis of Delta, and is therefore linked to the signalling events that have been shown to require such Delta trafficking. Consistent with this, overexpression of Echinoid protein causes a reduction in Delta level at the membrane and in endosomes. In vivo and cell culture studies suggest that homophilic interaction of Echinoid on adjacent cells is necessary for its function.
HLH-14 is aC. elegansAchaete-Scute protein that promotes neurogenesis through asymmetric cell division
Authors: Frank C. Andrew , Baum Paul D. , Garriga Gian
Published: November 2003

Achaete-Scute basic helix-loop-helix (bHLH) proteins promote neurogenesis during metazoan development. In this study, we characterize a C. elegans Achaete-Scute homolog, HLH-14. We find that a number of neuroblasts express HLH-14 in the C. elegans embryo, including the PVQ/HSN/PHB neuroblast, a cell that generates the PVQ interneuron, the HSN motoneuron and the PHB sensory neuron. hlh-14 mutants lack all three of these neurons. The fact that HLH-14 promotes all three classes of neuron indicates that C. elegans proneural bHLH factors may act less specifically than their fly and mammalian homologs. Furthermore, neural loss in hlh-14 mutants results from a defect in an asymmetric cell division: the PVQ/HSN/PHB neuroblast inappropriately assumes characteristics of its sister cell, the hyp7/T blast cell. We argue that bHLH proteins, which control various aspects of metazoan development, can control cell fate choices in C. elegans by regulating asymmetric cell divisions. Finally, a reduction in the function of hlh-2, which encodes the C. elegans E/Daughterless bHLH homolog, results in similar neuron loss as hlh-14 mutants and enhances the effects of partially reducing hlh-14 function. We propose that HLH-14 and HLH-2 act together to specify neuroblast lineages and promote neuronal fate.
A role for the polysialic acid – neural cell adhesion molecule in PDGF-induced chemotaxis of oligodendrocyte precursor cells
Authors: Zhang H. , Vutskits L. , Calaora V. , Durbec P. , Kiss J. Z.
Published: November 2003

Directed migration of oligodendrocyte precursor cells (OPCs) is important for myelin formation and repair but the mechanisms of directional control are poorly understood. Here we have tested the role of polysialic acid-neural cell adhesion molecule (PSA-NCAM) in the directional migration of OPCs towards platelet-derived growth factor (PDGF). Using a Boyden microchemotaxis chamber and the Dunn direct viewing chamber, we show that in concentration gradients of PDGF, PSA-positive OPCs polarize and efficiently migrate towards the source of PDGF (chemotaxis). The loss or inactivation of the polysialic tail of NCAM leads to an altered pattern of OPC migration in response to PDGF gradients. Cells under these conditions, while being polarized and migrating, show no bias of displacement towards the source of PDGF and make random turns. By contrast, directed migration of OPCs towards basic fibroblast growth factor was not affected by the removal of PSA. Moreover, inactivation of PSA does not interfere with the random migration pattern of cells in uniform concentrations of PDGF (chemokinesis). These results suggest that PSA-NCAM is specifically involved in establishing the directionality of OPC migration in response to the concentration gradient of PDGF, but it is not essential for cell motility per se.
Heparan sulfate proteoglycans are increased during skeletal muscle regeneration: requirement of syndecan-3 for successful fiber formation
Authors: Casar Juan Carlos , Cabello-Verrugio Claudio , Olguin Hugo , Aldunate Rebeca , Inestrosa Nibaldo C. , Brandan Enrique
Published: November 2003

Skeletal muscle regeneration is a highly complex and regulated process that involves muscle precursor proliferation and differentiation and probably requires the participation of heparin binding growth factors such as FGFs, HGF and TGFβ. Heparan sulfate proteoglycans, key components of cell-surfaces and ECM, modulate growth factor activities and influence cell growth and differentiation. Their expression in forming muscle masses during development and in cell culture, suggest their participation in the regulation of myogenesis. In the present study, heparan sulfate proteoglycan expression in skeletal muscle regeneration induced by barium chloride injection was evaluated. Expression of muscle differentiation markers and neuromuscular junction (NMJ) components was characterized. Immunoblots with anti-Δ-heparan sulfate antibody showed that four major species - perlecan, glypican, syndecan-3 and syndecan-4 - were transiently up-regulated. The first three were detected at the surface or basement membranes of newly formed myotubes by specific indirect immunofluorescence. Syndecan-3, a satellite cell marker, showed the earliest and most significant increase. Experiments involving myoblast grafting into regenerating muscle showed that C2C12 cell clones, with inhibited syndecan-3 expression resulting from antisense transfection, presented a normal proliferation rate but an impaired capacity to fuse and form skeletal muscle fibers. These data constitute the first in vivo evidence suggesting the requirement of a specific heparan sulfate proteoglycan for successful skeletal muscle regeneration.
Molecular Recognition by a Cu(II)-2,2′-bipyridine Complex Involving Coordination and Hydrogen Bonding
Authors: Kojima Takahiko , Kitaguchi Hironori , Tachi Yoshimitsu , Naruta Yoshinori , Matsuda Yoshihisa
Published: November 2003

