bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal evaluation of methionine synthase and related metabolites in the MAC15A mouse adenocarcinoma animal model
Authors: Blackburn Alison , Bibby Michael C. , Lucock Mark D. , Nicolaou Anna 
Published: June 2004

AbstractMethionine dependence is unique to cancer cells and defined as the inability to grow in a methionine‐deprived environment even if supplemented with the metabolic precursor homocysteine. Cobalamin‐dependent methionine synthase (MS) catalyses the formation of methionine and tetrahydrofolate from homocysteine and methyltetrahydrofolate, thus linking the methionine and folate pathways. The apparent altered methionine metabolism in methionine‐dependent cancer cells suggests a role for MS, although results to date are conflicting. We have analysed key metabolites of the MS‐associated transmethylation, transsulphuration and folate pathways of the methionine‐dependent MAC15A tumour model as a function of tumour progression over a 10‐day period. MS activity increased 2‐fold from day 1 to day 10. Cysteine, homocysteine, S‐adenosylmethionine and S‐adenosylhomocysteine levels in tumour cytosolic fractions decreased as a function of tumour progression. Plasma cysteine levels also decreased, whilst the distribution of folates in erythrocytes was altered, with a maximum increase in methyltetrahydrofolate observed by day 5. The increasing MS activity and decreasing cysteine levels suggest an increasing methionine requirement by the tumour, whilst the induction of enzyme activity indicates that MS is not defective in the methionine‐dependent MAC15A tumour. The decrease in tumour S‐adenosylmethionine and S‐adenosylhomocysteine levels suggests that methionine is required for some function other than cellular methylation, e.g., incorporation into protein. Overall, the results support a theory of methionine conservation in response to tumour growth, where the methionine‐dependent MAC15A tumour has a higher than normal methionine requirement. © 2004 Wiley‐Liss, Inc.
Binding and interstitial penetration of liposomes within avascular tumor spheroids
Authors: Kostarelos Kostas , Emfietzoglou Dimitris , Papakostas Alexandros , Yang Wei‐Hong , Ballangrud Åse , Sgouros George 
Published: June 2004

AbstractThe liposomal delivery of cancer therapeutics, including gene therapy vectors, is an area of intense study. Poor penetration of liposomes into interstitial tumor spaces remains a problem, however. In this work, the penetration of different liposomal formulations into prostate carcinoma spheroids was examined. Spheroid penetration was assessed by confocal microscopy of fluorescently labeled liposomes. The impact of liposomal surface charge, mean diameter, lipid bilayer fluidity and fusogenicity on spheroid penetration was examined. A variety of different liposome systems relevant to clinical or preclinical protocols have been studied, including classical zwitterionic (DMPC:chol) and sterically stabilized liposomes (DMPC:chol:DOPE‐PEG2000), both used clinically, and cationic liposomes (DMPC:DOPE:DC‐chol and DOTAP), forming the basis of the vast majority of nonviral gene transfer vectors tested in various cancer trials. Surface interactions between strongly cationic vesicles and the tumor cells led to an electrostatically derived binding‐site barrier effect, inhibiting further association of the delivery systems with the tumor spheroids (DMPC:DC‐chol). However, inclusion of the fusogenic lipid DOPE and use of a cationic lipid of lower surface charge density (DOTAP instead of DC‐chol) led to improvements in the observed intratumoral distribution characteristics. Sterically stabilized liposomes did not interact with the tumor spheroids, whereas small unilamellar classical liposomes exhibit extensive distribution deeper into the tumor volume. Engineering liposomal delivery systems with a relatively low charge molar ratio and enhanced fusogenicity, or electrostatically neutral liposomes with fluid bilayers, offered enhanced intratumoral penetration. This study shows that a delicate balance exists between the strong affinity of delivery systems for the tumor cells and the efficient penetration and distribution within the tumor mass, similar to previous work studying targeted delivery by ligand‐receptor interactions of monoclonal antibodies. Structure‐function relationships from the interaction of different liposome systems with 3‐dimensional tumor spheroids can lead to construction of delivery systems able to target efficiently and penetrate deeper within the tumor interstitium and act as a screening tool for a variety of therapeutics against cancer. © 2004 Wiley‐Liss, Inc.
Transition to College: What Helps At‐Risk Students and Students Whose Parents Did Not Attend College
Authors: Choy Susan P. , Horn Laura J. , Nuñez Anne‐Marie , Chen Xianglei 
Published: June 2004

