bluuebunny/crossref_metadata_2025 huggingface dataset:
PAR3 is essential for cyst-mediated epicardial development by establishing apical cortical domains
Authors: Hirose Tomonori , Karasawa Mika , Sugitani Yoshinobu , Fujisawa Masayoshi , Akimoto Kazunori , Ohno Shigeo , Noda Tetsuo
Published: March 2006

Epithelial cysts are one of the fundamental architectures for mammalian organogenesis. Although in vitro studies using cultured epithelial cells have revealed proteins required for cyst formation, the mechanisms that orchestrate the functions of these proteins in vivo remain to be clarified. We show that the targeted disruption of the mouse Par3 gene results in midgestational embryonic lethality with defective epicardial development. The epicardium is mainly derived from epicardial cysts and essential for cardiomyocyte proliferation during cardiac morphogenesis. PAR3-deficient epicardial progenitor (EPP) cells do not form cell cysts and show defects in the establishment of apical cortical domains, but not in basolateral domains. In PAR3-deficient EPP cells, the localizations of aPKC, PAR6β and ezrin to the apical cortical domains are disturbed. By contrast, ZO1 andα4/β1 integrins normally localize to cell-cell junctions and basal domains, respectively. Our observations indicate that EPP cell cyst formation requires PAR3 to interpret the polarity cues from cell-cell and cell-extracellular matrix interactions so that each EPP cell establishes apical cortical domains. These results also provide a clear example of the proper organization of epithelial tissues through the regulation of individual cell polarity.
Essential and opposing roles of zebrafish β-catenins in the formation of dorsal axial structures and neurectoderm
Authors: Bellipanni Gianfranco , Varga Máté , Maegawa Shingo , Imai Yoshiyuki , Kelly Christina , Myers Andrea Pomrehn , Chu Felicia , Talbot William S. , Weinberg Eric S.
Published: March 2006

In Xenopus, Wnt signals and their transcriptional effectorβ-catenin are required for the development of dorsal axial structures. In zebrafish, previous loss-of-function studies have not identified an essential role for β-catenin in dorsal axis formation, but the maternal-effect mutation ichabod disrupts β-catenin accumulation in dorsal nuclei and leads to a reduction of dorsoanterior derivatives. We have identified and characterized a second zebrafish β-catenin gene,β-catenin-2, located on a different linkage group from the previously studied β-catenin-1, but situated close to the ichabod mutation on LG19. Although the ichabod mutation does not functionally alter the β-catenin-2 reading frame, the level of maternal β-catenin-2, but not β-catenin-1,transcript is substantially lower in ichabod, compared with wild-type, embryos. Reduction of β-catenin-2 function in wild-type embryos by injection of morpholino antisense oligonucleotides (MOs)specific for this gene (MO2) results in the same ventralized phenotypes as seen in ichabod embryos, and administration of MO2 to ichabod embryos increases the extent of ventralization. MOs directed against β-catenin-1 (MO1), by contrast, had no ventralizing effect on wild-type embryos. β-catenin-2 is thus specifically required for organizer formation and this function is apparently required maternally, because the ichabod mutation causes a reduction in maternal transcription of the gene and a reduced level of β-catenin-2 protein in the early embryo. A redundant role of β-catenins in suppressing formation of neurectoderm is revealed when both β-catenin genes are inhibited. Using a combination of MO1 and MO2 in wild-type embryos,or by injecting solely MO1 in ichabod embryos, we obtain expression of a wide spectrum of neural markers in apparently appropriate anteroposterior pattern. We propose that the early, dorsal-promoting function ofβ-catenin-2 is essential to counteract a later, dorsal- and neurectoderm-repressing function that is shared by both β-catenin genes.
Cooperative action of Sox9, Snail2 and PKA signaling in early neural crest development
Authors: Sakai Daisuke , Suzuki Takashi , Osumi Noriko , Wakamatsu Yoshio
Published: March 2006

In neural crest formation, transcription factors, such as group E Sox and Snail1/Snail2 (Slug) regulate subsequent epithelial-mesenchymal transition (EMT) and migration. In particular, Sox9 has a strong effect on neural crest formation, EMT and differentiation of crest-derived cartilages in the cranium. It remains unclear, however, how Sox9 functions in these events, and how Sox9 activity is regulated. In this study, our gain-of-function and loss-of-function experiments reveal that Sox9 is essential for BMP signal-mediated induction of Snail2 and subsequent EMT in avian neural crest. We also show that Snail2 activates the Snail2 promoter, although Snail family proteins have been known as a repressor. Consistently, Sox9 directly activates the Snail2 promoter in synergy with, and through a direct binding to,Snail2. Finally, functions of these transcription factors in neural crest cells are enhanced by PKA signaling.
A tyrosine-rich domain within homeodomain transcription factor Nkx2-5 is an essential element in the early cardiac transcriptional regulatory machinery
Authors: Elliott David A. , Solloway Mark J. , Wise Natalie , Biben Christine , Costa Mauro W. , Furtado Milena B. , Lange Martin , Dunwoodie Sally , Harvey Richard P.
Published: March 2006