A novel Cu(II) complex bearing a 2,2′-bipyridine derivative with malonylamide moieties showed regioselective molecular recognition behaviour toward m-aminobenzoic acid by both coordination and hydrogen bonding and this recognition should be an induced fit to the flexible recognition site of the Cu(II) complex.
Synergistic Effect of the Two Azobenzenes in the Promoter on the Photo-regulation of Transcription Reaction with SP6 RNA Polymerase
Authors: Liu Mingzhe , Tamaru Daisuke , Asanuma Hiroyuki , Komiyama Makoto
Published: November 2003

By introducing two azobenzene moieties into both RNA polymerase binding region and TATA region in the promoter of the SP6 RNA polymerase simultaneously, clear-cut photo-regulation of the transcription reaction was achieved either under dark or by UV irradiation.
Very High Cyclization Quantum Yields of Diarylethene Having Two N-Methylpyridinium Ions
Authors: Matsuda Kenji , Shinkai Yoshihiro , Yamaguchi Tadatsugu , Nomiyama Kazuko , Isayama Munetoshi , Irie Masahiro
Published: November 2003

Dithienylethenes having a pyridinium cation at one and both thiophene rings were synthesized. The derivatives with two pyridinium cation showed the cyclization quantum yield as high as 0.71, which is much larger than the values of the monocation derivative and the neutral form. This can be explained by the conformation of the open-ring isomer of the diarylethenes.
EPR Study of Photoinduced Electron Transfer between Adsorbent and Adsorbed Species in Photo-SCR with NH3
Authors: Teramura Kentaro , Tanaka Tsunehiro , Funabiki Takuzo
Published: November 2003

Photoformed hole and electron on TiO2 adsrobing NH3 are trapped, respectively, by a NH3 species adsorbed on TiO2 and Ti4+ to evolve a NH2 radical and a Ti3+ species. The photoinduced electron transfer takes place between Ti4+ and adsorbed NH3 species efficiently, resulting in the formation of a NH2 radical. The NH2 radical on TiO2 was stably present after the photoirradiation was ceased. It is quenched rapidly just after introduction of NO leaving the Ti3+ species.
Thyrotropin–Releasing Hormone in the Dorsal Vagal Complex Stimulates Hepatic Blood Flow in Rats
Authors: Yoneda Masashi , Hashimoto Takashi , Nakamura Kimihide , Tamori Keisuke , Yokohama Shiro , Kono Toru , Watanobe Hajime , Terano Akira
Published: November 2003

Central administration of thyrotropin–releasing hormone (TRH) enhances hepatic blood flow in animal models. TRH nerve fibers and receptors are localized in the dorsal vagal complex (DVC), and retrograde tracing techniques have shown that hepatic vagal nerves arise mainly from the left DVC. However, nothing is known about the central sites of action for TRH to elicit the stimulation of hepatic blood flow. The effect of microinjection of a TRH analogue into the DVC on hepatic blood flow was investigated in urethane–anesthetized rats. After measuring basal flow, a stable TRH analogue (RX–77368) was microinjected into the DVC and hepatic blood flow response was observed for 120 minutes by laser Doppler flowmetry. Either left or right cervical vagotomy or hepatic branch vagotomy was performed 2 hours before the peptide. Microinjection of RX–77368 (0.5–5 ng) into the left DVC dose–dependently increased hepatic blood flow. The stimulation of hepatic blood flow by RX–77368 microinjection into the left DVC was eliminated by left cervical and hepatic branch vagotomy but not by right cervical vagotomy. By contrast, microinjection of RX–77368 into the right DVC did not significantly alter hepatic blood flow. These results suggest that TRH acts in the left DVC to stimulate hepatic blood flow through the left cervical and hepatic vagus, indicating that neuropeptides may act in the specific brain nuclei to regulate hepatic function.
Results of Retransplantation for Recurrent Hepatitis C
Authors: Roayaie Sasan , Schiano Thomas D. , Thung Swan N. , Emre Sukru H. , Fishbein Thomas M. , Miller Charles M. , Schwartz Myron E.
Published: November 2003

Retransplantation for recurrent hepatitis C virus (HCV) has been evaluated in small series. In this study, patients undergoing transplantation for HCV–related cirrhosis with subsequent retransplantation more than 90 days for recurrent HCV (proven by pathologic examination of the explant and exclusion of other factors) were prospectively followed. This group was compared with a simultaneous cohort without HCV infection undergoing retransplantation more than 90 days after primary transplantation. Forty–two patients underwent retransplantation for recurrent HCV with a median survival of 12.9 ± 6.7 months after retransplantation. Twenty patients (48%) were dead at 6 months, and 13 (65%) of these deaths were due to sepsis. On univariate analysis, creatinine level greater than or equal to 3 mg/dL, platelet count less than 100,000/μL, prothrombin time (PT) greater than or equal to 16 seconds, alkaline phosphatase level less than or equal to 240 U/L, γ–glutamyltransferase level less than or equal to 130 U/L, and donor age of 60 years or greater all correlated significantly with shorter survival after retransplantation. PT and donor age were predictors of survival on multivariate analysis. Patients undergoing retransplantation for recurrent HCV had a significantly shorter median survival than the 55 patients undergoing retransplantation for other chronic reasons of graft loss (75.6 ± 17.7 months). In conclusion, median survival after liver retransplantation for recurrent HCV is significantly shorter than after retransplantation for other causes of late graft loss. Most deaths occur in the first 6 months and are due to sepsis. Candidates for retransplantation with a preoperative PT less than 16 seconds and those receiving grafts from donors younger than 60 years can expect a significantly longer median survival after retransplantation.
A Key Pathogenic Role for the Stat1/T–Bet Signaling Pathway in T–Cell-Mediated Liver Inflammation
Authors: Siebler Jürgen , Wirtz Stefan , Klein Sonja , Protschka Martina , Blessing Manfred , Galle Peter R. , Neurath Markus F.
Published: November 2003

