bluuebunny/crossref_metadata_2025 huggingface dataset:
Stem cell–specific epigenetic priming and B cell–specific transcriptional activation at the mouse Cd19 locus
Authors: Walter Korden , Bonifer Constanze , Tagoh Hiromi
Published: June 2008

Low-level expression of multiple lineage-specific genes is a hallmark of hematopoietic stem cells (HSCs). HSCs predominantly express genes specific for the myeloid or megakaryocytic-erythroid lineages, whereas the transcription of lymphoid specific genes appears to begin after lymphoid specification. It has been demonstrated for a number of genes that epigenetic priming occurs before gene expression and lineage specification; however, little is known about how epigenetic priming of lymphoid genes is regulated. To address the question of how B cell–restricted expression is established, we studied activation of the Cd19 gene during hematopoietic development. We identified a B cell–specific upstream enhancer and showed that the developmental regulation of Cd19 expression involves precisely coordinated alterations in transcription factor binding and chromatin remodeling at Cd19 cis-regulatory elements. In multipotent progenitor cells, Cd19 chromatin is first remodeled at the upstream enhancer, and this remodeling is associated with binding of E2A. This is followed by the binding of EBF and PAX5 during B-cell differentiation. The Cd19 promoter is transcriptionally activated only after PAX5 binding. Our experiments give important mechanistic insights into how widely expressed and B lineage–specific transcription factors cooperate to mediate the developmental regulation of lymphoid genes during hematopoiesis.
Lymphoid precursors are directed to produce dendritic cells as a result of TLR9 ligation during herpes infection
Authors: Welner Robert S. , Pelayo Rosana , Nagai Yoshinori , Garrett Karla P. , Wuest Todd R. , Carr Daniel J. , Borghesi Lisa A. , Farrar Michael A. , Kincade Paul W.
Published: June 2008

Hematopoietic stem and progenitor cells were previously found to express Toll-like receptors (TLRs), suggesting that bacterial/viral products may influence blood cell formation. We now show that common lymphoid progenitors (CLPs) from mice with active HSV-1 infection are biased to dendritic cell (DC) differentiation, and the phenomenon is largely TLR9 dependent. Similarly, CLPs from mice treated with the TLR9 ligand CpG ODN had little ability to generate CD19+ B lineage cells and had augmented competence to generate DCs. TNFα mediates the depletion of late-stage lymphoid progenitors from bone marrow in many inflammatory conditions, but redirection of lymphopoiesis occurred in TNFα−/− mice treated with CpG ODN. Increased numbers of DCs with a lymphoid past were identified in Ig gene recombination substrate reporter mice treated with CpG ODN. TLR9 is highly expressed on lymphoid progenitors, and culture studies revealed that those receptors, rather than inflammatory cytokines, accounted for the production of several types of functional DCs. Common myeloid progenitors are normally a good source of DCs, but this potential was reduced by TLR9 ligation. Thus, alternate differentiation pathways may be used to produce innate effector cells in health and disease.
Does the lipid-lowering peroxisome proliferator-activated receptors ligand bezafibrate prevent colon cancer in patients with coronary artery disease?
Authors: Tenenbaum Alexander , Boyko Valentina , Fisman Enrique Z , Goldenberg Ilan , Adler Yehuda , Feinberg Micha S , Motro Michael , Tanne David , Shemesh Joseph , Schwammenthal Ehud , Behar Solomon
Published: June 2008

Background

Epidemiologic studies have suggested that hypertriglyceridemia and insulin resistance are related to the development of colon cancer. Nuclear peroxisome proliferator-activated receptors (PPAR), which play a central role in lipid and glucose metabolism, had been hypothesized as being involved in colon cancerogenesis. In animal studies the lipid-lowering PPAR ligand bezafibrate suppressed colonic tumors. However, the effect of bezafibrate on colon cancer development in humans is unknown. Therefore, we proposed to investigate a possible preventive effect of bezafibrate on the development of colon cancer in patients with coronary artery disease during a 6-year follow-up.

Methods

Our population included 3011 patients without any cancer diagnosis who were enrolled in the randomized, double blind Bezafibrate Infarction Prevention (BIP) Study. The patients received either 400 mg of bezafibrate retard (1506 patients) or placebo (1505 patients) once a day. Cancer incidence data were obtained by matching a subject's identification numbers with the National Cancer Registry. Each matched record was checked for correct identification.