AbstractThis chapter investigates factors that facilitate postsecondary enrollment for subpopulations of high school students. Students that find themselves at risk and those with parents who have no college experience receive primary consideration.
How Do Student Ratings Measure Up to a New Validity Framework?
Authors: Ory John C. , Ryan Katherine 
Published: June 2004

AbstractThe authors examine student ratings within a new framework that emphasizes six distinct aspects of validity: content, substantive, structural, generalizability, external, and consequential. They conclude that greater attention should be directed toward consequential validity, particularly the matters of how ratings are used on today's campuses and what happens as a result.
Ub on the move
Authors: Shcherbik Natalia , Haines Dale S. 
Published: June 2004

AbstractUbiquitination is an increasingly common post‐translation modification that controls both the expression and activity of numerous proteins in the eukaryotic cell. One frequent target of the ubiquitin (Ub) modification machinery is transcription factors. Although ubiquitination generally modulates their function by inducing proteasome‐dependent degradation, past and recent studies indicate that ubiquitination also regulates nuclear–cytoplasmic trafficking of transcriptional regulators. Ubiquitination is known to modulate transcription factor localization by destroying sequestering proteins and by directly promoting nuclear import and export of modified substrates. This review discusses old and new paradigms relating Ub modification and the control of transcription factor shuttling in and out of the nucleus. © 2004 Wiley‐Liss, Inc.
Non‐thermal effects of electromagnetic fields at mobile phone frequency on the refolding of an intracellular protein: Myoglobin
Authors: Mancinelli Fabrizio , Caraglia Michele , Abbruzzese Alberto , d'Ambrosio Guglielmo , Massa Rita , Bismuto Ettore 
Published: June 2004

AbstractNon‐thermal effects induced by exposure to microwave electromagnetic field (MW‐EMF) at 1.95 MHz, a frequency used in mobile communication, have been observed on the refolding kinetics of the heme binding site in an intracellular protein: tuna myoglobin, starting from acidic conditions. We have selected myoglobin because it can be considered a good model to study protein interactions with MW‐EMF for its well‐known high‐resolution crystallographic structure. Myoglobin solutions at pH 3.0 were subjected to 3 h exposure to microwave field (with a specific absorption rate of 51 ± 1 mW/g); the heme site refolding has been followed by measuring the molecular absorption in the Soret spectral region and the data were fitted to a bi‐exponential model. The kinetics of exposed samples appear to be slowered by MW‐EMF action. Moreover, the tryptophanyl lifetime distribution of the exposed protein, as deduced by the analysis of the fluorescence emission decay from its single tryptophan, appears sharper if compared to non‐exposed protein samples. This observation suggests that the presence of MW‐EMF could affect the propensity of protein molecules to populate specific conformational substates among which myoglobin molecules fluctuate at acidic pH. Changes in the structural fluctuation caused by MW perturbation can affect differently the aggregation process that occurs competitively during the protein folding, so representing a potential risk for protein “misfolding.” These data suggest that MW‐EMF could have also biochemical and, consequently, biological effects on eukaryotic cells that are still under investigation. © 2004 Wiley‐Liss, Inc.
Role of serotonin, γ‐aminobutyric acid, and glutamate in the behavioral thermoregulation of female tilapia during the prespawning phase
Authors: Tsai Ching‐Lin , Wang Li‐Hsueh , Tsai Chia‐Chiun 
Published: June 2004

AbstractThe role of hypothalamic neurotransmitter systems in behavioral thermoregulation was investigated in the prespawning female tilapia, Oreochromis mossambicus. Intrahypothalamic microinjection with serotonin (5‐HT, 3 µl of 1.0×10−6 M) resulted in a significant increase in the selected temperature. This effect was mimicked by the agonist of 5‐HT1A, 1B, and 2C receptors, N‐3‐trifluoromethylphenyl piperazine. Intrahypothalamic microinjection of tilapia with γ‐aminobutyric acid (GABA) resulted in a biphasic effect of the temperature selection, whereas microinjection with muscimol, an agonist of GABAA receptor, had no effect on temperature selection. Both agonist and antagonist of glutamate (Glu), N‐methyl‐D‐aspartate (NMDA), and MK‐801 (1.0×10−6 M), a noncompetitive blocker of NMDA receptor, significantly decreased the preferred temperature. These results indicate that the hypothalamic 5‐HT, GABA, and Glu systems play a role in the temperature selection of prespawning female tilapia. J. Exp. Zool. 293:443–449, 2002. © 2002 Wiley‐Liss, Inc.
Skin flaps inhibit both the current of injury at the amputation surface and regeneration of that limb in newts
Authors: Altizer Alicia M. , Stewart Sarah G. , Albertson Brian K. , Borgens Richard B. 
Published: June 2004