TH1 cytokines have been suggested to contribute to the pathogenesis of T–cell–mediated liver injury and inflammation. However, the molecular signaling pathways involved in such injury are still poorly understood. In the present study, we investigated the role of the STAT1/T–bet signaling pathway in a murine model of T–cell–mediated liver inflammation induced by the application of concanavalin A (Con A) using newly created STAT1 transgenic mice as well as STAT1– and T–bet–deficient mice. Liver injury induced by Con A was associated with an increase of both pSTAT1 and T–bet levels in the liver. Furthermore, functional studies suggested a pathogenic role for STAT1 in Con A–induced liver injury, because transgenic mice overexpressing STAT1 under the control of the CD2 promoter/enhancer construct showed elevated interferon gamma (IFN–γ) and IRF–1 levels as well as significantly augmented liver injury following administration of Con A. Consistently, we observed that both STAT1–deficient and T–bet–deficient mice were protected from such T–cell–dependent liver injury. In conclusion, these findings suggest a key pathogenic role for the STAT1/T–bet signaling pathway for T–cell activation in the Con A model of T–cell–mediated liver pathology.
In situ forces of the anterior and posterior cruciate ligaments in high knee flexion: An in vitro investigation
Authors: Li Guoan , Zayontz Shay , Most Ephrat , DeFrate Louis E. , Suggs Jeremy F. , Rubash Harry E.
Published: November 2003

The function of the anterior and posterior cruciate ligaments (ACL and PCL) in the first 120° of flexion has been reported extensively, but little is known of their behavior at higher flexion angles. The aim of this investigation was to study the effects of muscle loads on the in situ forces in both ligaments at high knee flexion (> 120°). Eighteen fresh‐frozen human knee specimens were tested on a robotic testing system from full extension to 150° of flexion in response to quadriceps (400 N), hamstrings (200 N), and combined quadriceps and hamstrings (400 N/200 N) loads. The in situ forces in the ACL and PCL were measured using the principle of superposition. The force in the ACL peaked at 30° of flexion (71.7 ± 27.9 N in response to the quadriceps load, 52.3 ± 24.4 N in response to the combined muscle load, 32.3 ± 20.9 N in response to the hamstrings load). At 150°, the ACL force was approximately 30 N in response to the quadriceps load and 20 N in response to the combined muscle load and isolated hamstring load. The PCL force peaked at 90° (34.0 ± 15.3 N in response to the quadriceps load, 88.6 ± 23.7 N in response to the combined muscle load, 99.8 ± 24.0 N in response to the hamstrings load) and decreased to around 35 N at 150° in response to each of the loads.

These results demonstrate that the ACL and PCL carried significantly less load at high flexion in response to the simulated muscle loads compared to the peak loads they carried in response to the same muscle loads at other flexion angles. The data could provide a reference point for the investigation of non‐weight bearing flexion and extension knee exercises in high flexion. Furthermore, these data could be useful in designing total knee implants to achieve high flexion. © 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
Effects of timing of low‐intensity pulsed ultrasound on distraction osteogenesis
Authors: Sakurakichi Keisuke , Tsuchiya Hiroyuki , Uehara Kenji , Yamashiro Teruhisa , Tomita Katsuro , Azuma Yoshiaki
Published: November 2003

We investigated the effects of low‐intensity pulsed ultrasound (LIPUS; 30 mW/cm2 spatial and temporal average) on the timing of LIPUS treatment in distraction osteogenesis. Lengthening of the right tibia was performed in 75 male Japanese white rabbits using unilateral fixators (waiting period, 7 days; distraction rate, 1.5 mm/day; distraction period, 7 days). Rabbits were divided into four groups according to the timing of the LIPUS treatment. Control group had no stimulation. Waiting group was treated with a daily 20‐min session of LIPUS during a 7‐day latency period. Lengthening group was treated during the lengthening period. Maturation group was treated for the first 7 days after completion of distraction. We evaluated the distraction site by radiography and histology every week for 4 weeks. Bone mineral density (BMD) and mechanical strength were tested and microfocus X‐ray computed tomography was performed on specimens 2 weeks after completion of distraction. The lengthening group had greater BMD and mechanical strength than the other groups, bone regeneration was enhanced more in the maturation group than in the control or waiting groups. Histologically, endochondral bone formation in the lengthening and the maturation groups occurred earlier than in the control or waiting groups. These results suggest the LIPUS effect is mediated via endochondral pathways. We concluded that LIPUS stimulates bone formation in distraction osteogenesis and is most effective during the lengthening phase. © 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
Introduction
Authors: Atabaki Touraj , van der Linden Marcel
Published: November 2003