Results

Development of new cancer (all types) was recorded in 177 patients: in 79 (5.25%) patients from the bezafibrate group vs. 98 (6.51%) from the placebo group. Development of colon cancer was recorded in 25 patients: in 8 (0.53%) patients from the bezafibrate group vs. 17 (1.13%) from the placebo group, (Fisher's exact test: one side p = 0.05; two side p = 0.07).

A difference in the incidence of cancer was only detectable after a 4 year lag and progressively increased with continued follow-up. On multivariable analysis the colon cancer risk in patients who received bezafibrate tended to be lower with a hazard ratio of 0.47 and 95% confidence interval 0.2–1.1.

Conclusion

Our data, derived from patients with coronary artery disease, support the hypothesis regarding a possible preventive effect of bezafibrate on the development of colon cancer.
Mild therapeutic hypothermia shortens intensive care unit stay of survivors after out-of-hospital cardiac arrest compared to historical controls
Authors: Storm Christian , Steffen Ingo , Schefold Joerg C , Krueger Anne , Oppert Michael , Jörres Achim , Hasper Dietrich
Published: June 2008

Introduction

Persistent coma is a common finding after cardiac arrest and has profound ethical and economic implications. Evidence suggests that therapeutic hypothermia improves neurological outcome in these patients. In this analysis, we investigate whether therapeutic hypothermia influences the length of intensive care unit (ICU) stay and ventilator time in patients surviving out-of-hospital cardiac arrest.

Methods

A prospective observational study with historical controls was conducted at our medical ICU. Fifty-two consecutive patients (median age 62.6 years, 43 males, 34 ventricular fibrillation) submitted to therapeutic hypothermia after out-of-hospital cardiac arrest were included. They were compared with a historical cohort (n = 74, median age 63.8 years, 53 males, 43 ventricular fibrillation) treated in the era prior to hypothermia treatment. All patients received the same standard of care. Neurological outcome was assessed using the Pittsburgh cerebral performance category (CPC) score. Univariate analyses and multiple regression models were used.

Results

In survivors, therapeutic hypothermia and baseline disease severity (Acute Physiology and Chronic Health Evaluation II [APACHE II] score) were both found to significantly influence ICU stay and ventilator time (all P < 0.01). ICU stay was shorter in survivors receiving therapeutic hypothermia (median 14 days [interquartile range (IQR) 8 to 26] versus 21 days [IQR 15 to 30] in the control group; P = 0.017). ICU length of stay and time on ventilator were prolonged in patients with CPC 3 or 4 compared with patients with CPC 1 or 2 (P = 0.003 and P = 0.034, respectively). Kaplan-Meier analysis showed improved probability for 1-year survival in the hypothermia group compared with the controls (log-rank test P = 0.013).

Conclusion

Therapeutic hypothermia was found to significantly shorten ICU stay and time of mechanical ventilation in survivors after out-of-hospital cardiac arrest. Moreover, profound improvements in both neurological outcome and 1-year survival were observed.
Identification of transcripts with enriched expression in the developing and adult pancreas
Authors: Hoffman Brad G , Zavaglia Bogard , Witzsche Joy , Ruiz de Algara Teresa , Beach Mike , Hoodless Pamela A , Jones Steven JM , Marra Marco A , Helgason Cheryl D
Published: June 2008

Background

Despite recent advances, the transcriptional hierarchy driving pancreas organogenesis remains largely unknown, in part due to the paucity of comprehensive analyses. To address this deficit we generated ten SAGE libraries from the developing murine pancreas spanning Theiler stages 17-26, making use of available Pdx1 enhanced green fluorescent protein (EGFP) and Neurog3 EGFP reporter strains, as well as tissue from adult islets and ducts.

Results

We used a specificity metric to identify 2,536 tags with pancreas-enriched expression compared to 195 other mouse SAGE libraries. We subsequently grouped co-expressed transcripts with differential expression during pancreas development using K-means clustering. We validated the clusters first using quantitative real time PCR and then by analyzing the Theiler stage 22 pancreas in situ hybridization staining patterns of over 600 of the identified genes using the GenePaint database. These were then categorized into one of the five expression domains within the developing pancreas. Based on these results we identified a cascade of transcriptional regulators expressed in the endocrine pancreas lineage and, from this, we developed a predictive regulatory network describing beta-cell development.