Homeodomain factor Nkx2-5 is a central component of the transcription factor network that guides cardiac development; in humans, mutations in NKX2.5 lead to congenital heart disease (CHD). We have genetically defined a novel conserved tyrosine-rich domain (YRD) within Nkx2-5 that has co-evolved with its homeodomain. Mutation of the YRD did not affect DNA binding and only slightly diminished transcriptional activity of Nkx2-5 in a context-specific manner in vitro. However, the YRD was absolutely essential for the function of Nkx2-5 in cardiogenesis during ES cell differentiation and in the developing embryo. Furthermore, heterozygous mutation of all nine tyrosines to alanine created an allele with a strong dominant-negative-like activity in vivo: ES cell↔embryo chimaeras bearing the heterozygous mutation died before term with cardiac malformations similar to the more severe anomalies seen in NKX2.5 mutant families. These studies suggest a functional interdependence between the NK2 class homeodomain and YRD in cardiac development and evolution, and establish a new model for analysis of Nkx2-5 function in CHD.
The developing lamprey ear closely resembles the zebrafish otic vesicle:otx1expression can account for all major patterning differences
Authors: Hammond Katherine L. , Whitfield Tanya T.
Published: March 2006

The inner ear of adult agnathan vertebrates is relatively symmetric about the anteroposterior axis, with only two semicircular canals and a single sensory macula. This contrasts with the highly asymmetric gnathostome arrangement of three canals and several separate maculae. Symmetric ears can be obtained experimentally in gnathostomes in several ways, including by manipulation of zebrafish Hedgehog signalling, and it has been suggested that these phenotypes might represent an atavistic condition. We have found,however, that the symmetry of the adult lamprey inner ear is not reflected in its early development; the lamprey otic vesicle is highly asymmetric about the anteroposterior axis, both morphologically and molecularly, and bears a striking resemblance to the zebrafish otic vesicle. The single sensory macula originates as two foci of hair cells, and later shows regions of homology to the zebrafish utricular and saccular maculae. It is likely, therefore, that the last common ancestor of lampreys and gnathostomes already had well-defined otic anteroposterior asymmetries. Both lamprey and zebrafish otic vesicles express a target of Hedgehog signalling, patched, indicating that both are responsive to Hedgehog signalling. One significant distinction between agnathans and gnathostomes, however, is the acquisition of otic Otx1 expression in the gnathostome lineage. We show that Otx1 knockdown in zebrafish, as in Otx1-/- mice, gives rise to lamprey-like inner ears. The role of Otx1 in the gnathostome ear is therefore highly conserved; otic Otx1 expression is likely to account not only for the gain of a third semicircular canal and crista in gnathostomes, but also for the separation of the zones of the single macula into distinct regions.
Cessation of Fgf10 signaling, resulting in a defective dental epithelial stem cell compartment, leads to the transition from crown to root formation
Authors: Yokohama-Tamaki Tamaki , Ohshima Hayato , Fujiwara Naoki , Takada Yunosuke , Ichimori Yasuo , Wakisaka Satoshi , Ohuchi Hideyo , Harada Hidemitsu
Published: March 2006

Mouse, rat and human molars begin to form root after the completion of crown formation. In these teeth, fibroblast growth factor (Fgf) 10 disappears in the transitional stage from crown formation to root. By contrast, rodent incisors and vole molars demonstrate continuous growth, owing to the formation and maintenance of a stem cell compartment by the constant expression of Fgf10. To clarify the relationship between root formation and disappearance of Fgf10, we carried out two experiments for the loss and gain of Fgf10 function. First, we examined postnatal growth in the incisors of Fgf10-deficient mice, which have the defect of a dental epithelial stem cell compartment referred to as `apical bud', after implantation under the kidney capsule. The growth at the labial side in the mutant mice mimics the development of limited-growth teeth. 5′-Bromo-2′-deoxyuridine (BrdU) labeling and cytokeratin (CK) 14 and Notch2 immunostaining suggested that the inhibition of inner enamel epithelium growth and the more-active proliferation of the outer enamel epithelium and/or stellate reticulum result in Hertwig's epithelial root sheath formation. Second, we examined the effects of Fgf10overexpression in the transitional stage of molar germs, which led to the formation of apical bud involving in the inhibition of HERS formation. Taken together, these results suggest that the disappearance of Fgf10 signaling leads to the transition from crown to root formation, owing to the loss of a dental epithelial stem cell compartment.
The role of single spiking spherical neurons in a fast sensory pathway
Authors: Nogueira Javier , Castelló María E. , Caputi Angel Ariel
Published: March 2006

One difficulty in understanding the brain is that of linking the structure of the neurons with their computational roles in neural circuits. In this paper we address this subject in a relative simple system, the fast electrosensory pathway of an electric fish, where sensory images are coded by the relative latency of a volley of single spikes. The main input to this path is a stream of discrete electric images resulting from the modulation of a self-generated carrier by the environment. At the second order cell level, a window of low responsiveness, reducing potential interference from other stimuli, follows activation of the path.