In its long history Iran has experienced many eventful moments. The past century was far from exceptional in this respect: the country was ravaged by three major wars (1914–1918, 1941–1945, 1980–1988) in which hundreds of thousands of people died; two coups (1921, 1953) transformed power relations within the political and military elite; and two revolutions (1905–1911, 1978–1979) led to radical changes in social, cultural, and political relationships. The country's appearance has changed completely since the end of the nineteenth century. At the beginning of the twentieth century, a large proportion of the population lived in tribal communities; by the end of the century the central state was omnipresent. The capital, Tehran, expanded from a city of around 100,000 inhabitants in 1890 to a metropolis of over ten million.
Democracy and Historiographies of Organized Labour in Zimbabwe
Authors: Barnes Teresa
Published: November 2003

Keep on Knocking: A History of the Labour Movement in Zimbabwe, 1900–97. Ed. by Brian Raftopoulos and Ian Phimister. Baobab Books on behalf of the Zimbabwe Congress of Trade Unions and the Friedrich Ebert Stiftung, Harare 1997. xx, 164 pp.

Striding Back: The Labour Movement and the Post-Colonial State in Zimbabwe 1980–2000. Ed. by Brian Raftopoulos and Lloyd Sachikonye. Weaver Press, Harare 2001. xxvii, 316 pp., £14.95; $24.95.
Mutiny in Comparative Perspective
Authors: Lammers Cornelis J.
Published: November 2003

Rebellion, Repression, Reinvention. Mutiny in Comparative Perspective. Ed. by Jane Hathaway. Foreword by Geoffrey Parker. Praeger, Westport (Conn.) [etc.] 2001. xix, 282 pp. Maps. £56.95.
Ritual Kissing, Heresy and the Emergence of Early Christian Orthodoxy
Authors: PENN MICHAEL
Published: November 2003

Amidst the theological controversies of the fourth and fifth centuries, the ritual kiss often played an important role in trying to distinguish orthodox from heretical Christians. For early Christian leaders such as Rufinus, Jerome, Augustine and Paulinus of Nola, the kiss became a means to malign an opponent while simultaneously reinforcing one's own claims to theological legitimacy. The kiss's connection to a wide range of symbolic systems made it a particularly versatile tool for early Christian polemics.
PROPORTIONATE TAXATION AS A FAIR DIVISION OF THE SOCIAL SURPLUS: THE STRANGE CAREER OF AN IDEA
Authors: Fried Barbara H.
Published: November 2003

The article considers a surprisingly resilient argument, going back to Adam Smith, for the fairness of proportionate taxation: that proportionate taxation represents the fair way to divide the surplus value produced by social cooperation among all of society's members. The article considers two recent variants on that argument, one by Richard Epstein in Takings and one by David Gauthier in Morals by Agreement. It concludes that the normative and empirical assumptions that underlie these, and all other variants, of the argument are so implausible as to suggest the argument cannot be taken seriously as a defense of proportionate taxation. The article concludes by considering other possible explanations for the enduring attraction of proportionate taxation for political philosophers, particularly those with libertarian and quasi-libertarian leanings.
A Late Cretaceous paleomagnetic pole from Koto rhyolite, southwest Japan: Implications for eastern margin deformation of Asia
Authors: Fukuma Koji , Tsurudome Hisashi , Torii Masayuki
Published: November 2003

A paleomagnetic pole was obtained from Late Cretaceous rhyolitic ash flow tuffs and associated ring dikes, which are collectively called the Koto rhyolite in the eastern part of southwest Japan. Characteristic remanent magnetizations were isolated from 33 sites through thermal demagnetization. Normal and reversed polarity magnetizations were found and are mutually antipodal. Although the magnetization directions become more dispersed after tilt correction, the clearly defined polarity sequence and the positive contact test between ash flow tuffs and ring dikes ensure that the characteristic magnetizations of ash flow tuffs predate the intrusion of associated ring dikes. Since no regional tilting is expected, we regard the in situ magnetization directions to represent the Late Cretaceous (70 Ma) paleomagnetic field (D = 84.6°, I = 57.5°, α95 = 5.5°) in eastern southwest Japan. The paleomagnetic pole is not significantly different from the coeval poles of western southwest Japan. This result gives a further support to a microplate model for the Miocene clockwise rotation of southwest Japan. By canceling out the effect of the Miocene rotation, we were able to obtain a paleomagnetic pole of 70 Ma (219.7°E, 63.0°N, α95 = 12.2°) for southwest Japan when the Japan Arc was incorporated in the eastern margin of Asia. Paleomagnetic poles of Late Cretaceous age from Korea, south China coast, and restored southwest Japan are statistically indistinguishable from each other but significantly differ from that of the continental interior of east Asia. The observed rotation of about 20° probably results from shear deformation exerted by northeast‐trending strike‐slip faults along the eastern continental margin of Asia.
The second law of thermodynamics and the global climate system: A review of the maximum entropy production principle
Authors: Ozawa Hisashi , Ohmura Atsumu , Lorenz Ralph D. , Pujol Toni
Published: November 2003