Conclusion

Taken together, this work provides evidence that the SAGE libraries generated here are a valuable resource for continuing to elucidate the molecular mechanisms regulating pancreas development. Furthermore, our studies provide a comprehensive analysis of pancreas development, and insights into the regulatory networks driving this process are revealed.
The intricate interface between immune and metabolic regulation: a role for leptin in the pathogenesis of multiple sclerosis?
Authors: Matarese Giuseppe , Procaccini Claudio , De Rosa Veronica
Published: June 2008

Over the last few years, a series of molecules known to play a function in metabolism has also been shown to play an important role in the regulation of the immune response. In this context, the adipocyte-derived hormone leptin has been shown to regulate the immune response in normal as well as in pathological conditions. More specifically, it has been shown that conditions of reduced leptin production (i.e., genetic leptin deficiency, anorexia nervosa, malnutrition) are associated with increased susceptibility to infections. Conversely, immune-mediated disorders such as autoimmune disorders are associated with increased secretion of leptin and production of proinflammatory, pathogenic cytokines. Leptin could represent the “missing link” among immune response, metabolic function, and nutritional status. Indeed, more recently, leptin-deficient mice have been shown to be resistant to a series of experimentally induced autoimmune disorders including experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Normal wild-type mice show increased secretion of leptin in serum upon EAE induction, and brain inflammatory infiltrates stain positive for leptin. Finally, leptin neutralization with leptin antagonists improves the EAE course by profoundly altering intracellular signaling of myelin-reactive T cells and increasing the number of regulatory forkhead/winged helix transcription factor 3+CD4+ T cells. These data suggest that leptin can be considered as a link among immune tolerance, metabolic state, and autoimmunity and that strategies aimed at interfering with the leptin axis could represent innovative, therapeutic tools for autoimmune disorders.
Differential cell fates induced by all-trans retinoic acid-treated HL-60 human leukemia cells
Authors: Ozeki Munetaka , Shively John E
Published: June 2008

HL-60 human leukemia cells, differentiated into a neutrophil lineage by all-trans retinoic acid (ATRA) treatment, express three members of the carcinoembryonic antigen (CEA) gene family, CEA-related cell adhesion molecule 1 (CEACAM1; CD66a), CEACAM3 (CD66d), and CEACAM6 (CD66c). CD66d is a neutrophil lineage-specific marker, and CD66a and CD66c are found on epithelial and other cells. HL-60 cells continuously treated with ATRA underwent apoptosis, and cells transiently treated for 1 day underwent cell-cycle arrest, entered into senescence, and exhibited reduced apoptosis with CD66-positive cells accounting for the majority of live cells. CD66 antigens were also induced in NB4 leukemic cells upon continuous treatment with ATRA. NB4 cells underwent apoptosis with a higher frequency in transient versus continuous-treated cells (38% vs. 19% at Day 5), in contrast to HL-60 cells that underwent cell-cycle arrest and senescence when transiently treated with ATRA. CD66 antigens were not induced in transient, ATRA-treated NB4 cells compared with HL-60 cells. Cell-cycle arrest in HL-60 cells involved reduction in expression levels of p21, cyclins D and E, while Rb1 exhibited reduction in protein levels without changes in mRNA levels over the time course of ATRA treatment. Analysis of several proapoptotic proteins implicated the activation of calpain and cleavage of Bax in the intrinsic apoptotic pathway, similar to published studies about the apoptosis of neutrophils. CD1d expression was also induced by ATRA in HL-60 cells and ligation with anti-CD1d antibody-induced apoptosis. In contrast, CD1d-positive primary monocytes were protected from spontaneous apoptosis by CD1d ligation. These studies demonstrate distinct cell fates for ATRA-treated HL-60 cells that provide new insights into ATRA-induced cell differentiation.
Induction of IL-33 expression and activity in central nervous system glia
Authors: Hudson Chad A , Christophi George P , Gruber Ross C , Wilmore Joel R , Lawrence David A , Massa Paul T
Published: June 2008