AbstractFor over two decades, we have been investigating a strong (ca. 20–100 µA/cm2), outwardly directed electric current driven through the limb stump for the first few days following amputation in regenerating salamanders. This current is driven through the stump in a proximal/distal direction by the amiloride‐sensitive transcutaneous voltage of the intact skin of the stump. Limb regeneration can be manipulated by several techniques that manipulate this physiology, demonstrating that the ionic current is necessary, but not sufficient, for normal regeneration of the amphibian limb. Here, we demonstrate that a full thickness graft of skin covering the forelimb stump of newts strikingly inhibits the regeneration of the limb, and that this procedure is also highly correlated to a suppression of peak outwardly directed stump currents in those animals that fail to regenerate. J. Exp. Zool. 293:467–477, 2002. © 2002 Wiley‐Liss, Inc.
Effects of posture on the respiratory mechanics of the chick embryo
Authors: Menna Tara M. , Mortola Jacopo P. 
Published: June 2004

AbstractIn the chicken embryo, pulmonary ventilation and pulmonary gas exchange begin approximately one day before the completion of hatching. We asked to what extent the posture inside the egg, and the presence of the eggshell and membranes, may alter the mechanical behaviour of the respiratory system. The passive mechanical properties of the respiratory system were studied in chicken embryos during the internal pipping phase (rupture of the air cell) or the external pipping phase (hole in the eggshell). Tracheal pressure and changes in lung volume were recorded during mechanical ventilation, first, with the embryo curled up inside the egg, then again after exteriorization from the eggshell. In the internal pippers, respiratory system compliance increased and expiratory resistance decreased after exteriorization, whereas the mean inspiratory impedance did not change. In the external pippers, exteriorization had no significant effects on respiratory compliance, resistance, or impedance, and the values were similar to those of newly hatched chicks. We conclude that, in the chicken embryo, at a time when pulmonary ventilation becomes an important mechanism for gas exchange, the curled up posture inside the egg does not provide any significant mechanical constraint to breathing. J. Exp. Zool. 293:450–455, 2002. © 2002 Wiley‐Liss, Inc.
Mollusc larval shell formation: amorphous calcium carbonate is a precursor phase for aragonite
Authors: Weiss Ingrid Maria , Tuross Noreen , Addadi Lia , Weiner Steve 
Published: June 2004

AbstractThe larval shells of the marine bivalves Mercenaria mercenaria and Crassostrea gigas are investigated by polarized light microscopy, infrared spectroscopy, Raman imaging spectroscopy, and scanning electron microscopy. Both species contain similar shell ultrastructures. We show that larval shells contain amorphous calcium carbonate (ACC), in addition to aragonite. The aragonite is much less crystalline than nonbiogenic aragonite. We further show that the initially deposited mineral phase is predominantly ACC that subsequently partially transforms into aragonite. The postset juvenile shell, as well as the adult shell of Mercenaria also contains aragonite that is less crystalline than nonbiogenic aragonite. We conclude that ACC fulfills an important function in mollusc larval shell formation. It is conceivable that ACC may also be involved in adult shell formation. J. Exp. Zool. 293:478–491, 2002. © 2002 Wiley‐Liss, Inc.
Characterization of aromatase activity in the sea bass: effects of temperature and different catalytic properties of brain and ovarian homogenates and microsomes
Authors: González Alicia , Piferrer Francesc 
Published: June 2004