The long‐term mean properties of the global climate system and those of turbulent fluid systems are reviewed from a thermodynamic viewpoint. Two general expressions are derived for a rate of entropy production due to thermal and viscous dissipation (turbulent dissipation) in a fluid system. It is shown with these expressions that maximum entropy production in the Earth's climate system suggested by Paltridge, as well as maximum transport properties of heat or momentum in a turbulent system suggested by Malkus and Busse, correspond to a state in which the rate of entropy production due to the turbulent dissipation is at a maximum. Entropy production due to absorption of solar radiation in the climate system is found to be irrelevant to the maximized properties associated with turbulence. The hypothesis of maximum entropy production also seems to be applicable to the planetary atmospheres of Mars and Titan and perhaps to mantle convection. Lorenz's conjecture on maximum generation of available potential energy is shown to be akin to this hypothesis with a few minor approximations. A possible mechanism by which turbulent fluid systems adjust themselves to the states of maximum entropy production is presented as a self‐feedback mechanism for the generation of available potential energy. These results tend to support the hypothesis of maximum entropy production that underlies a wide variety of nonlinear fluid systems, including our planet as well as other planets and stars.
Reply to comment by F. Feser et al. on ‘Improved global maps and 54‐year history of wind‐work on ocean inertial motions’
Authors: Alford Matthew H.
Published: November 2003

In their comment, Feser et al. [2003] argue that the NCEP Reanalysis surface winds used by Alford [2003; henceforth A03] are artificially high at high frequencies due to temporal aliasing. This possibility is investigated here by direct comparison with buoy winds in the northeastern Atlantic. As in a previous more extensive buoy comparison in the Pacific [Alford, 2001; henceforth A01], no evidence for aliasing of NCEP winds is found.
Indication of active overthrust faulting along the Holocene‐Wisconsin transition in the marginal zone of Jakobshavn Isbræ
Authors: Lüthi M. P. , Funk M. , Iken A.
Published: November 2003

A zone of highly irregular ice motion has been detected within the ice sheet adjacent to Jakobshavn Isbræ, a fast moving ice stream in West Greenland. Two tilt sensors in different boreholes and frozen into the ice show angle variations of up to 0.1° and 0.3° within a 1200 s interval. The amplitude of these flutter oscillations increases toward the transition from Holocene to Wisconsin ice at 682 m depth, 150 m above bedrock. All other tilt sensors above and below show low background noise. A numerical model confirms that the stress configuration is exceptional in the neighborhood of the ice stream. Stress transfer from the ice stream to the margins causes an extra forcing of the basal ice at the drill site. Several possible explanations for the observed flutter oscillations are given, the most likely being dynamic rupture events or stick‐slip motion along the Holocene‐Wisconsin transition. If true, this would correspond to an active overthrust fault with very high loading rates.
Snow process modeling in the North American Land Data Assimilation System (NLDAS): 2. Evaluation of model simulated snow water equivalent
Authors: Pan Ming , Sheffield Justin , Wood Eric F. , Mitchell Kenneth E. , Houser Paul R. , Schaake John C. , Robock Alan , Lohmann Dag , Cosgrove Brian , Duan Qingyun , Luo Lifeng , Higgins R. Wayne , Pinker Rachel T. , Tarpley J. Dan
Published: November 2003

This is the second part of a study on the cold season process modeling in the North American Land Data Assimilation System (NLDAS). The first part concentrates on the assessment of model simulated snow cover extent. In this second part, the focus is on the evaluation of simulated snow water equivalent (SWE) from the four land surface models (Noah, MOSAIC, SAC and VIC) in the NLDAS. Comparisons are made with observational data from the Natural Resources Conservation Service's Snowpack Telemetry (SNOTEL) network for a 3‐year retrospective period at selected sites in the mountainous regions of the western United States. All models show systematic low bias in the maximum annual simulated SWE that is most notable in the Cascade and Sierra Nevada regions where differences can approach 1000 mm. Comparison of NLDAS precipitation forcing with SNOTEL measurements revealed a large bias in the NLDAS annual precipitation which may be lower than the SNOTEL record by up to 2000 mm at certain stations. Experiments with the VIC model indicated that most of the bias in SWE is removed by scaling the precipitation by a regional factor based on the regression of the NLDAS and SNOTEL precipitation. Individual station errors may be reduced further still using precipitation scaled to the local station SNOTEL record. Furthermore, the NLDAS air temperature is shown to be generally colder in winter months and biased warmer in spring and summer when compared to the SNOTEL record, although the level of bias is regionally dependent. Detailed analysis at a selected station indicate that errors in the air temperature forcing may cause the partitioning of precipitation into snowfall and rainfall by the models to be incorrect and thus may explain some of the remaining errors in the simulated SWE.
The Structure of 1,3-Enaminoketonatoboron Difluorides in Solution and in the Solid State
Authors: Itoh Kuniaki , Okazaki Kazuhiko , Fujimoto Miki
Published: November 2003

