bluuebunny/crossref_metadata_2025 huggingface dataset:
Carbonate nodules of probable stromatolitic origin in amphibolite from the Neoproterozoic terrain of southern Israel
Authors: Bogoch R. , Shirav M.
Published: October 2004

Several small bodies of massive to banded amphibolite occur within plagioclase-quartz-biotite hornblende gneiss at or close to its boundary with a quartz diorite pluton in the Neoproterozoic terrain of southern Israel. Entrapped within the amphibolite are nodules consisting mainly of calcite+talc, and rare banded marble. Remnant laminae and certain geochemical features such as the negative Ce anomaly and depleted δ13C of the nodules sugggest that they initially formed as stromatolites. The local geological setting of the amphibolites together with the presence of the enclosed meta-carbonates favoured an origin as sediments, although some of the geochemical data point to a basaltic precursor and some of the carbonates have a puzzlingly high (>1000 ppm) Ni content. The origin of the amphibolites is thus enigmatic.
Suprasubduction-zone peridotite in the northern USA Appalachians: evidence from mineral composition
Authors: Coish R. A. , Gardner P.
Published: October 2004

Mineral compositions of small peridotite bodies in an Ordovician collision zone of the Vermont Appalachians provide important clues to their tectonic environment of origin. The bodies have been deformed and partially serpentinized under greenschist- to lower amphibolite-facies conditions during the Ordovician and Devonian. Before serpentinization, the peridotite bodies were dunite as shown by their mineral assemblage and by their high MgO, and low Ti and Al whole-rock contents. Despite deformation and metamorphism, remnant olivine and spinel grains occur; their compositions are taken to represent conditions prior to regional metamorphic events. High Mg/(Mg+Fe) in olivine and very high Cr/(Cr+Al) in spinel indicate that the peridotites formed as highly-depleted mantle residues. The compositions are similar to those in harzburgite and dunite from some ophiolites and from fore-arc regions of subduction zones. Accordingly, the southern Vermont peridotites probably formed in a forearc, supra-subduction zone during the Early Palaeozoic. They were subsequently emplaced by obduction of the upper plate of an east-facing subduction complex.
Apolipoprotein A-I infiltration in rheumatoid arthritis synovial tissue: a control mechanism of cytokine production?
Authors: Bresnihan Barry , Gogarty Martina , FitzGerald Oliver , Dayer Jean-Michel , Burger Danielle
Published: October 2004

The production of tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) by monocytes is strongly induced by direct contact with stimulated T lymphocytes, and this mechanism may be critical in the pathogenesis of rheumatoid arthritis (RA). Apolipoprotein A-I (apoA-I) blocks contact-mediated activation of monocytes, causing inhibition of TNF-α and IL-1β production. This study examined the hypothesis that apoA-I may have a regulatory role at sites of macrophage activation by T lymphocytes in inflamed RA synovial tissue. Synovial tissue samples were obtained after arthroscopy from patients with early untreated RA or treated RA and from normal subjects. As determined by immunohistochemistry, apoA-I was consistently present in inflamed synovial tissue that contained infiltrating T cells and macrophages, but it was absent from noninflamed tissue samples obtained from treated patients and from normal subjects. ApoA-I staining was abundant in the perivascular areas and extended in a halo-like pattern to the surrounding cellular infiltrate. C-reactive protein and serum amyloid A were not detected in the same perivascular areas of inflamed tissues. The abundant presence of apoA-I in the perivascular cellular infiltrates of inflamed RA synovial tissue extends the observations in vitro that showed that apoA-I can modify contact-mediated macrophage production of TNF-α and IL-1β. ApoA-I was not present in synovium from patients in apparent remission, suggesting that it has a specific role during phases of disease activity. These findings support the suggestion that the biologic properties of apoA-I, about which knowledge is newly emerging, include anti-inflammatory activities and therefore have important implications for the treatment of chronic inflammatory diseases.
Proteotypic classification of spontaneous and transgenic mammary neoplasms
Authors: Mikaelian Igor , Blades Natalie , Churchill Gary A , Fancher Karen , Knowles Barbara B , Eppig Janan T , Sundberg John P
Published: October 2004

Introduction

Mammary tumors in mice are categorized by using morphologic and architectural criteria. Immunolabeling for terminal differentiation markers was compared among a variety of mouse mammary neoplasms because expression of terminal differentiation markers, and especially of keratins, provides important information on the origin of neoplastic cells and their degree of differentiation.

Methods

Expression patterns for terminal differentiation markers were used to characterize tumor types and to study tumor progression in transgenic mouse models of mammary neoplasia (mice overexpressing Neu (Erbb2), Hras, Myc, Notch4, SV40-TAg, Tgfa, and Wnt1), in spontaneous mammary carcinomas, and in mammary neoplasms associated with infection by the mouse mammary tumor virus (MMTV).