AbstractTwo aromatase genes have been discovered in the brain and ovary of some teleosts. However, data on native aromatase enzyme kinetics and thus actual catalytic activity are scarce in fish, impeding comparison of aromatase activity (AA) from different organs within and between species. In the present study, the tritiated water assay was optimized and validated to measure AA in the sea bass using 1β‐[3H]‐androstenedione as a substrate in crude homogenates and microsomes. Optimized assay variables included pH, temperature, buffer strength, incubation time, amount of fresh tissue, substrate, and cofactor concentration. Specificity of the assay was verified by using known inhibitors, inappropriate substrates, and heat‐inactivation. Subcellular fractionation revealed ten‐fold more activity in the microsomal over the cytosolic fraction. The assay was also validated by comparing results from the direct product isolation method. The validated assay described allows measurement of AA to levels as low as < 10 fmol/mg protein/hr. Sex differentiation is temperature‐dependent in the sea bass. It was found that in the physiological range of temperatures where the sea bass can live, 10–30°C, AA is highly dependent on temperature in a linear fashion (brain: r2 = 0.92; P<0.001; ovary: r2 = 0.94; P<0.001). When AA levels from brain and ovarian homogenates obtained from the same fish during the spawning season were compared, the respective Michaelis‐Menten constant (Km) values were 7.3 nM vs. 4.6 nM, with no significant differences detected between the two tissues. Thus, sea bass aromatase has a very high affinity for androstenedione, similar to what has been found in goldfish, but much higher than other piscine or mammalian aromatases (30–435 nM). In contrast, the brain maximum reaction rate (Vmax 7.8 pmol/mg protein/hr) was four‐fold higher (P<0.001) than the ovarian Vmax (2.1 pmol/mg protein/hr). Consistent results were found using purified microsomes. Although this is the first time that the kinetic parameters are reported for a native piscine aromatase in two different tissues within the same fish, it remains to be determined whether this is a reflection of two distinct isoforms in this particular species. J. Exp. Zool. 293:500–510, 2002. © 2002 Wiley‐Liss, Inc.
Induction of parturition in snow skinks: can low temperatures inhibit the actions of AVT?
Authors: Girling Jane E. , Jones Susan M. , Swain Roy 
Published: June 2004

AbstractThe influence of environmental factors on the timing of parturition has not been investigated in viviparous squamates. We investigated the interaction between temperature and parturition in two viviparous skink species, the southern snow skink (Niveoscincus microlepidotus) and the metallic skink (N. metallicus). In these species, the timing of parturition is separated from the completion of embryonic development; the delay is attributed to their cool and variable habitats. We examined whether the neurohypophyseal hormone arginine vasotocin (AVT) stimulated parturition in southern snow skinks with late stage embryos in autumn (≈6–7 months prior to parturition) and in metallic skinks with late stage embryos in summer (≈2–3 weeks prior to parturition). The experiments were conducted at a range of environmentally relevant temperatures (6°C, 15°C, 22°C, and 28°C). AVT induced parturition in both species at all temperatures; time until birth, however, occurred more quickly at warmer temperatures (22°C and 28°C), whereas cooler temperatures delayed parturition. We hypothesize that if cool temperatures are preventing parturition, then temperature must act at some level within the brain to prevent or slow the secretion of AVT. Future experiments will need to determine how temperature influences AVT production. Further research is also required to determine how the timing of parturition is influenced by interactions between temperature, photoperiod, and seasonal hormone patterns. J. Exp. Zool. 293:525–531, 2002. © 2002 Wiley‐Liss, Inc.
A biographical note on Max Friedrich (1856–1887), Wundt's first PhD student in experimental psychology
Authors: Domanski Cezary W. 
Published: June 2004

AbstractThis article unveils some previously unknown facts about the short life of Max Friedrich (1856–1887), the author in 1881 of the first PhD dissertation on experimental psychology, written under the supervision of Wilhelm Wundt: “On the Duration of Apperception for Simple and Complex Visual Stimuli.” The article describes Friedrich's family background and life, professional career as a teacher, and works in psychology and mathematics. © 2004 Wiley Periodicals, Inc.
Historiography taking issue: Analyzing an experiment with heroin abusers
Authors: Dehue Trudy 
Published: June 2004