Nuclear magnetic resonance, infrared, and ultraviolet spectra and X-ray analysis of three 1,3-enaminoketonatoboron difluorides (BF2 complexes, (2a)–(2c)) both in solution and in the solid state have been recorded. Their structures are discussed in relation to the electron distribution in their chelate rings and in comparison with those of their parent compounds (1a)–(1c) and 1,3-diketonatoboron difluorides. C1 and C3 chemical shifts in the 13C NMR spectra indicated that the ketoamine and enolimine tautomeric forms may be present in equal amounts. Additionally, the phenyl groups participate in the delocalized π-electron system of the chelate ring. On the other hand, in the solid state, a comparison of the bond lengths by X-ray analysis provides information on processes occurring as contribution of the enolimine form increases. The information found may offer valuable suggestions for the reactivity and the structure of the products for the reactions of the BF2 complexes.
Review: Highly Selective Compounds for the Antibody-Directed Enzyme Prodrug Therapy of Cancer
Authors: Tietze Lutz F. , Feuerstein Tim
Published: November 2003

Antibody-directed enzyme prodrug therapy (ADEPT) is a recent development for a selective treatment of cancer, based on site-directed formation at the surface of malignant cells of cytotoxic compounds from non-toxic prodrugs with a conjugate of an appropriate enzyme and a monoclonal antibody which binds to tumour-associated antigens. New potent prodrugs of analogues of the antibiotic CC-1065 have been developed. These show a remarkable selectivity with a Q(IC50) value of up to more than 3000. Moreover, the formed drug has a high potency with an IC50 of 30 pM.
Regioselective Anomeric Deacetylation of Peracetylated Glycopyranoses
Authors: Bhaumik Kankan , Salgaonkar Paresh D. , Akamanchi K. G.
Published: November 2003

A simple and mild method for regioselective anomeric deacetylation of peracetylated glycopyranoses using copper(II) acetate dihydrate and methanol/water (9 : 1) is described.
Recent Advances in NMR Diffusion Techniques for Studying Drug Binding
Authors: Price William S.
Published: November 2003

Characterizing the binding of ligands to macromolecular receptors in solution is important to many areas of chemistry, biology, and nanobiotechnology, but perhaps most notably to drug development. NMR has proven to be particularly useful for such studies, but the systems studied have generally been restricted to model systems with dubious physiological relevance. This paper reviews the use of NMR diffusion measurements to study drug binding and two recent advances that enable measurements to be conducted in more sensitive higher-field NMR spectrometers in non-deuterated aqueous samples.
Stereochemistry and Crystal Structures of Bis Cycloadducts of Danishefsky's Diene (Me3SiOC(=CH2)CH=CHOMe) with 2,5- and 2,6-Dichlorobenzoquinone
Authors: Cameron Donald W. , Evans Raymond L. , Feutrill Geoffrey I. , Patrick Vincent A. , Skelton Brian W. , White Allan H.
Published: November 2003

Syntheses and single crystal X-ray structural characterizations are reported for bis adducts (6) and (7) formed between Danishefsky's diene (8) with (respectively) the dienophiles 2,6- and 2,5-dichlorobenzoquinone. Formation of each adduct involves diastereocontrolled creation of six stereogenic centres.
Glasshouse and field studies on the effects of groundcovers on banana and macadamia growth and water relations
Authors: Firth D. J. , Johns G. G. , Whalley R. D. B.
Published: November 2003

Groundcovers can be useful for controlling erosion in macadamia orchards but they can have adverse effects on tree growth and crop yield. The effects of groundcovers versus bare soil on banana and macadamia were compared in a glasshouse study and on macadamia in the field. A glasshouse trial compared the effect of 3 water regimes with unmown or mown Arachis pintoi cv. Amarillo groundcover versus bare soil, on stomatal conductance and growth of banana and macadamia. Mean stomatal conductance was higher overall for macadamia (178 mmol/m2.s) compared with banana (90 mmol/m2.s) when data were pooled across groundcover and water treatments. Medium and dry substrate moisture treatments significantly reduced the growth and vigour of banana compared with the wet treatments, as indicated by reduced total dry matter, leaf area, number of live leaves at harvest, and total root length, but had no significant effect on macadamia. Groundcover had a more adverse effect on the growth of banana than macadamia compared with bare soil and, likewise, unmown cover had a greater effect on growth of banana than mown cover, while there was no mowing effect on macadamia.In an unirrigated field trial, mown and unmown groundcover and bare soil treatments were compared for their effect on early morning leaf xylem water potential of young and older macadamia trees at 3 sites where groundcover was established at different tree ages. Water potential was generally <0.2 MPa more negative in the groundcover treatment than bare soil in spring and summer under dry seasonal conditions over 2 years, although there was no apparent effect on tree health. The difference in water potential between groundcover and bare soil was highest in young trees planted in established groundcover. The more adverse effect of groundcover on water status of young trees in established cover correlates with a greater reduction in growth compared with older trees reported separately (Firth et al. 2003 Aust. J. Exp. Agric. 43, 419–423).Soil bulk density under groundcover was slightly reduced (0.028 g/cm3) at 0–10 cm depth, and penetrometer resistance also slightly reduced (<0.3 MPa) at 0–12 cm depth, compared with bare soil. Higher penetrometer readings in the traffic zone (often >4 MPa at 30–40 cm in the initial survey) compared with the tree line indicate the potential long-term benefits to be derived from groundcovers.
Constitutive expression of Vitis vinifera thaumatin-like protein after in vitro selection and its role in anthracnose resistance
Authors: Jayasankar Subramanian , Li Zhijian , Gray Dennis J.
Published: November 2003