In the present study, we further characterize the input–output relationship at the second order neurons by recording field potentials, and ascertain its cellular basis using in vitro whole cell patch recordings. The field potentials from freely behaving, socially interacting fish were obtained from chronically implanted fish restrained in a mesh pen. In addition, at the end of some experiments the fish was curarized and the fast electrosensory path responses to artificial stimuli were further explored. These in vivo approaches showed that larger stimuli cause larger and longer windows of low responsiveness. The simple spherical geometry of the second order cells allowed us to unveil the membrane mechanisms underlying this phenomenon in vitro. These spherical cells respond with a single spike at the onset of current steps of any amplitude and duration, showing inward and outward rectification, and a long refractory period. We postulate that a low-threshold K+ conductance generates the outward rectification. The most parsimonious interpretation of our data indicates that slow deactivation of this conductance causes the long refractory period. These non-linear properties of the membrane explain the single spiking profile of spherical cells and the low-responsiveness window observed in vivo. Since the electric organ discharges are emitted at intervals slightly longer than the duration of the low-responsiveness window,we propose that the described cellular mechanisms allow fish streaming self-generated images.
Temperature dependence of cardiac performance in the lobsterHomarus americanus
Authors: Worden Mary Kate , Clark Christine M. , Conaway Mark , Qadri Syed Aman
Published: March 2006

The lobster Homarus americanus inhabits ocean waters that vary in temperature over a 25°C range, depending on the season and water depth. To investigate whether the lobster heart functions effectively over a wide range of temperatures we examine the temperature dependence of cardiac performance of isolated lobster hearts in vitro. In addition, we examined whether modulation of the heart by serotonin depends on temperature. The strength of the heartbeat strongly depends on temperature, as isolated hearts are warmed from 2 to 22°C the contraction amplitude decreases by greater than 60%. The rates of contraction and relaxation of the heart are most strongly temperature dependent in the range from 2 to 4°C but become temperature independent at warmer temperatures. Heart rates increase as a function of temperature both in isolated hearts and in intact animals, however hearts in intact animals beat faster in the temperature range of 12–20°C. Interestingly, acute Q10 values for heart rate are similar in vivo and in vitro over most of the temperature range, suggesting that temperature dependence of heart rate arises mainly from the temperature effects on the cardiac ganglion. In contrast to earlier reports suggesting that the strength and the frequency of the lobster heartbeat are positively correlated, we observe no consistent relationship between these parameters as they change as a function of temperature. Stroke volume decreases as a function of temperature. However, the opposing temperature-dependent increase in heart rate partially compensates to produce a relationship between cardiac output and temperature in which cardiac output is maximal at 10°C and significantly decreases above 20°C. Serotonin potentiates contraction amplitude and heart rate in a temperature-independent manner. Overall, our results show that although the parameters underlying cardiac performance show different patterns of temperature dependence, cardiac output remains relatively constant over most of the wide range of environmental temperatures the lobster inhabits in the wild.
Glycerol production in rainbow smelt (Osmerus mordax) may be triggered by low temperature alone and is associated with the activation of glycerol-3-phosphate dehydrogenase and glycerol-3-phosphatase
Authors: Driedzic William R. , Clow Kathy A. , Short Connie E. , Ewart K. Vanya
Published: March 2006

Rainbow smelt (Osmerus mordax) accumulate high levels of glycerol in winter that serves as an antifreeze. Fish were subjected to controlled decreases in water temperature and levels of plasma glycerol, liver metabolites and liver enzymes were determined in order to identify control mechanisms for the initiation of glycerol synthesis. In two separate experiments, decreases in temperature from 8°C to 0°C over a period of 10–11 days resulted in increases in plasma glycerol from levels of less than 4 mmol l–1 to approximate mean levels of 40 (first experiment) and 150 mmol l–1 (second experiment). In a third experiment, decreases in temperature to –1°C resulted in plasma glycerol levels approaching 500 mmol l–1. The accumulation of glycerol could be driven in either December or March, thus eliminating decreasing photoperiod as a necessary cue for glycerol accumulation. Glycerol accumulation in plasma was associated with changes in metabolites in liver leading to increases in the mass action ratio across the reactions catalyzed by glycerol-3-phosphate dehydrogenase (GPDH) and glycerol-3-phosphatase(G3Pase). The maximal, in vitro activity of GPDH, increased twofold in association with a sharp increase in plasma glycerol level. The metabolite levels and enzyme activities provide complementary evidence that GPDH is a regulatory site in the low temperature triggered synthesis of glycerol. Indirect evidence, based on calculated rates of in vivo glycerol production by liver, suggests that G3Pase is a potential rate-limiting step. As well, transient increases in glyceraldehyde-3-phosphate dehydrogenase and alanine aminotransferase suggest that these sites are components of a suite of responses, in rainbow smelt liver, induced by low temperature.
Carotenoid availability in diet and phenotype of blue and great tit nestlings
Authors: Biard Clotilde , Surai Peter F. , Møller Anders P.
Published: March 2006