AbstractThis article discusses the predicament of historians becoming part of the history they are investigating and illustrates the issue in a particular case. The case is that of the randomized controlled trial (RCT)—more specifically, its use for testing the effects of providing heroin to severe heroin abusers. I counter the established view of the RCT as a matter of timeless logic and argue that this research design was developed in the context of administrative knowledge making under twentieth‐century economic liberalism of which it epitomizes some central values. I also argue that the applicability of the RCT depends on the degree to which its advocates can define the issue to be studied according to its inherent values. Next, I demonstrate how advocates of an RCT with heroin provision in the Netherlands steered the political discussion on heroin provision and how the values of economic liberalism also shaped the results of the Dutch maintenance experiment. In addition, I relate how my analysis of this experiment became part of political debates in the Netherlands. Contrary to my intentions, adversaries of heroin maintenance used my critique on the heroin RCT as an argument against heroin maintenance. Such risks are inherent to historiography and sociology of science aiming at practical relevance while challenging treasured scientific beliefs. I conclude that it still seems better to expose arguments on unjustified certainties than to suppress them for strategic reasons. © 2004 Wiley Periodicals, Inc.
The establishment of the department of psychiatry in the Mount Sinai Hospital: A conflict between neurology and psychiatry
Authors: Stein Marvin 
Published: June 2004

AbstractA conflict between neurology and psychiatry and controversies about psychoanalysis played an important role in the establishment of psychiatry in the general hospital. This article reviews the impact of this conflict on the establishment of an independent Department of Psychiatry in the Mount Sinai Hospital in New York during the first half of the twentieth century. A unique opportunity is provided to consider the relationships and personalities of the individuals involved, as well as economic, social, and scientific factors, including the introduction of psychoanalysis as a major psychiatric treatment. © 2004 Wiley Periodicals, Inc.
Mass spectrometry and partial least‐squares regression: a tool for identification of wheat variety and end‐use quality
Authors: Sørensen Helle A. , Petersen Marianne K. , Jacobsen Susanne , Søndergaard Ib 
Published: June 2004

AbstractRapid methods for the identification of wheat varieties and their end‐use quality have been developed. The methods combine the analysis of wheat protein extracts by mass spectrometry with partial least‐squares regression in order to predict the variety or end‐use quality of unknown wheat samples. The whole process takes ∼30 min. Extracts of alcohol‐soluble storage proteins (gliadins) from wheat were analysed by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry. Partial least‐squares regression was subsequently applied using these mass spectra for making models that could predict the wheat variety or end‐use quality. Previously, an artificial neural network was used to identify wheat varieties based on their protein mass spectra profiles. The present study showed that partial least‐squares regression is at least as useful as neural networks for this identification. Furthermore, it was demonstrated that partial least‐squares regression could be used to predict wheat end‐use quality, which has not been possible using neural networks. Copyright © 2004 John Wiley & Sons, Ltd.
Internal energy build‐up in matrix‐assisted laser desorption/ionization
Authors: Gabelica Valérie , Schulz Eric , Karas Michael 
Published: June 2004

AbstractThis paper reports detailed studies on the internal energy of ions formed in matrix‐assisted laser desorption/ionization (MALDI) using delayed extraction MALDI‐time‐of‐flight (TOF) and atmospheric pressure (AP) MALDI mass spectrometric (MS) methods. We use benzylpyridinium cations as internal energy probes. Our study reveals three distinct contributions to internal energy build‐up in vacuum‐MALDI (classical MALDI‐TOF), each having different effects on ion fragmentation. Some fragments are formed before ion extraction (i.e. no more than 100 ns after the laser impact), and they are therefore well resolved and recorded as sharp signals in the MALDI‐TOFMS scan. This prompt fragmentation can have two origins: (i) in‐plume thermal activation, presumably always present, and (ii) in‐plume chemical activation, in the course of reactions with hydrogen radicals. In addition to early internal energy build‐up associated with these well‐resolved promptly formed fragments, a broad peak slightly offset to higher masses could be detected corresponding to fragments formed after the extraction has started. This second signal corresponds to a third source of internal energy in MALDI ions, (iii) the extraction‐induced collisional activation of the ions with the neutral components of the plume. These three contributions are difficult to quantify in vacuum‐MALDI, because of the combined influence of several parameters (nature of the matrix, spot‐to‐spot variability, total laser exposure, delay time, acceleration voltage) on extraction‐induced fragmentation. AP‐MALDI, on the other hand, has two advantages for comparative studies of analyte fragmentation. First, extraction‐induced fragmentation is absent, and only the contributions of early plume activation remain. Second, the reproducibility is far better than in vacuum‐MALDI. AP‐MALDI is therefore expected to shed new light on the early steps of the MALDI process. Copyright © 2004 John Wiley & Sons, Ltd.