IL-33 is a novel member of the IL-1 cytokine family and a potent inducer of type 2 immunity, as mast cells and Th2 CD4+ T cells respond to IL-33 with the induction of type 2 cytokines such as IL-13. IL-33 mRNA levels are extremely high in the CNS, and CNS glia possess both subunits of the IL-33R, yet whether IL-33 is produced by and affects CNS glia has not been studied. Here, we demonstrate that pathogen-associated molecular patterns (PAMPs) significantly increase IL-33 mRNA and protein expression in CNS glia. Interestingly, IL-33 was localized to the nucleus of astrocytes. Further, CNS glial and astrocyte-enriched cultures treated with a PAMP followed by an ATP pulse had significantly higher levels of supernatant IL-1β and IL-33 than cultures receiving any single treatment (PAMP or ATP). Supernatants from PAMP + ATP-treated glia induced the secretion of IL-6, IL-13, and MCP-1 from the MC/9 mast cell line in a manner similar to exogenous recombinant IL-33. Further, IL-33 levels and activity were increased in the brains of mice infected with the neurotropic virus Theiler’s murine encephalomyelitis virus. IL-33 also had direct effects on CNS glia, as IL-33 induced various innate immune effectors in CNS glia, and this induction was greatly amplified by IL-33-stimulated mast cells. In conclusion, these results implicate IL-33-producing astrocytes as a potentially critical regulator of innate immune responses in the CNS.
Clinical Phenotype of Muscle‐specific Tyrosine Kinase‐antibody‐positive Myasthenia Gravis
Authors: Wolfe Gil I. , Oh Shin J.
Published: June 2008

Antibodies to muscle‐specific receptor tyrosine kinase (MuSK‐Ab) are detected in approximately 40% of generalized acetylcholine receptor (AChR) antibody‐negative myasthenia gravis (MG). Based on a growing number of clinical series, a MuSK‐Ab‐positive phenotype is emerging. While these clinical patterns are not wholly distinct from either AChR‐Ab‐positive or seronegative (both AChR‐Ab and MuSK‐Ab‐negative) MG, they are still helpful in identifying these patients. MuSK‐Ab‐positive MG patients are predominantly female with more prominent cranial and bulbar involvement and more frequent crises than other MG populations. Disease onset tends to be earlier, generally by the third or fourth decade. MuSK‐Ab‐positive patients are more likely to display poor tolerance of or a lack of improvement with anticholinesterase agents. The yield of repetitive nerve stimulation with conventional limb muscles is lower in these patients, but at least three‐quarters demonstrate abnormalities on recording of facial‐innervated muscles. Similarly, single‐fiber electromyography of distal limb muscles tends to have a lower yield of abnormality in MuSK‐Ab‐positive patients than either AChR‐Ab‐positive or seronegative MG, whereas jitter is increased in nearly all MuSK‐positive patients when proximal limb or cranial musculature is studied.
Extended Transcervical Thymectomy in the Treatment of Myasthenia Gravis
Authors: Khicha Sanjay G. , Kaiser Larry R. , Shrager Joseph B.
Published: June 2008

The ideal operative technique for thymectomy in myasthenia gravis remains controversial. Most surgeons perform thymectomy via median sternotomy, some supplementing this with an even more extensive mediastinal and cervical dissection designed to remove all areas of possible ectopic thymic tissue. We and others have advocated a transcervical approach that is less morbid and costly than sternotomy approaches. The transcervical approach allows a complete extracapsular thymic resection, but it does not address all areas of potential ectopic thymic tissue. We have published our experience with 151 extended transcervical thymectomies (TCT). At mean follow‐up of 53 months (complete follow‐up in 97%), Kaplan–Meier estimates of complete stable remission were 33% and 35% at 3 and 6 years. If one includes patients who became asymptomatic but remained on low dose, single‐drug immunosuppression as complete remissions (CRs), then the CR rates were 43% and 45% at 3 and 6 years. Longer term (mean 83 months) follow‐up of the earliest 84 patients in the series showed preserved CR rates. On multivariate analysis, only preoperative Osserman Class (group mean 2.3) was significantly associated with improved CR rate. These results were obtained with a major operative complication rate of 0.7% and minor complication rate of 6.6%, and nearly every operation was performed without the need for overnight hospital admission. We believe that these response rates following TCT are sufficiently similar to those following transsternal techniques of thymectomy to allow us to recommend this less morbid and less costly operation as an eminently reasonable choice in the surgical treatment of myasthenia gravis.
Genetic Factors in Autoimmune Myasthenia Gravis
Authors: Giraud Matthieu , Vandiedonck Claire , Garchon Henri‐Jean
Published: June 2008