Results

On the basis of the expression of terminal differentiation markers, three types of neoplasm were identified: first, simple carcinomas composed exclusively of cells with a luminal phenotype are characteristic of neoplasms arising in mice transgenic for Neu, Hras, Myc, Notch4, and SV40-TAg; second, 'complex carcinomas' displaying luminal and myoepithelial differentiation are characteristic of type P tumors arising in mice transgenic for Wnt1, neoplasms arising in mice infected by the MMTV, and spontaneous adenosquamous carcinomas; and third, 'carcinomas with epithelial to mesenchymal transition (EMT)' are a characteristic feature of tumor progression in Hras-, Myc-, and SV40-TAg-induced mammary neoplasms and PL/J and SJL/J mouse strains, and display de novo expression of myoepithelial and mesenchymal cell markers. In sharp contrast, EMT was not detected in papillary adenocarcinomas arising in BALB/cJ mice, spontaneous adenoacanthomas, neoplasms associated with MMTV-infection, or in neoplasms arising in mice transgenic for Neu and Wnt1.

Conclusions

Immunohistochemical profiles of complex neoplasms are consistent with a stem cell origin, whereas simple carcinomas might originate from a cell committed to the luminal lineage. In addition, these results suggest that the initiating oncogenic events determine the morphologic features associated with cancer progression because EMT is observed only in certain types of neoplasm.
Effect of lung compliance and endotracheal tube leakage on measurement of tidal volume
Authors: Al-Majed Sami I , Thompson John E , Watson Kenneth F , Randolph Adrienne G
Published: October 2004

Introduction

The objective of this laboratory study was to measure the effect of decreased lung compliance and endotracheal tube (ETT) leakage on measured exhaled tidal volume at the airway and at the ventilator, in a research study with a test lung.

Methods

The subjects were infant, adult and pediatric test lungs. In the test lung model, lung compliances were set to normal and to levels seen in acute respiratory distress syndrome. Set tidal volume was 6 ml/kg across a range of simulated weights and ETT sizes. Data were recorded from both the ventilator light-emitting diode display and the CO2SMO Plus monitor display by a single observer. Effective tidal volume was calculated from a standard equation.

Results

In all test lung models, exhaled tidal volume measured at the airway decreased markedly with decreasing lung compliance, but measurement at the ventilator showed minimal change. In the absence of a simulated ETT leak, calculation of the effective tidal volume led to measurements very similar to exhaled tidal volume measured at the ETT. With a simulated ETT tube leak, the effective tidal volume markedly overestimated tidal volume measured at the airway.

Conclusion

Previous investigators have emphasized the need to measure tidal volume at the ETT for all children. When ETT leakage is minimal, it seems from our simulated lung models that calculation of effective tidal volume would give similar readings to tidal volume measured at the airway, even in small patients. Future studies of tidal volume measurement accuracy in mechanically ventilated children should control for the degree of ETT leakage.
Metabolic Syndrome Is Associated with Elevated Oxidative Stress and Dysfunctional Dense High-Density Lipoprotein Particles Displaying Impaired Antioxidative Activity
Authors: Hansel Boris , Giral Philippe , Nobecourt Estelle , Chantepie Sandrine , Bruckert Eric , Chapman M. John , Kontush Anatol
Published: October 2004

A metabolic syndrome (MetS) phenotype is characterized by insulin-resistance, atherogenic dyslipidemia, oxidative stress, and elevated cardiovascular risk and frequently involves subnormal levels of high-density lipoprotein (HDL) cholesterol. We evaluated the capacity of physicochemically distinct HDL subfractions from MetS subjects to protect low-density lipoprotein against oxidative stress.

MetS subjects presented an insulin-resistant phenotype, with central obesity and elevation in systolic blood pressure and plasma triglyceride, LDL-cholesterol, apolipoprotein B, glucose, and insulin levels. Systemic oxidative stress, assessed as plasma 8-isoprostanes, was significantly higher (3.7-fold) in MetS subjects (n = 10) compared with nonobese normolipidemic controls (n = 11). In MetS, small, dense HDL3a, 3b, and 3c subfractions possessed significantly lower specific antioxidative activity (up to −23%, on a unit particle mass basis) than their counterparts in controls. In addition, HDL2a and 3a subfractions from MetS patients possessed lower total antioxidative activity (up to −41%, at equivalent plasma concentrations). The attenuated antioxidative activity of small, dense HDL subfractions correlated with systemic oxidative stress and insulin resistance and was associated with HDL particles exhibiting altered physicochemical properties (core triglyceride enrichment and cholesteryl ester depletion).

We conclude that antioxidative activity of small, dense HDL subfractions of altered chemical composition is impaired in MetS and associated with elevated oxidative stress and insulin resistance. Induction of selective increase in the circulating concentrations of dense HDL subfractions may represent an innovative therapeutic approach for the attenuation of high cardiovascular risk in MetS.
A Case of Chromosome 22q11 Deletion Syndrome Diagnosed in a 32-Year-Old Man with Hypoparathyroidism
Authors: Maalouf Naim M. , Sakhaee Khashayar , Odvina Clarita V.
Published: October 2004

Congenital hypoparathyroidism typically manifests with hypocalcemia with or without associated characteristic physical findings and is usually diagnosed during the neonatal period. This report describes an African-American male who was diagnosed at age 32 yr to have dysgenesis of the parathyroid glands due to chromosome 22 microdeletion. Symptomatic hypocalcemia did not develop until age 14 yr, a few weeks after initiation of anticonvulsant therapy for generalized tonic-clonic seizures. Because of the timing for onset of symptomatic hypocalcemia, it was presumed that the patient had anticonvulsant-induced hypocalcemia, and he carried that diagnosis for 18 yr. Chromosome 22q11 deletion syndrome was first suspected at age 32 yr, based on the findings of subtle dysmorphic facial features and a history of learning disability in a patient with PTH-deficient hypocalcemia. The diagnosis was confirmed by fluorescence in situ hybridization analysis.