Carotenoids are biologically active pigments of crucial importance for the development of avian embryos and nestlings. Thus parental ability to provide nestlings with a carotenoid-rich diet may enhance offspring fitness. However,very little is known about the possible effects of carotenoid availability in the diet on growing nestlings in natural populations. We experimentally manipulated dietary intake of carotenoids by nestlings of two closely related passerine species, the great tit Parus major and the blue tit Parus caeruleus, and measured nestling antioxidants, body condition,immunity and plumage colour. There was no detectable increase in plasma carotenoids after treatment in carotenoid-fed nestlings of either species despite regular supply of dietary carotenoids. However, in carotenoid-fed blue tit nestlings, plasma vitamin E concentration increased with plasma carotenoid concentration, while that was not the case for control nestlings. In both species, there was no significant effect of carotenoid supply on immune function. Carotenoid supplementation enhanced yellow feather colour in great tit nestlings only. In both species a strong effect of carotenoid supply was found on body condition with an increase in body mass for small carotenoid-fed nestlings compared to similarly sized control nestlings. Dietary availability of carotenoids may thus have important fitness consequences for tits. We hypothesise that the difference in effect of dietary carotenoids on the two species is due to relatively larger clutch size and higher growth rates of blue tits compared to great tits, leading to blue tit nestlings being more in need of carotenoids for antioxidant function than great tit nestlings.
Hydration of rainbow trout oocyte during meiotic maturation andin vitroregulation by 17,20β-dihydroxy-4-pregnen-3-one and cortisol
Authors: Milla Sylvain , Jalabert Bernard , Rime Helene , Prunet Patrick , Bobe Julien
Published: March 2006

Although oocytes of many teleost fish, especially marine species, are subjected to a hydration process during meiotic maturation, which leads to an important volume increase, no noticeable hydration of the preovulatory oocyte has ever been reported in rainbow trout (Oncorhynchus mykiss). In the present study, oocyte water content and dry mass were monitored using consecutive samples taken in vivo from the same female rainbow trout,from 4–5 days prior to ovulation to up to 7 days post-ovulation. In addition, yolk protein electrophoretic patterns were compared between oocytes sampled prior to germinal vesicle breakdown (GVBD) and unfertilized eggs. Furthermore, the effect of the maturation-inducing steroid(17,20β-dihydroxy-4-pregnen-3-one, 17,20β-P), cortisol and 11-deoxycorticosterone (DOC) on oocyte dry and wet masses, as well as GVBD occurrence was assessed in vitro. Finally, mRNA expression profiles of glucocorticoid and mineralocorticoid receptors as well as 11β-hydroxysteroid dehydrogenase (11β-HSD) were monitored in the periovulatory ovary by real-time PCR. Both in vivo and in vitro data showed, for the first time in rainbow trout, that a significant oocyte hydration occurs during oocyte maturation. In addition, an intra-oocyte dry matter increase was reported in vivo during the periovulatory period. However, yolk protein migration patterns were similar in preGVBD oocytes and unfertilized eggs, suggesting that no or little yolk proteolysis occurs during oocyte maturation. We also showed that oocyte hydration can be induced in vitro by 17,20β-P and cortisol but not by DOC. In contrast, GVBD was only observed after 17,20β-P stimulation. Finally, real-time PCR analysis showed an up-regulation of 11β-HSD and glucocorticoid receptor 2 transcripts in the ovary at the time of oocyte maturation. Together, these results suggest that cortisol could participate in the control of oocyte hydration and possibly in other periovulatory ovarian functions.
Seismic signal production in a wolf spider: parallelversusserial multi-component signals
Authors: Elias Damian O. , Lee Norman , Hebets Eileen A. , Mason Andrew C.
Published: March 2006

Animal signals can consist of multiple parts within or across sensory modalities (multi-component signals or multimodal signals). While recent work has focused on multimodal signals, the production, processing and evolution of multi-component signals has received considerably less attention. Here, using synchronous high-speed video and laser vibrometer recordings followed by experimental manipulations of putative sound-producing structures, we explored the mechanisms of seismic signal production in the courtship display of Schizocosa stridulans Stratton. Two types of seismic courtship signals were observed: `rev' and `idle' signals. Revs consist of a high-frequency component produced by flexions of the male pedipalp(stridulation) simultaneous with a low-frequency component produced by movements of the abdomen (tremulation). This multi-component signal is produced by independent structures and represents a parallel multi-component display. By contrast, idle displays consist of a high-intensity component produced by drumming of the forelegs on the substrate (percussion) followed by a high-frequency component produced by flexions of the male pedipalp(stridulation). While the components of the idle display are also produced by independent structures, the leg drumming and palp flexions occur serially and do not overlap in time. We discuss the selective pressures that may drive the evolution of multiple sound-producing structures as well as the selective pressures that drive the evolution of parallel versus serial multi-component signals.
Chronic hypercapnia modulates respiratory-related central pH/CO2 chemoreception in an amphibian,Bufo marinus
Authors: Gheshmy Afshan , Vukelich Robert , Noronha Angelo , Reid Stephen G.
Published: March 2006