Autoimmune myasthenia gravis (MG) is a multifactorial disease, markedly influenced by genetic factors, even though it shows limited heritability. The clinically typical form of autoimmune MG with thymus hyperplasia shows the most reproducible genetic associations, especially with the A1‐B8‐DR3 (8.1) haplotype of the major histocompatibility complex (MHC). However, because of strong linkage disequilibrium, the causative polymorphism in this region is not known yet. Increasing the density of genetic markers has nevertheless recently revealed the complex, but highly significant contribution of this essential genetic region in controlling the disease phenotype and the quantitative expression of serum autoantibodies. The advances of the human genome program, the development of genotyping and sequencing tools with increasing throughput, and the availability of powerful statistical methods now make feasible the dissection of a complex genetic region, such as the MHC and beyond, the systematic search throughout the genome for variants influencing disease predisposition. The identification of such functional variants should provide new clues to the pathogenesis of MG, as recently illustrated by the study of a promoter polymorphism of the CHRNA1 locus, influencing its thymic expression and central tolerance, or of a coding variant of the PTPN22 intracellular phosphatase.
Gonadotropin-Releasing Hormone in Third Ventricular Cerebrospinal Fluid: Endogenous Distribution and Exogenous Uptake
Authors: Caraty Alain , Skinner Donal C.
Published: June 2008

GnRH is detectable in the cerebrospinal fluid (CSF), but its source remains unidentified. Previous studies have harvested CSF for GnRH analysis from the median eminence region, but it is unknown whether GnRH in CSF is restricted to this region. If CSF-GnRH plays a physiological role, through volume transmission, to communicate with brain regions that express GnRH receptors but are not evidently innervated by GnRH neurons, then it is essential to establish whether GnRH is more pervasive throughout the cerebroventricular system. Three cannulae were placed in the supraoptic, infundibular, and pineal recesses of the third ventricle. GnRH was undetectable in lateral ventricle CSF. GnRH pulses were detected in all ewes in infundibular recess CSF, but at sites more rostral (supraoptic) and caudal (pineal), GnRH pulse frequency and amplitude significantly (P < 0.05) decreased. A GnRH surge was evident in CSF collected simultaneously from all cannulae, but the amplitude was greatest (P < 0.05) at the infundibular recess. A final study established whether iv administered GnRH enters the CSF. A 250-ng GnRH dose did not affect CSF-GnRH concentrations (1.6 ± 0.3 pg/ml), but 2.5 μg (2.7 ± 0.2 pg/ml; P < 0.001) and 1 mg (38.5 ± 10.6 pg/ml; P < 0.05) significantly increased CSF-GnRH concentrations. The present study shows: 1) the median eminence region is likely to be the major, if not only, source of GnRH entering the cerebroventricular system; and 2) exogenous GnRH crosses the blood-brain barrier, but extremely high doses are required to elevate CSF concentrations to physiological levels. Thus, CSF-GnRH may affect sites that are closer in proximity to the infundibular recess region than previously thought.
Effects of exogenous thyroid hormones on visual pigment composition in coho salmon (Oncorhynchus kisutch)
Authors: Temple Shelby E. , Ramsden Samuel D. , Haimberger Theodore J. , Veldhoen Kathy M. , Veldhoen Nik J. , Carter Nicolette L. , Roth Wolff-Michael , Hawryshyn Craig W.
Published: June 2008

The role of exogenous thyroid hormone on visual pigment content of rod and cone photoreceptors was investigated in coho salmon (Oncorhynchus kisutch). Coho vary the ratio of vitamin A1- and A2-based visual pigments in their eyes. This variability potentially alters spectral sensitivity and thermal stability of the visual pigments. We tested whether the direction of shift in the vitamin A1/A2 ratio, resulting from application of exogenous thyroid hormone, varied in fish of different ages and held under different environmental conditions. Changes in the vitamin A1/A2visual pigment ratio were estimated by measuring the change in maximum absorbance (λmax) of rods using microspectrophotometry(MSP). Exogenous thyroid hormone resulted in a long-wavelength shift in rod,middle-wavelength-sensitive (MWS) and long-wavelength-sensitive (LWS) cone photoreceptors. Rod and LWS cone λmax values increased,consistent with an increase in vitamin A2. MWS coneλ max values increased more than predicted for a change in the vitamin A1/A2 ratio. To account for this shift, we tested for the expression of multiple RH2 opsin subtypes. We isolated and sequenced a novel RH2 opsin subtype, which had 48 amino acid differences from the previously sequenced coho RH2 opsin. A substitution of glutamate for glutamine at position 122 could partially account for the greater than predicted shift in MWS cone λmax values. Our findings fit the hypothesis that a variable vitamin A1/A2 ratio provides seasonality in spectral tuning and/or improved thermal stability of visual pigments in the face of seasonal environmental changes, and that multiple RH2 opsin subtypes can provide flexibility in spectral tuning associated with migration–metamorphic events.
Detection of patches of coloured discs by bees
Authors: Wertlen Anna M. , Niggebrügge Claudia , Vorobyev Misha , Hempel de Ibarra Natalie
Published: June 2008