This case underscores the variable clinical presentation of this congenital form of hypoparathyroidism. Chromosome 22q11 microdeletions are relatively common, and the diagnosis should be considered even in adults with hypoparathyroidism because of the potential benefit of genetic counseling.
Growth Hormone Treatment Improves Peripheral Muscle Oxygen Extraction-Utilization during Exercise in Patients with Human Immunodeficiency Virus-Associated Wasting: A Randomized Controlled Trial
Authors: Esposito John G. , Thomas Scott G. , Kingdon Lori , Ezzat Shereen
Published: October 2004

The arteriovenous oxygen difference (a-vO2 difference), a measure of peripheral muscle oxygen extraction-utilization during exercise, is reduced in antiretroviral-treated patients with human immunodeficiency virus (HIV), thus causing a shift in the cardiac output-oxygen consumption (Q-VO2) relationship. We investigated the impact of recombinant human GH (rhGH) treatment on a-vO2 difference and the Q-VO2 relationship during submaximal exercise by randomizing 12 HIV-infected patients (mean ± sem: age, 43.3 ± 1.5 yr; body mass, 69.5 ± 2.9 kg; body mass index, 22.4 ± 0.9 kg/m2; maximum oxygen consumption, 33.6 ± 1.5 ml/kg·min), with documented unintentional weight loss (≥10% within the preceding 12 months) despite antiretroviral therapy, to receive 3 months of rhGH (6 mg/d) in a double-blind, placebo-controlled, cross-over trial. We assessed Q (determined noninvasively using CO2 rebreathing), and subsequently a-vO2 difference, from Q-VO2 relationships. At study entry, the mean slope (8.1 ± 1.0 liters/min·1-liter increase in VO2) and intercept (3.1 ± 1.3 liters/min), generated from each patient’s Q-VO2 relationship, were greater and lower, respectively, than those reported for healthy individuals (6.0 and 4.0, respectively), thereby indicating a deficit in the a-vO2 difference. After 3 months of rhGH treatment, the slope decreased to 7.0, and the intercept increased to 3.5. After 1 month of rhGH treatment, the a-vO2 difference (at a VO2 of 1250 ml/min) significantly (P < 0.05) increased (17.1 ± 8.9%) from baseline (9.92 ± 0.51 ml/dl) and remained elevated (10.39 ± 0.48 ml/dl) after 3 months of treatment. No significant changes were seen with placebo. Therefore, treatment with rhGH leads to an improvement in peripheral muscle oxygen extraction-utilization and the Q-VO2 relationship during exercise in patients with HIV-associated wasting despite antiretroviral therapy.
Gonadal Dysgenesis Without Adrenal Insufficiency in a 46, XY Patient Heterozygous for the Nonsense C16X Mutation: A Case of SF1 Haploinsufficiency
Authors: Mallet Delphine , Bretones Patricia , Michel-Calemard Laurence , Dijoud Frederique , David Michel , Morel Yves
Published: October 2004

Targeted disruption of the orphan nuclear receptor SF1 results in the absence of adrenals and gonads, establishing that this transcription factor is implicated in gonadal determination and adrenal development. Four human SF1 gene mutations have been described to date: three (G35E, R92Q, R255L) were responsible for adrenal insufficiency associated with a gonadal dysgenesis in two 46, XY individuals, one (8 bp deletion in exon 6) resulted in gonadal dysgenesis without adrenal insufficiency. We identified a new heterozygous SF1 gene mutation, C16X, in a 46, XY patient showing gonadal dysgenesis with normal adrenal function: low basal levels of AMH and testosterone (T), weak T response to hCG, hypoplastic testes with abundant seminiferous tubules but rare germ cells. This mutation causes premature termination of translation and should abolish all SF1 activity. Therefore haploinsufficiency could explain the deleterious effect of this mutation in our patient suggesting that testis development is more SF1 dose-dependant than adrenal development. Although the same mechanism explains the deleterious effects of SF1 missense mutations, recent studies have demonstrated an additional dominant negative effect. These data suggest that heterozygous mutation impaired adrenal development only if the two mechanisms, gene dosage and dominant negative effects occur.
Tbx1 regulates fibroblast growth factors in the anterior heart field through a reinforcing autoregulatory loop involving forkhead transcription factors
Authors: Hu Tonghuan , Yamagishi Hiroyuki , Maeda Jun , McAnally John , Yamagishi Chihiro , Srivastava Deepak
Published: October 2004