Anuran amphibians have multiple populations of pH/CO2-sensitive respiratory-related chemoreceptors. This study examined in cane toads(Bufo marinus) whether chronic hypercapnia (CHC) altered the pH/CO2 sensitivity of central respiratory-related chemoreceptors in vitro and whether CHC altered the acute hypercapnic ventilatory response (HCVR; 5% CO2) in vivo. Toads were exposed to CHC(3.5% CO2) for 9 days. In vitro brainstem–spinal cord preparations were used to examine central respiratory-related pH/CO2 chemosensitivity. CHC augmented in vitro fictive breathing as the pH of the superfusate was lowered from 8.2 to 7.4. Midbrain transection in vitro (at a level known to reduce the clustering of breaths) did not alter this augmentation. In vivo, CHC did not alter the acute HCVR but midbrain transection changed the breathing pattern and increased the overall level of ventilation. CHC did not alter the effect of olfactory CO2 chemoreceptor denervation on the acute HCVR in vivo but did alter the response when returned to normal air. The results indicate that CHC increases the response of central pH/CO2chemoreceptors to changes in cerebrospinal fluid pH in vitro yet this increase is not manifest as an increase in the HCVR in vivo.
How much stress do researchers inflict on their study animals? A case study using a scincid lizard, Eulamprus heatwolei
Authors: Langkilde Tracy , Shine Richard
Published: March 2006

Research on live vertebrates is regulated by ethics committees, who prohibit `excessively stressful' procedures. That judgment is based on intuition – a notoriously unreliable criterion when dealing with animals phylogenetically distant from humans. To objectively evaluate the stress imposed by research practices, we measured plasma corticosterone levels in lizards (Eulamprus heatwolei Wells & Wellington, Scincidae). Some procedures (handling and measuring, toe-clipping for identification, exposure to predator scent) did not induce significant increases in corticosterone levels, suggesting that these stimuli generated relatively little stress. However, other stimuli (testing locomotor speed, microchip implantation, blood sampling, an unfamiliar enclosure, tail autotomy, exposure to a heterospecific lizard) were more stressful, with corticosterone levels increasing only transiently in some treatments (<2 h for tail autotomy), but persisting much longer in others (14 days for microchip implantation). Overall, our data suggest that the levels of stress induced by routine laboratory procedures are no greater than those often experienced by lizards in nature; but that intuition provides a poor basis for evaluating the levels of stress induced by research. For example, toe-clipping is often criticized and sometimes banned;but our data suggest that this method is actually less stressful than the technique frequently recommended to replace it on ethical grounds (microchip implantation). Toe-clipping also was less stressful than superficially trivial manipulations such as housing the animal in an unfamiliar enclosure. More generally, we urge researchers to seek objective information on the effects of their activities on research subjects, rather than relying upon subjectivity and anthropomorphism in making these evaluations.
Differential parental nutrient allocation in two congeneric pipefish species (Syngnathidae:Syngnathusspp.)
Authors: Ripley Jennifer L. , Foran Christy M.
Published: March 2006

Male seahorses and pipefishes of the family Syngnathidae are heralded for their unique brood pouch structures for incubating embryos. There are three general types of brood pouch with increasing complexity: simple ventral gluing, two pouch flaps and a completely sealed sac. The diversity of functional roles within a type in providing nutrition, aeration and protection to offspring is unknown. Here we reveal significant differences in parental nutrient allocation to embryos for two closely related, sympatric pipefishes with similar brood pouch structure. We document differences in embryo attachment, depletion of pouch fluid nutrients over development and egg nutrient partitioning between Syngnathus floridae and Syngnathus fuscus. In S. fuscus, females produce nutritionally poor eggs and the males implant developing embryos in the brood pouch adjacent to blood vessels. A female-biased breeding population was observed, supporting the hypothesis that the cost of male parental care is high in this species. The loose connection between eggs and brood pouch tissues and the appearance of undeveloped eggs and lipid droplets in the pouch of S. floridae males suggest this species utilizes nutrient-rich eggs produced by females as nurse eggs to supplement embryonic development. A balanced sex-ratio for S. floridae further supports more equal parental contribution. This comparison provides evidence of a decline in female gametic investment and reveals the rapid diversification of syngnathid brood pouch function. Our results indicate gross classification of brooding structures into one of the three general pouch types does not predict the energetic investment of males in parental care. But rather, physiological characterization of the relative investment by each sex to offspring is essential to understanding the functional significance of the brood pouch.
Metabolic and blood gas dependence on digestive state in the Savannah monitor lizardVaranus exanthematicus: an assessment of the alkaline tide
Authors: Hartzler L. K. , Munns S. L. , Bennett A. F. , Hicks J. W.
Published: March 2006

A large alkaline tide (up to 20 mmol l–1 increase in bicarbonate concentration [HCO3–] with an accompanied increase in blood pH) has previously been reported for some carnivorous reptiles within 24 h after ingesting a large meal. This phenomenon has been attributed to the secretion of large amounts of H+ ions into the stomach, which is required for digestion of large prey items. To test the generality of this phenomenon in carnivorous reptiles, this study quantified the metabolic and acid–base status of the Savannah monitor lizard, Varanus exanthematicus, during digestion at 35°C. Following a meal of approximately 10% of body mass, V̇O2 and V̇CO2 were measured continuously and arterial pH, blood gases and strong ions were measured every 8 h for 5 days. During peak digestion (24 h post feeding), V̇O2 and V̇CO2 increased to approximately threefold fasting values(V̇O2, 0.95–2.57 ml min–1 kg–1; V̇CO2 0.53–1.63 ml min–1 kg–1) while respiratory exchange ratio(R) remained constant (0.62–0.73). During digestion, arterial PCO2 increased (from 4.6 kPa to 5.8 kPa), and[HCO3–] also increased (from 24.1 mmol l–1 to 40.3 mmol l–1). In contrast to early studies on crocodilians, arterial pH in V. exanthematicus remained relatively stable during digestion (7.43–7.56). Strong ions contributed little to the acid–base compensation during the alkalosis. Collectively the data indicate that the metabolic alkalosis associated with H+secretion (as indicated by increased plasma bicarbonate) is partially compensated by a respiratory acidosis.
Developmentally determined attenuation in circadian rhythms links chronobiology to social organization in bees
Authors: Yerushalmi Shai , Bodenhaimer Shalev , Bloch Guy
Published: March 2006