To find out how grouping of flowers into patches improves their detectability by hymenopteran pollinators, we trained honeybees and bumblebees to detect groups of three spatially separated disks and compared results with the detection limit for single disks. When the discs presented contrast to the long-wavelength-sensitive (L) receptor, grouping of disks improved the detectability. The disks were optically resolvable for the honeybee eye. The improvement of detectability was stronger for bumblebees than for honeybees. When disks did not present contrast to the L-receptor, the grouping did not improve the detectability, i.e. the detection limit was set by the size of a single disk. We conclude that in bees the neural mechanisms that improve detectability of grouped elements require input from the L-receptor. Our results indicate that grouping of flowers into sparse patches can improve their detectability by bees, even when individual flowers can be optically resolved by the eyes of bees, as long as flowers can be detected by the long-wavelength-sensitive receptor.
The responses of Atlantic cod (Gadus morhua L.) to ultrasound-emitting predators: stress, behavioural changes or debilitation?
Authors: Schack Henriette B. , Malte Hans , Madsen Peter T.
Published: June 2008

A previous study has reported that Atlantic cod can be conditioned to detect ultrasonic sound pulses of high intensity. This capability has been proposed as a mean for detection and avoidance of echolocating toothed whales that emit intense ultrasonic clicks. In this study, we use acoustic playbacks to test the hypotheses that unconditioned cod can detect and respond to intense ultrasound from toothed whales and from echosounders. Intense ultrasound exposure of 210 dB re. 1μPa (pp) did not cause a short-term stress response in the form of bradycardia in unconditioned cod. Free-swimming cod exposed to ultrasonic clicks and echosounder pulses with received levels of more than 204 dB re. 1 μPa (pp) did not elicit flight responses as seen in ultrasound detecting Alosinae. Furthermore, we tested the debilitating effects of high intensity ultrasound on swimming cod with no detected changes in swimming ability when exposed to more than 213 dB re. 1 μPa (pp). It is concluded that intense ultrasound exposure induces neither an antipredator nor a stress response in Atlantic cod, and that echosounder pulses and biosonar clicks therefore most probably play no ecophysiological role in wild cod populations.
A novel inwardly rectifying K+ channel, Kir2.5, is upregulated under chronic cold stress in fish cardiac myocytes
Authors: Hassinen Minna , Paajanen Vesa , Vornanen Matti
Published: June 2008

A new member of the inward-rectifier K+ channel subfamily Kir2 was isolated and characterised from the crucian carp (Carassius carassius) heart. When expressed in COS-1 cells this 422 amino acid protein produced an inward-rectifying channel with distinct single-channel conductance, mean open time and open probability. Phylogenetic sequence comparisons indicate that it is not homologous to any known vertebrate Kir channel, yet belongs to the Kir2 subfamily. This novel crucian carp channel increases the number of vertebrate Kir2 channels to five, and has therefore been designated as ccKir2.5 (cc for Carassius carassius). In addition to the ccKir2.5 channel, the ccKir2.2 and ccKir2.1 channels were expressed in the crucian carp heart, ccKir2.1 being present only in trace amounts (<0.8%of all Kir2 transcripts). Whole-cell patch clamp in COS-1 cells demonstrated that ccKir2.5 is a stronger rectifier than ccKir2.2 or ccKir2.1, and therefore passes weakly outward current. Single-channel conductance, mean open time and open probability of ccKir2.5 were, respectively, 1.6, 4.96 and 4.17 times as large as that of ccKir2.2. ccKir2.5 was abundantly expressed in atrium and ventricle of the heart and in skeletal muscle, but was a minor component of Kir2 in brain, liver, gill and kidney. Noticeably, ccKir2.5 was strongly responsive to chronic cold exposure. In fish reared at 4°C for 4 weeks,ccKir2.5 mRNA formed 59.1±2.1% and 65.6±3.2% of all ccKir2 transcripts in atrium and ventricle, respectively, while in fish maintained at 18°C the corresponding transcript levels were only 16.2±1.7% and 23.3±1.7%. The increased expression of ccKir2.5 at 4°C occurred at the expense of ccKir2.2, which was the main Kir2 isoform in 18°C acclimated fish. A cold-induced increase in the slope conductance of the ventricular IK1 from 707±49 to 1001±59 pS pF–1 (P<0.05) was thus associated with an isoform shift from ccKir2.2 towards ccKir2.5, suggesting that ccKir2.5 is a cold-adapted and ccKir2.2 a warm-adapted isoform of the inward-rectifying K+ channel.
The morphology and mechanical sensitivity of lateral line receptors in zebrafish larvae (Danio rerio)
Authors: Van Trump William J. , McHenry Matthew J.
Published: June 2008