Birth defects, which occur in one out of 20 live births, often affect multiple organs that have common developmental origins. Human and mouse studies indicate that haploinsufficiency of the transcription factor TBX1 disrupts pharyngeal arch development, resulting in the cardiac and craniofacial features associated with microdeletion of 22q11 (del22q11), the most frequent human deletion syndrome. Here, we have generated an allelic series of Tbx1 deficiency that reveals a lower critical threshold for Tbx1 activity in the cardiac outflow tract compared with other pharyngeal arch derivatives, including the palatal bones. Mice hypomorphic for Tbx1 failed to activate expression of the forkhead transcription factor Foxa2 in the pharyngeal mesoderm, which contains cardiac outflow precursors derived from the anterior heart field. We identified a Fox-binding site upstream of Tbx1 that interacted with Foxa2 and was necessary for pharyngeal mesoderm expression of Tbx1, revealing an autoregulatory loop that may explain the increased cardiac sensitivity to Tbx1 dose. Downstream of Tbx1, we found a fibroblast growth factor 8 (Fgf8) enhancer that was dependent on Tbx1 in vivo for regulating expression in the cardiac outflow tract, but not in pharyngeal arches. Consistent with its role in regulating cardiac outflow tract cells Tbx1 gain of function resulted in expansion of the cardiac outflow tract segment derived from the anterior heart field as marked by Fgf10. These findings reveal a Tbx1-dependent transcriptional and signaling network in the cardiac outflow tract that renders mouse cardiovascular development more susceptible than craniofacial development to a reduction in Tbx1 dose, similar to humans with del22q11.
Skeletal defects inringelschwanzmutant mice reveal that Lrp6 is required for proper somitogenesis and osteogenesis
Authors: Kokubu Chikara , Heinzmann Ulrich , Kokubu Tomoko , Sakai Norio , Kubota Takuo , Kawai Masanobu , Wahl Matthias B. , Galceran Juan , Grosschedl Rudolf , Ozono Keiichi , Imai Kenji
Published: October 2004

Here, we present evidence that Lrp6, a coreceptor for Wnt ligands, is required for the normal formation of somites and bones. By positional cloning,we demonstrate that a novel spontaneous mutation ringelschwanz(rs) in the mouse is caused by a point mutation in Lrp6,leading to an amino acid substitution of tryptophan for the evolutionarily conserved residue arginine at codon 886 (R886W). We show that rs is a hypomorphic Lrp6 allele by a genetic complementation test with Lrp6-null mice, and that the mutated protein cannot efficiently transduce signals through the Wnt/β-catenin pathway. Homozygous rs mice, many of which are remarkably viable, exhibit a combination of multiple Wnt-deficient phenotypes, including dysmorphologies of the axial skeleton, digits and the neural tube. The establishment of the anteroposterior somite compartments, the epithelialization of nascent somites, and the formation of segment borders are disturbed in rs mutants, leading to a characteristic form of vertebral malformations, similar to dysmorphologies in individuals suffering from spondylocostal dysostosis. Marker expression study suggests that Lrp6 is required for the crosstalk between the Wnt and notch-delta signaling pathways during somitogenesis. Furthermore, the Lrp6 dysfunction in rs leads to delayed ossification at birth and to a low bone mass phenotype in adults. Together, we propose that Lrp6 is one of the key genetic components for the pathogenesis of vertebral segmentation defects and of osteoporosis in humans.
DrosophilaEpsin mediates a select endocytic pathway that DSL ligands must enter to activate Notch
Authors: Wang Weidong , Struhl Gary
Published: October 2004

Recent findings suggest that Delta/Serrate/Lag2 (DSL) signals activate Notch by an unprecedented mechanism that requires the ligands to be endocytosed in signal-sending cells to activate the receptor in signal-receiving cells. Here, we show that cells devoid of Epsin, a conserved adaptor protein for Clathrin-mediated endocytosis, behave normally except that they cannot send DSL signals. Surprisingly, we find that Epsin is not required for bulk endocytosis of DSL proteins. Instead, Epsin appears to be essential for targeting DSL proteins to a special endocytic pathway that they must enter to acquire signaling activity. We present evidence that DSL proteins must be mono-ubiquitinated to be targeted by Epsin to this pathway. Furthermore, we show that the requirements for both Epsin and mono-ubiquitination can be bypassed by introducing the internalization signal that mediates endocytosis and recycling of the Low Density Lipoprotein (LDL) receptor. We propose that Epsin is essential for DSL signaling because it targets mono-ubiquitinated DSL proteins to an endocytic recycling compartment that they must enter to be converted into active ligands. Alternatively Epsin may be required to target mono-ubiquitinated DSL proteins to a particular subclass of coated pits that have special properties essential for Notch activation.
Specification ofDrosophilamotoneuron identity by the combinatorial action of POU and LIM-HD factors
Authors: Certel Sarah J. , Thor Stefan
Published: October 2004

In both vertebrates and invertebrates, members of the LIM-homeodomain(LIM-HD) family of transcription factors act in combinatorial codes to specify motoneuron subclass identities. In the developing Drosophila embryo,the LIM-HD factors Islet (Tailup) and Lim3, specify the set of motoneuron subclasses that innervate ventral muscle targets. However, as several subclasses express both Islet and Lim3, this combinatorial code alone cannot explain how these motoneuron groups are further differentiated. To identify additional factors that may act to refine this LIM-HD code, we have analyzed the expression of POU genes in the Drosophila embryonic nerve cord. We find that the class III POU protein, Drifter (Ventral veinless), is co-expressed with Islet and Lim3 specifically in the ISNb motoneuron subclass. Loss-of-function and misexpression studies demonstrate that the LIM-HD combinatorial code requires Drifter to confer target specificity between the ISNb and TN motoneuron subclasses. To begin to elucidate molecules downstream of the LIM-HD code, we examined the involvement of the Beaten path (Beat)family of immunoglobulin-containing cell-adhesion molecules. We find that beat Ic genetically interacts with islet and Lim3in the TN motoneuron subclass and can also rescue the TN fasciculation defects observed in islet and Lim3 mutants. These results suggest that in the TN motoneuron context, Islet and Lim3 may specify axon target selection through the actions of IgSF call-adhesion molecules.
FGF and PI3 kinase signaling pathways antagonistically modulate sex muscle differentiation inC. elegans
Authors: Sasson Isaac E. , Stern Michael J.
Published: October 2004