Anthracnose-resistant grapevine (Vitis vinifera L. cv. Chardonnay) plants were regenerated from embryogenic cultures that had been subjected to in vitro selection with culture filtrate of Elsinoe ampelina (de Bary) Shear. Three secreted proteins differentially expressed by in vitro-selected embryogenic cultures and regenerated plants were identified. An 8-kDa protein was identified as a lipid-transfer protein (LTP) by N-terminal amino acid sequence comparison. Two other differentially expressed proteins, with estimated molecular weights of 21.6 and 22�kDa, immuno-reacted with antiserum raised against a thaumatin-like protein (TLP) protein from pinto bean (Phaseolus vulgaris L.). N-terminal amino acid sequencing of the 21.6-kDa protein showed a high degree of homology to V. vinifera thaumatin-like protein 2 (VVTL-2 = grapevine osmotin; Acc no. CAA71883), and that of the 22-kDa protein was homologous to V. vinifera thaumatin-like protein 1 (VVTL-1; AAB61590). Interestingly, both VVTL-1 and VVTL-2 are pathogenesis-related (PR) proteins, belonging to the PR-5 group. Protein produced from the cloned grapevine VVTL-1 gene significantly inhibited E. ampelina spore germination and hyphal growth in vitro. Plants regenerated from in vitro-selected cultures similarly inhibited fungal growth in vivo. Enhanced expression of antifungal VVTL-1 in anthracnose resistant grapevine strongly suggests that it plays an important role, either alone or in conjunction with other PR proteins, by suppressing pathogen growth.
Spermidine but not spermine is essential for hypusine biosynthesis and growth in
Saccharomyces cerevisiae
: Spermine is converted to spermidine
in vivo
by the
FMS1
-amine oxidase
Authors: Chattopadhyay Manas K. , Tabor Celia White , Tabor Herbert
Published: November 2003

In our earlier work we showed that either spermidine or spermine could support the growth of s
pe2
Δ or s
pe3
Δ polyamine-requiring mutants, but it was unclear whether the cells had a specific requirement for either of these amines. In the current work, we demonstrate that spermidine is specifically required for the growth of
Saccharomyces cerevisiae
. We were able to show this specificity by using a
spe3
Δ
fms1
Δ mutant that lacked both spermidine synthase and the
FMS1
-encoded amine oxidase that oxidizes spermine to spermidine. The polyamine requirement for the growth of this double mutant could only be satisfied by spermidine; i.e., spermine was not effective because it cannot be oxidized to spermidine in the absence of the
FMS1
gene. We also showed that at least one of the reasons for the absolute requirement for spermidine for growth is the specificity of its function as a necessary substrate for the hypusine modification of eIF5A. Spermine itself cannot be used for the hypusine modification, unless it is oxidized to spermidine by the Fms1 amine oxidase. We have quantified the conversion of spermine
in vivo
and have shown that this conversion is markedly increased in a strain overexpressing the Fms1 protein. We have also shown this conversion in enzymatic studies by using the purified amine oxidase from yeast.
Synergy and contingency as driving forces for the evolution of multiple secondary metabolite production by
Streptomyces
species
Authors: Challis Gregory L. , Hopwood David A.
Published: November 2003

In this article we briefly review theories about the ecological roles of microbial secondary metabolites and discuss the prevalence of multiple secondary metabolite production by strains of
Streptomyces
, highlighting results from analysis of the recently sequenced
Streptomyces coelicolor
and
Streptomyces avermitilis
genomes. We address this question: Why is multiple secondary metabolite production in
Streptomyces
species so commonplace? We argue that synergy or contingency in the action of individual metabolites against biological competitors may, in some cases, be a powerful driving force for the evolution of multiple secondary metabolite production. This argument is illustrated with examples of the coproduction of synergistically acting antibiotics and contingently acting siderophores: two well-known classes of secondary metabolite. We focus, in particular, on the coproduction of β-lactam antibiotics and β-lactamase inhibitors, the coproduction of type A and type B streptogramins, and the coregulated production and independent uptake of structurally distinct siderophores by species of
Streptomyces
. Possible mechanisms for the evolution of multiple synergistic and contingent metabolite production in
Streptomyces
species are discussed. It is concluded that the production by
Streptomyces
species of two or more secondary metabolites that act synergistically or contingently against biological competitors may be far more common than has previously been recognized, and that synergy and contingency may be common driving forces for the evolution of multiple secondary metabolite production by these sessile saprophytes.
Coevolution of an aminoacyl-tRNA synthetase with its tRNA substrates
Authors: Salazar Juan C. , Ahel Ivan , Orellana Omar , Tumbula-Hansen Debra , Krieger Robert , Daniels Lacy , Söll Dieter
Published: November 2003