We investigated labor-related plasticity in the circadian clock of the bumblebee Bombus terrestris. Bumblebee workers vary enormously in body size, and we found that size, division of labor, and diurnal rhythms in activity are correlated in B. terrestris colonies. Large workers typically perform foraging activities with strong diurnal rhythms and low activity at night, whereas small bees typically care for (nurse) brood around the clock with weak or no diurnal rhythms. Under constant laboratory conditions, circadian rhythms in locomotor activity were weaker, less stable,and developed at a later age in small (nurse-size) bees compared to their larger (forager-size) sisters. Under a light:dark illumination regime, many small bees, particularly at a young age, were active during the dark phase,fewer small bees developed rhythms, and they did so later compared to large bees. Taken together these findings reveal naturally occurring attenuation or suppression in the circadian clock of small bees that is determined during pre-adult development. This deficiency in clock function, however, does not result in pathology but rather appears to be functionally significant, because it is associated with around-the-clock brood care activity and therefore apparently improves divisions of labor and colony efficiency. This in turn suggests that variation in social biology influences traits of the circadian clock.
α-Fluorination of Sulfoxides Bearing α-Hydrogens by Molecular Fluorine. A Novel Method for the Synthesis of α-Fluorosulfones
Authors: Chiba Jun , Sugihara Takumichi , Kaneko Chikara
Published: March 2006

Direct formation of α-fluorosulfones from sulfoxides bearing α-hydrogens merely by reacting molecular fluorine (5% F2/N2) is reported and a possible mechanism for this novel α-fluorination reaction is proposed.
Stereoselective Ring Opening of Geometrically Constrained Oxaziridines by Photosensitized Electron Transfer
Authors: Iwano Yasunori , Kawamura Yasuhiko , Horie Tokunaru
Published: March 2006

Stereoselective isomerizations of geometrically constrained oxaziridines 1 to the corresponding nitrones 2 could be induced by 9,10-dicyanoanthracene-photosensitized electron transfer.
Preparation and Properties of π-Conjugated Poly(1,10-phenanthroline-3,8-diyl)
Authors: Saitoh Yutaka , Yamamoto Takakazu
Published: March 2006

Poly(1,10-phenanthroline-3,8-diyl) has been synthesized by dehalogenation polycondensation of 3,8-dibromo-1,10-phenanthroline with a zerovalent nickel complex. The polymer has molecular weight of 6800 and is electrochemically reduced at Epa = 2.24 V vs Ag/Ag+.
Qualitative evaluation of a diabetes advisory system, DiasNet
Authors: Dinesen Birthe , Andersen Povl Erik Rostgaard
Published: March 2006

We carried out a qualitative evaluation of the implementation of a computerized diabetes advisory system, DiasNet. Three patients with insulin-dependent diabetes used the system. The methodological frame of reference was the case study. Qualitative interviews were conducted with patients. In addition, 10 qualitative interviews were conducted with health-care professionals and one focus group interview was held. The study lasted for six months. The results showed that patients experienced greater confidence and a more personal rapport with the staff. DiasNet brought about changes in the tasks and duties performed by all professional groups in the diabetes team. From the perspective of the diabetes team, email facilitated a dialogue between the patient and the diabetes team which was independent of time and place.
Multicentre evaluation of a rule-based data filter for home monitoring of implanted cardioverter defibrillators
Authors: Sinha Anil-Martin , Koos Ralf , Markus Kai U , Diem Bjoern H , Urbaszek Albrecht , Hanrath Peter , Stellbrink Christoph
Published: March 2006

We developed a rule-based data filter for the automatic interpretation of data transmitted from implantable cardioverter defibrillators (ICDs). The feasibility and user acceptability of the data filter were tested in a multicentre study. Fifteen European centres analysed 10 cases each. The cases represented ICD follow-up findings, e.g. new tachycardia, battery depletion or sensing defects. The mean follow-up period was 68 days (SD 35). A questionnaire was used to collect information regarding the functionality and general concept of automatic data interpretation. A score of five or above (range 1–9) was classified as acceptable. According to the questionnaires, there was a high degree of satisfaction with the general concept of automatic data interpretation (mean 6.7, SD 1.2) and with user guidance (mean 7.1, SD 0.8). Safety (mean 7.0, SD 1.4) and accuracy (mean 6.7, SD 1.4) of the evaluation of device-related and clinical problems were regarded as high. Support in daily routine was considered to be high (mean 7.3, SD 1.1) as the system was easy to understand (mean 7.5, SD 0.9). The results indicated a high user acceptance with easy system handling.
Teledermatology reduces the number of patient referrals to a dermatologist
Authors: Knol A , van den Akker Th W , Damstra R J , de Haan J
Published: March 2006