Myogenesis in vertebrate myocytes is promoted by activation of the phosphatidyl-inositol 3′-kinase (PI3 kinase) pathway and inhibited by fibroblast growth factor (FGF) signaling. We show that hyperactivation of the Caenorhabditis elegans FGF receptor, EGL-15, similarly inhibits the differentiation of the hermaphrodite sex muscles. Activation of the PI3 kinase signaling pathway can partially suppress this differentiation defect,mimicking the antagonistic relationship between these two pathways known to influence vertebrate myogenesis. When ectopically expressed in body wall muscle precursor cells, hyperactivated EGL-15 can also interfere with the proper development of the body wall musculature. Hyperactivation of EGL-15 has also revealed additional effects on a number of fundamental processes within the postembryonic muscle lineage, such as cell division polarity. These studies provide important in vivo insights into the contribution of FGF signaling events to myogenesis.
Morphogenesis in the absence of integrins: mutation of bothDrosophilaβ subunits prevents midgut migration
Authors: Devenport Danelle , Brown Nicholas H.
Published: October 2004

Two integrin β subunits are encoded in the Drosophila genome. The βPS subunit is widely expressed and heterodimers containing this subunit are required for many developmental processes. The second βsubunit, βν, is a divergent integrin expressed primarily in the midgut endoderm. To elucidate its function, we generated null mutations in the gene encoding βν. We find that βν is not required for viability or fertility, and overall the mutant flies are normal in appearance. However, we could observe βν function in the absence of βPS. Consistent with its expression, removal of βν only enhanced the phenotype of βPS in the developing midgut. In embryos lacking the zygotic contribution ofβPS, loss of βν resulted in enhanced separation between the midgut and the surrounding visceral mesoderm. In the absence of both maternal and zygotic βPS, a delay in midgut migration was observed, but removingβν as well blocked migration completely. These results demonstrate that the second β subunit can partially compensate for loss of βPS integrins, and that integrins are essential for migration of the primordial midgut cells. The two β subunits mediate midgut migration by distinct mechanisms: one that requires talin and one that does not. Other examples of developmental cell migration, such as that of the primordial germ cells,occurred normally in the absence of integrins. Having generated the tools to eliminate integrin function completely, we confirm that Drosophilaintegrins do not control proliferation as they do in mammals, and have identified αPS3 as a heterodimeric partner for βν.
Id4regulates neural progenitor proliferation and differentiation in vivo
Authors: Yun Kyuson , Mantani Akio , Garel Sonia , Rubenstein John , Israel Mark A.
Published: October 2004

The mechanisms that determine whether a precursor cell re-enters the cell cycle or exits and differentiates are crucial in determining the types and numbers of cells that constitute a particular organ. Here, we report that Id4 is required for normal brain size, and regulates lateral expansion of the proliferative zone in the developing cortex and hippocampus. In its absence, proliferation of stem cells in the ventricular zone (VZ) is compromised. In early cortical progenitors, Id4 is required for the normal G1-S transition. By contrast, at later ages, ectopically positioned proliferating cells are found in the mantle zone of the Id4-/- cortex. These observations, together with evidence for the premature differentiation of early cortical stem cells, indicate that Id4 has a unique and complex function in regulating neural stem cell proliferation and differentiation.
Fat facets and Liquid facets promote Delta endocytosis and Delta signaling in the signaling cells
Authors: Overstreet Erin , Fitch Erin , Fischer Janice A.
Published: October 2004

Endocytosis modulates the Notch signaling pathway in both the signaling and receiving cells. One recent hypothesis is that endocytosis of the ligand Delta by the signaling cells is essential for Notch activation in the receiving cells. Here, we present evidence in strong support of this model. We show that in the developing Drosophila eye Fat facets (Faf), a deubiquitinating enzyme, and its substrate Liquid facets (Lqf), an endocytic epsin, promote Delta internalization and Delta signaling in the signaling cells. We demonstrate that while Lqf is necessary for three different Notch/Delta signaling events at the morphogenetic furrow, Faf is essential only for one:Delta signaling by photoreceptor precluster cells, which prevents recruitment of ectopic neurons. In addition, we show that the ubiquitin-ligase Neuralized(Neur), which ubiquitinates Delta, functions in the signaling cells with Faf and Lqf. The results presented bolster one model for Neur function in which Neur enhances Delta signaling by stimulating Delta internalization in the signaling cells. We propose that Faf plays a role similar to that of Neur in the Delta signaling cells. By deubiquitinating Lqf, which enhances the efficiency of Delta internalization, Faf stimulates Delta signaling.
Motor output characterizing thanatosis in the cricketGryllus bimaculatus
Authors: Nishino Hiroshi
Published: October 2004