Glutamyl-tRNA synthetases (GluRSs) occur in two types, the discriminating and the nondiscriminating enzymes. They differ in their choice of substrates and use either tRNA
Glu
or both tRNA
Glu
and tRNA
Gln
. Although most organisms encode only one GluRS, a number of bacteria encode two different GluRS proteins; yet, the tRNA specificity of these enzymes and the reason for such gene duplications are unknown. A database search revealed duplicated GluRS genes in >20 bacterial species, suggesting that this phenomenon is not unusual in the bacterial domain. To determine the tRNA preferences of GluRS, we chose the duplicated enzyme sets from
Helicobacter pylori
and
Acidithiobacillus ferrooxidans
.
H. pylori
contains one tRNA
Glu
and one tRNA
Gln
species, whereas
A. ferrooxidans
possesses two of each. We show that the duplicated GluRS proteins are enzyme pairs with complementary tRNA specificities. The
H. pylori
GluRS1 acylated only tRNA
Glu
, whereas GluRS2 was specific solely for tRNA
Gln
. The
A. ferrooxidans
GluRS2 preferentially charged

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. Conversely,
A. ferrooxidans
GluRS1 glutamylated both tRNA
Glu
isoacceptors and the

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species. These three tRNA species have two structural elements in common, the augmented D-helix and a deletion of nucleotide 47. It appears that the discriminating or nondiscriminating natures of different GluRS enzymes have been derived by the coevolution of protein and tRNA structure. The coexistence of the two GluRS enzymes in one organism may lay the groundwork for the acquisition of the canonical glutaminyl-tRNA synthetase by lateral gene transfer from eukaryotes.
Cellulosome assembly revealed by the crystal structure of the cohesin–dockerin complex
Authors: Carvalho Ana L. , Dias Fernando M. V. , Prates José A. M. , Nagy Tibor , Gilbert Harry J. , Davies Gideon J. , Ferreira Luís M. A. , Romão Maria J. , Fontes Carlos M. G. A.
Published: November 2003

The utilization of organized supramolecular assemblies to exploit the synergistic interactions afforded by close proximity, both for enzymatic synthesis and for the degradation of recalcitrant substrates, is an emerging theme in cellular biology. Anaerobic bacteria harness a multiprotein complex, termed the “cellulosome,” for efficient degradation of the plant cell wall. This megadalton catalytic machine organizes an enzymatic consortium on a multifaceted molecular scaffold whose “cohesin” domains interact with corresponding “dockerin” domains of the enzymes. Here we report the structure of the cohesin–dockerin complex from
Clostridium thermocellum
at 2.2-Å resolution. The data show that the β-sheet cohesin domain interacts predominantly with one of the helices of the dockerin. Whereas the structure of the cohesin remains essentially unchanged, the loop–helix–helix–loop–helix motif of the dockerin undergoes conformational change and ordering compared with its solution structure, although the classical 12-residue EF-hand coordination to two calcium ions is maintained. Significantly, internal sequence duplication within the dockerin is manifested in near-perfect internal twofold symmetry, suggesting that both “halves” of the dockerin may interact with cohesins in a similar manner, thus providing a higher level of structure to the cellulosome and possibly explaining the presence of “polycellulosomes.” The structure provides an explanation for the lack of cross-species recognition between cohesin–dockerin pairs and thus provides a blueprint for the rational design, construction, and exploitation of these catalytic assemblies.
J protein cochaperone of the mitochondrial inner membrane required for protein import into the mitochondrial matrix
Authors: D'Silva Patrick D. , Schilke Brenda , Walter William , Andrew Amy , Craig Elizabeth A.
Published: November 2003

The major Hsp70 of the mitochondrial matrix (Ssc1 in yeast) is critically important for the translocation of proteins from the cytosol, across the mitochondrial inner membrane, and into the matrix. Tim44, a peripheral inner membrane protein with limited sequence similarity to the J domain of J-type cochaperones, tethers Ssc1 to the import channel. Here we report that, unlike a J protein, Tim44 does not stimulate the ATPase activity of Ssc1, nor does it affect the stimulation by either a known mitochondrial J protein or a peptide substrate. Thus, we conclude that Tim44 does not function as a J protein cochaperone of Ssc1; rather, it tethers Ssc1 to the import channel through interactions independent of those critical for J protein function. However, a previously unstudied essential gene,
PAM18
, encodes an 18-kDa protein that contains a J domain and is localized to the mitochondrial inner membrane. Pam18 stimulates the ATPase activity of Ssc1; depletion of Pam18
in vivo
disrupts import of proteins into the mitochondrial matrix. We propose that Pam18 is the J protein partner for Ssc1 at the import channel and is critical for Ssc1's function in protein import.