During a two-year study, 505 teledermatology consultations were carried out on 503 patients of 29 participating general practitioners (GPs) in the province of Friesland. One overview and two detail digital photographs of the skin problems were taken on a digital camera and attached to an email message containing standard clinical information. These email messages were sent to a dermatologist, who replied by email after evaluation. After a median follow-up time of 548 days, the GPs were interviewed about the dermatological referrals. The reduction in referrals was 51% (0.95 confidence interval = 47–58%) when the GP had the intention to refer. When the GPs had no intention to refer, there turned out to be a secondary traditional consultation in 17% of cases. The reduction of 51% of referrals after store-and-forward teledermatology consultation was similar to that seen in other studies of videoconferencing. Consultation using digital store-and-forward teledermatology by the GP can halve the number of referrals to a dermatologist for selected patients.
A university oncology department and a remote palliative care unit linked together by email and videoconferencing
Authors: Norum Jan , Jordhøy Marit S
Published: March 2006

We investigated the feasibility of using email and videoconferencing for clinical and educational support between oncologists at the University Hospital of North Norway and colleagues at the oncology and palliative care unit of the Nordland Hospital in Bodø. During a 12-month period, 23 cases (20 patients) and four general questions were sent by email and 32 videoconferences were planned. Breast and colorectal cancer were the most frequent diagnoses (59%) in the email messages. Most cases (15/23) were treated locally. Although five videoconferences failed due to telecommunication and/or user problems, videoconferencing was still a success in the education of the remote oncologists in Bodø. The study demonstrated that telemedicine can be used to incorporate a remote palliative care unit into a university department.
Evaluation of digital skin images submitted by patients who received practical training or an online tutorial
Authors: Qureshi Abrar A , Brandling-Bennett Heather A , Giberti Steven , McClure Douglas , Halpern Elkan F , Kvedar Joseph C
Published: March 2006

We evaluated the ability of subjects to capture and submit teledermatology images with a digital camera. We also examined whether participants who received individual training sessions would capture better-quality images than participants who were provided only with self-training. Fifty participants were randomized between in-person training and self-training via an online tutorial. The majority of participants were young, well educated women. Two dermatologists reading the images for quality indicators had high agreement that digital images acquired were of high quality: images were well framed, appropriately bright, in focus and did not have a shadow. There was moderate agreement on diagnosis-related indicators, such as the presence or absence of pustules or papules and acne versus rosacea. There was no difference in the image-quality attributes between participants personally trained and those trained with the online tutorial. Subjects participating in this study were able to acquire images of good quality, irrespective of whether they received practical training or used an online tutorial.
Tele-education
Authors: Curran Vernon R
Published: March 2006

Tele-education has been used for many years to deliver continuing education programmes to rural health-care professionals. The main modes are audio, video and computer. Audio technologies involve the transmission of the spoken word (voice) between learners and instructors, either synchronously or asynchronously. Examples of the former include audioconferencing and short-wave radio; examples of the latter include audiotape or audiocassette. Video for distance learning, like audio, can be used in either synchronous or asynchronous fashion. Videoconferencing, or interactive television, are considered synchronous because there is the opportunity for live visual and verbal interaction between instructors and learners. Asynchronous instructional video tools include slow-scan video, interactive videodiscs and videotapes. Computer-assisted learning or instruction can be defined as any learning that is mediated by a computer and which requires no direct interaction between the user and a human instructor in order to run. It is becoming increasingly common. Examples include: the Internet and World Wide Web, email, synchronous and asynchronous computer-mediated communication applications and interactive multimedia applications on CD-ROM. Tele-education technologies have an important role to play in addressing the professional isolation which is experienced by rural and remote health-care professionals.
Two years' experience with Web-based teleconsulting in dermatology
Authors: Massone C , Soyer H P , Hofmann-Wellenhof R , Di Stefani A , Lozzi G P , Gabler G , Dong H , Argenziano G , Ozdemir F , Fink-Puches R , Salmhofer W , Zalaudek I , Nunzi E , Kerl H
Published: March 2006

A non-commercial teledermatology network based on store-and-forward operation was established in April 2002. The aim was to create an easy-to-use platform for teleconsultation services, where physicians could seek diagnostic advice in dermatology from a pool of expert consultants and where they could present and discuss challenging dermatology cases with special emphasis on diagnosis and therapy. An online moderated discussion forum was added in October 2003. During the first two years, 348 health-care professionals from 45 countries registered to use the Website. A total of 783 requests for consultations were answered; 285 requests concerned pigmented skin lesions, 440 requests were from the whole range of clinical dermatology and 58 requests were about non-melanoma skin cancer. Of a total of 133 requests analysed, 80 (60%) were answered within one day, 47 (35%) within one week, five (4%) within two weeks and one (1%) consultation was answered in more than two weeks. Our experience with a discretionary, non-commercial, multilingual Website for open-access teleconsulting in dermatology appears to be successful. The Website represents an example of user-generated content, together with active interaction between users, who can present and discuss cases with remote colleagues.
Solution structure of an informationally complex high-affinity RNA aptamer to GTP
Authors: CAROTHERS JAMES M. , DAVIS JONATHAN H. , CHOU JAMES J. , SZOSTAK JACK W.
Published: March 2006