The cricket Gryllus bimaculatus displays a sudden rigid immobility(thanatosis) when voluntary leg movements are forcibly restrained. The tibial joints in all legs are stiffly immobilized for several minutes. The flexed-leg posture typical of thanatosis is maintained by the flexor tibiae muscle. To characterize thanatosis at the motor output level, the mechanical and physiological properties of the metathoracic tibia muscle were investigated. The accessory flexor muscle, especially well-developed in the cricket, acts to stably maintain the tibial flexion driven by the main flexor muscle. Extracellular recordings from the flexor muscle of tethered crickets revealed that activity of intermediate- and fast-excitatory units was almost completely suppressed, while slow-excitatory units persisted in firing tonically during thanatosis. The firing rate of slow-excitatory units progressively increased as the tibia flexed, but remained less than the firing rate seen in the quiescent state. Common inhibitory motor neurones that fire sporadically in the quiescent state were suppressed during thanatosis, especially in the beginning, and showed a large excitation immediately after arousal. These findings suggest that the entire motor neuronal pool is held under active suppression during thanatosis, and that flexor muscle rigidity is maintained by a weak discharge of the slow exciters together with suppression of the inhibitors.
Characterization of the voltage-activated currents in cultured atrial myocytes isolated from the heart of the common oysterCrassostrea gigas
Authors: Pennec Jean-Pierre , Talarmin Hélène , Droguet Mikaël , Giroux-Metgès Marie-Agnès , Gioux Maxime , Dorange Germaine
Published: October 2004

Using the macro-patch clamp technique, we show that cardiac myocytes isolated from the heart of the oyster Crassostrea gigas possess several types of voltage-activated ionic currents. (1) A classical non-inactivating potassium current of the IK type that is inhibited by tetraethyl ammonium and shows an outward rectification and a slow activation. (2) A potassium current of the IA type that shows rapid activation and inactivation, and is blocked by 4-amino pyridine or preliminary depolarisation. (3) A potassium calcium-dependent current that is inhibited by charybdotoxin, activated by strong depolarisations and shows a large conductance. (4) A calcium inward current of the L-type that is inhibited by verapamil, cobalt and high concentrations of cadmium. This current is identified in most cells, but a T-type calcium current and classical fast sodium current are only identified in few cells, and only after a strong hyperpolarizing pulse. This suggests that these channels are normally inactivated in cultured cells and are not involved in the spontaneous activity of these cells. When they exist, the fast sodium channel is blocked by tetrodotoxin. The L-type calcium conductance is increased by serotonin. The identification in cultured oyster atrial cells of classical ionic currents,which are observed in most vertebrate species but only in a few species of molluscs, demonstrates that these cells are an interesting model. Moreover the viability and the electrophysiological properties of these cells are not significantly modified by freezing and thawing, thus increasing their usefulness in various bioassays.
Developmental changes in cardiorespiratory patterns associated with terrestrial apnoeas in harbour seal pups
Authors: Lapierre Jennifer L. , Schreer Jason F. , Burns Jennifer M. , Hammill Michael O.
Published: October 2004

During the nursing period seals undergo several physiological and behavioural changes. A key component of development is increased cardiorespiratory control, fundamental for breath-holding and thus diving. This study focused on the ontogenetic changes in cardiac responses to respiration in quietly resting, pre-weaned harbour seal pups (Phoca vitulina). During periods of quiet rest, breathing became episodic,eupnoea interspersed with periods of apnoea. Little change was observed in respiration (∼35 breaths min–1) and eupnoeic heart rate(∼160 beats min–1) throughout the nursing period. However, apnoea duration increased (from ∼20 to 40 s), while apnoeic heart rate decreased with age (from ∼150 to 90 beats min–1). The observed decline in apnoeic heart rate resulted from an increase in cardiorespiratory control as pups approached weaning, evident by the ability to maintain a lower heart rate more consistently. Similar changes in cardiorespiratory patterns have been reported for elephant and Weddell seals. Due to the early onset of independent foraging, however, the rate of cardiorespiratory control development was more rapid in harbour seals. Our findings suggest that by 1 month of age, harbour seal pups possess the cardiorespiratory control necessary to sustain long-duration apnoeas,fundamental for proficient diving and successful foraging upon weaning.
Acclimatization to 4100 m does not change capillary density or mRNA expression of potential angiogenesis regulatory factors in human skeletal muscle
Authors: Lundby Carsten , Pilegaard Henriette , Andersen Jesper L. , van Hall Gerrit , Sander Mikael , Calbet Jose A. L.
Published: October 2004

Increased skeletal muscle capillary density would be a logical adaptive mechanism to chronic hypoxic exposure. However, animal studies have yielded conflicting results, and human studies are sparse. Neoformation of capillaries is dependent on endothelial growth factors such as vascular endothelial growth factor (VEGF), a known target gene for hypoxia inducible factor 1 (HIF-1). We hypothesised that prolonged exposure to high altitude increases muscle capillary density and that this can be explained by an enhanced HIF-1αexpression inducing an increase in VEGF expression. We measured mRNA levels and capillary density in muscle biopsies from vastus lateralis obtained in sea level residents (SLR; N=8) before and after 2 and 8 weeks of exposure to 4100 m altitude and in Bolivian Aymara high-altitude natives exposed to approximately 4100 m altitude (HAN; N=7). The expression of HIF-1α or VEGF mRNA was not changed with prolonged hypoxic exposure in SLR, and both genes were similarly expressed in SLR and HAN. In SLR, whole body mass, mean muscle fibre area and capillary to muscle fibre ratio remained unchanged during acclimatization. The capillary to fibre ratio was lower in HAN than in SLR (2.4±0.1 vs 3.6±0.2; P<0.05). In conclusion, human muscle VEGF mRNA expression and capillary density are not significantly increased by 8 weeks of exposure to high altitude and are not increased in Aymara high-altitude natives compared with sea level residents.
Morphology predicts suction feeding performance in centrarchid fishes
Authors: Carroll Andrew M. , Wainwright Peter C. , Huskey Stephen H. , Collar David C. , Turingan Ralph G.
Published: October 2004

Suction feeding fish differ in their capacity to generate subambient pressure while feeding, and these differences appear to relate to morphological variation. We developed a morphological model of force transmission in the fish head and parameterized it with measurements from individual fish. The model was applied to 45 individuals from five species of centrarchid fishes: Lepomis macrochirus, Lepomis punctatus, Lepomis microlophus, Micropterus salmoides and Pomoxis nigromaculatus. Measurements of epaxial cross-sectional area, epaxial moment arm, buccal area and buccal area moment arm were combined to estimate pressure generation capacity for individual fish. This estimation was correlated with pressure measured in fish feeding on elusive prey to test the model's ability to predict pressure generation from morphology. The model explained differences in pressure generation found among individuals (P<0.001, r2=0.71) and produced a realistic estimate of normalized muscle stress during suction feeding (68.5±6.7 kPa). Fish with smaller mouths, larger epaxial cross-sectional area and longer epaxial moments, such as L. macrochirus (bluegill sunfish), generated lower pressures than fish with larger mouths, smaller cross-sectional area and shorter moments,such as M. salmoides (largemouth bass). These results reveal a direct trade-off between morphological requirements of feeding on larger prey (larger mouth size relative to body depth) and the ability to generate subambient pressure while suction feeding on elusive prey.
The effects of head and tail stimulation on the withdrawal startle response of the rope fish (Erpetoichthys calabaricus)
Authors: Bierman Hilary S. , Schriefer Julie E. , Zottoli Steven J. , Hale Melina E.
Published: October 2004

While most actinopterygian fishes perform C-start or S-start behaviors as their primary startle responses, many elongate species instead use a withdrawal movement. Studies of withdrawal have focused on the response to head-directed or nonspecific stimuli. During withdrawal, the animal moves its head back from the stimulus, often resulting in several tight bends in the body. In contrast to C-start or S-start behaviors, withdrawal to a head stimulus generally does not involve a subsequent propulsive stage of movement. We examined intraspecific diversity in withdrawal behavior and muscle activity patterns of the rope fish, Erpetoichthys calabaricus, in response to stimulation of the head and the tail. In addition, we describe the anatomy of the Mauthner cells and their axon caps, structures that are generally absent in species with a withdrawal startle. We recorded high-speed video (250 Hz)and electromyograms (EMGs) from 12 electrodes in the axial muscle during the behavioral response. We used Bodian silver staining techniques to visualize Mauthner cell and axon cap morphology. We found that E. calabaricus responds with a withdrawal to both head and tail stimulation. Tail stimulation elicits a stronger kinematic and muscle activity response than head stimulation. While withdrawal movement generally constitutes the entire response to head stimuli, withdrawal was followed by propulsive movements when the tail was stimulated, suggesting that withdrawal can both act alone and serve as the first stage of a propulsive startle. Unexpectedly, bilaterality of muscle activity was variable for responses to both head and tail stimuli. In addition, we were surprised to find that E. calabaricus has a distinct axon cap associated with its Mauthner cell. These data suggest that the withdrawal response is a more diverse functional system than has previously been believed.
Neuromuscular control of aerodynamic forces and moments in the blowfly,Calliphora vicina
Authors: Balint Claire N. , Dickinson Michael H.
Published: October 2004

Flies are among the most agile of flying insects, a capacity that ultimately results from their nervous system's control over steering muscles and aerodynamic forces during flight. In order to investigate the relationships among neuromuscular control, musculo-skeletal mechanics and flight forces, we captured high-speed, three-dimensional wing kinematics of the blowfly, Calliphora vicina, while simultaneously recording electromyogram signals from prominent steering muscles during visually induced turns. We used the quantified kinematics to calculate the translational and rotational components of aerodynamic forces and moments using a theoretical quasi-steady model of force generation, confirmed using a dynamically scaled mechanical model of a Calliphora wing. We identified three independently controlled features of the wingbeat trajectory –downstroke deviation, dorsal amplitude and mode. Modulation of each of these kinematic features corresponded to both activity in a distinct steering muscle group and a distinct manipulation of the aerodynamic force vector. This functional specificity resulted from the independent control of downstroke and upstroke forces rather than the independent control of separate aerodynamic mechanisms. The predicted contributions of each kinematic feature to body lift, thrust, roll, yaw and pitch are discussed.
Heart rate and energetics of free-ranging king penguins (Aptenodytes patagonicus)
Authors: Froget G. , Butler P. J. , Woakes A. J. , Fahlman A. , Kuntz G. , Le Maho Y. , Handrich Y.
Published: October 2004

The main objective of this study was to determine heart rate(fh) and the energetic costs of specific behaviours of king penguins while ashore and while foraging at sea during their breeding period. In particular, an estimate was made of the energetic cost of diving in order to determine the proportion of dives that may exceed the calculated aerobic dive limit (cADL; estimated usable O2 stores/estimated rate of oxygen consumption during diving).