Higher-affinity RNA aptamers to GTP are more informationally complex than lower-affinity aptamers. Analog binding studies have shown that the additional information needed to improve affinity does not specify more interactions with the ligand. In light of those observations, we would like to understand the structural characteristics that enable complex aptamers to bind their ligands with higher affinity. Here we present the solution structure of the 41-nt Class I GTP aptamer (Kd = 75 nM) as determined by NMR. The backbone of the aptamer forms a reverse-S that shapes the binding pocket. The ligand nucleobase stacks between purine platforms and makes hydrogen bonds with the edge of another base. Interestingly, the local modes of interaction for the Class I aptamer and an RNA aptamer that binds ATP with a Kdof 6 μM are very much alike. The aptamers exhibit nearly identical levels of binding specificity and fraction of ligand sequestered from the solvent (81%–85%). However, the GTP aptamer is more informationally complex (~45 vs. 35 bits) and has a larger recognition bulge (15 vs. 12 nucleotides) with many more stabilizing base–base interactions. Because the aptamers have similar modes of ligand binding, we conclude that the stabilizing structural elements in the Class I aptamer are responsible for much of the difference in Kd. These results are consistent with the hypothesis that increasing the number of intra-RNA interactions, rather than adding specific contacts to the ligand, is the simplest way to improve binding affinity.
Research Note—The Benefits of Personalized Pricing in a Channel
Authors: Liu Yunchuan , Zhang Z. John
Published: March 2006

In this note, we explore channel interactions in an information-intensive environment where the retailer can implement personalized pricing and the manufacturer can leverage both personalized pricing and entry into a direct distribution channel. We study whether a retailer can benefit from personalized pricing and how upstream personalized pricing or entry into a direct distribution channel affects the allocation of channel profit. We find that the retailer is worse off because of its own or upstream personalized pricing, even when the retailer is a monopoly. However, it may still be optimal for the retailer to embrace personalized pricing in order to reap the strategic benefit of deterring the manufacturer from selling direct and targeting end consumers.
Setting Quality Expectations When Entering a Market: What Should the Promise Be?
Authors: Kopalle Praveen K. , Lehmann Donald R.
Published: March 2006

This paper examines optimal advertised quality, actual quality, and price for a firm entering a market. It develops a two-period model where advertised quality influences expectations, and hence trial and the gap between actual quality and expectations determines satisfaction, which in turn impacts second-period sales. In such situations a company makes a choice between advertising high quality and getting trial, but little repeat; and advertising low quality and getting low trial, but high repeat.

Results are derived by numerical methods, as well as analytically for a special case of the model. The model suggests it is optimal to overstate quality when (i) customers rely relatively less on advertising to form quality expectations, and (ii) customers’ intrinsic satisfaction with a product is high.

These results are consistent with deceptive advertising cases at the FTC, which showed more deception for unknown firms and for firms whose customers were more satisfied. They are also consistent with the decisions made by future managers (MBAs), except that the respondents would advertise higher (versus lower) quality when advertising was effective.
How to Compute Optimal Catalog Mailing Decisions
Authors: Gönül Füsun F. , Hofstede Frenkel Ter
Published: March 2006

We develop, estimate, and test a response model of order timing and order volume decisions of catalog customers and derive a Bayes rule for optimal mailing strategies. The model integrates the when and how much components of the response; incorporates the mailing decision of the firm; and uses a Bayesian framework to determine the optimal mailing rule for each catalog customer. The Bayes rule we propose for optimal mailing strategy allows for a broad set of objectives to be realized across the time horizon, such as profit maximization, customer retention, and utility maximization with or without risk aversion. We find that optimizing the objective function over multiple periods as opposed to a single period leads to higher expected profits and expected utility. Our results indicate that the cataloguer is well advised to send fewer catalogs than its current practice in order to maximize expected profits and utility.
An Empirical Model of Optimal Dynamic Product Launch and Exit Under Demand Uncertainty
Authors: Hitsch Günter J.
Published: March 2006

This paper considers the decision problem of a firm that is uncertain about the demand, and hence profitability, of a new product. We develop a model of a decision maker who sequentially learns about the true product profitability from observed product sales. Based on the current information, the decision maker decides whether to scrap the product. Central to this decision problem are sequential information gathering, and the option value of scrapping the product at any point in time. The model predicts the optimal demand for information (e.g., in the form of test marketing), and it predicts how the launch or exit policy depends on the firm’s demand uncertainty. Furthermore, it predicts what fraction of newly developed products should be launched on average, and what fraction of these products will “fail,” i.e., exit. The model is solved using numerical dynamic programming techniques. We present an application of the model to the case of the U.S. ready-to-eat breakfast cereal industry. Simulations show that the value of reducing uncertainty can be large, and that under higher uncertainty firms should strongly increase the fraction of all new product opportunities launched, even if their point estimate of profits is negative. Alternative, simpler decision rules are shown to lead to large profit losses compared to our method. Finally, we find that the high observed exit rate in the U.S. ready-to-eat cereal industry is optimal and to be expected based on our model.