An implanted data logger enabled fh and diving behaviour to be monitored from 10 free-ranging king penguins during their breeding period. Using previously determined calibration equations, it was possible to estimate rate of oxygen consumption(V̇O2) when the birds were ashore and during various phases of their foraging trips. Diving behaviour showed a clear diurnal pattern, with a mixture of deep (>40 m),long (>3 min) and shallow (<40 m), short (<3 min) dives from dawn to dusk and shallow, short dives at night. Heart rate during dive bouts and dive cycles (dive + post-dive interval) was 42% greater than that when the birds were ashore. During diving, fh was similar to the `ashore'value (87±4 beats min–1), but it did decline to 76% of the value recorded from king penguins resting in water. During the first hour after a diving bout, fh was significantly higher than the average value during diving (101±4 beats min–1) and for the remainder of the dive bout.

Rates of oxygen consumption estimated from these (and other) values of fh indicate that when at sea, metabolic rate (MR) was 83%greater than that when the birds were ashore [3.15 W kg–1(–0.71, +0.93), where the values in parentheses are the computed standard errors of the estimate], while during diving bouts and dive cycles,it was 73% greater than the `ashore' value. Although estimated MR during the total period between dive bouts was not significantly different from that during dive bouts [5.44 W kg–1 (–0.30, +0.32)], MR during the first hour following a dive bout was 52% greater than that during a diving bout. It is suggested that this large increase following diving(foraging) activity is, at least in part, the result of rewarming the body,which occurs at the end of a diving bout. From the measured behaviour and estimated values of V̇O2, it was evident that approximately 35% of the dives were in excess of the cADL. Even if V̇O2 during diving was assumed to be the same as when the birds were resting on water,approximately 20% of dives would exceed the cADL. As V̇O2 during diving is, in fact, that estimated for a complete dive cycle, it is quite feasible that V̇O2 during diving itself is less than that measured for birds resting in water. It is suggested that the regional hypothermia that has been recorded in this species during diving bouts may be at least a contributing factor to such hypometabolism.
Comparison of the cost of short flights in a nectarivorous and a non-nectarivorous bird
Authors: Hambly C. , Pinshow B. , Wiersma P. , Verhulst S. , Piertney S. B. , Harper E. J. , Speakman J. R.
Published: October 2004

Although most birds are accustomed to making short flights, particularly during foraging, the flight patterns during these short periods of activity differ between species. Nectarivorous birds, in particular, often spend time hovering, while non-nectarivorous birds do not. The cost of short flights is likely therefore to differ between nectarivorous and non-nectarivorous birds because of the different energetic contributions of different flight types to the behaviour. The 13C-labelled bicarbonate technique was used to measure the energy cost of short flights in the nectarivorous Palestine sunbird Nectarinia osea (mean mass 6.17±0.16 g, N=8)and the non-nectarivorous starling Sturnus vulgaris (mean mass 70.11±1.11 g, N=9). The technique was initially calibrated in five individuals for each species at temperatures ranging from 1 to 35°C,by comparing the isotope elimination rate to the metabolic rate measured simultaneously by indirect calorimetry. The cost for short intermittent flight was then measured by encouraging birds to fly between two perches at either end of a narrow corridor (perch distance for sunbirds, 6 m; for starlings, 5 m), and measuring the amount of isotope eliminated during the flight. The isotope elimination rate was interpolated onto the calibration equation to predict flight cost, as a direct calibration could not be performed during flight. Mean energy expenditure during flight was 1.64±0.32 W in sunbirds, while in starlings the flight costs averaged 20.6±0.78 W. Energy cost of flight relative to basal metabolic rate was substantially greater in the starling than the sunbird. Phylogenetic analysis of different modes of flight in these and additional species suggests that differences in flight behaviour may cause these elevated costs in slow flying non-nectarivores such as starlings, compared to birds that are more prone to short intermittent flights like the sunbirds.
The energy cost of loaded flight is substantially lower than expected due to alterations in flight kinematics
Authors: Hambly C. , Harper E. J. , Speakman J. R.
Published: October 2004

The effect of experimentally increased wing loading on the energy cost of flight was examined in cockatiels Nyphicus hollandicus. Five individuals were flown for periods of approximately 2 min, while carrying additional payload mass amounting to between 5 and 20% of unloaded body mass. The energy cost of flight was measured using the 13C-labelled bicarbonate technique, which was also calibrated in a separate experiment on resting birds, by comparing the elimination rate of 13C in breath with a simultaneous measurement of oxygen consumption by indirect calorimetry. It was not possible to perform a similar calibration during flight when energy costs were higher, so we extrapolated the relationship from the resting calibration to predict flight cost. Flight cost in the pre-manipulated individuals averaged 16.7±1.8 W. Flight cost in the pre-manipulated birds was significantly related to the interaction between downstroke duration and flight speed. There was no significant increase in flight cost with increases in payload mass. The birds responded to payload masses between 5 and 15% of their unloaded body mass by decreasing flight speed relative to unloaded birds, while maintaining wing beat frequency(Fb). At a payload mass equivalent to 20% of body mass,however, the birds flew at higher speeds than unloaded controls, and had a significantly higher Fb, generated by a reduction in both the upstroke and downstroke durations. Wing amplitude was unaffected by the increase in loading. Using the measured flight parameters, the effect of loading was not significantly different than predicted using aerodynamic models.