The lateral line system of fish and amphibians detects water flow with receptors on the surface of the body. Although differences in the shape of these receptors, called neuromasts, are known to influence their mechanics, it is unclear how neuromast morphology affects the sensitivity of the lateral line system. We examined the functional consequences of morphological variation by measuring the dimensions of superficial neuromasts in zebrafish larvae (Danio rerio) and mathematically modeling their mechanics. These measurements used a novel morphometric technique that recorded landmarks in three dimensions at a microscopic scale. The mathematical model predicted mechanical sensitivity as the ratio of neuromast deflection to flow velocity for a range of stimulus frequencies. These predictions suggest that variation in morphology within this species generates a greater than 30-fold range in the amplitude of sensitivity and more than a 200-fold range of variation in cut-off frequency. Most of this variation was generated by differences in neuromast height that do not correlate with body position. Our results suggest that natural variation in cupular height within a species is capable of generating large differences in their mechanical filtering and dynamic range.
Propulsion performance of a skeleton-strengthened fin
Authors: Zhu Qiang , Shoele Kourosh
Published: June 2008

We examine numerically the performance of a thin foil reinforced by embedded rays resembling the caudal fins of many fishes. In our study, the supporting rays are depicted as nonlinear Euler–Bernoulli beams with three-dimensional deformability. This structural model is then incorporated into a boundary-element hydrodynamic model to achieve coupled fluid–structure interaction simulation. Kinematically, we incorporate both a homocercal mode with dorso-ventral symmetry and a heterocercal mode with dorso-ventral asymmetry. Using the homocercal mode, our results demonstrate that the anisotropic deformability of the ray-reinforced fin significantly increases its capacity of force generation. This performance enhancement manifests as increased propulsion efficiency, reduced transverse force and reduced sensitivity to kinematic parameters. Further reduction in transverse force is observed by using the heterocercal mode. In the heterocercal model, the fin also generates a small lifting force, which may be important in vertical maneuvers. Via three-dimensional flow visualization, a chain of vortex rings is observed in the wake. Detailed features of the wake, e.g. the orientation of the vortex rings in the heterocercal mode, agree with predictions based upon particle image velocimetry (PIV) measurements of flow around live fish.
Expression of myogenic regulatory factors in the muscle-derived electric organ ofSternopygus macrurus
Authors: Kim Jung A. , Laney Christine , Curry Jeanne , Unguez Graciela A.
Published: June 2008

In most groups of electric fish, the current-producing cells of electric organs (EOs) derive from striated muscle fibers but retain some phenotypic characteristics of their precursor muscle cells. Given the role of the MyoD family of myogenic regulatory factors (MRFs) in the transcriptional activation of the muscle program in vertebrates, we examined their expression in the electrocytes of the gymnotiform Sternopygus macrurus. We estimated the number of MRF genes in the S. macrurus genome and our Southern blot analyses revealed a single MyoD, myogenin, myf5 and MRF4 gene. Quantitative RT-PCR showed that muscle and EO transcribe all MRF genes. With the exception of MyoD, the endogenous levels of myogenin, myf5 and MRF4 transcripts in electrocytes were greater than those detected in muscle fibers. These data indicate that MRF expression levels are not sufficient to predict the level to which the muscle program is manifested. Qualitative expression analysis of MRF co-regulators MEF2C, Id1 and Id2 also revealed these genes not to be unique to either muscle or EO, and detected similar expression patterns in the two tissues. Therefore, the partial muscle program of the EO is not associated with a partial expression of MRFs or with apparent distinct levels of some MRF co-factors. In addition, electrical inactivation by spinal cord transection(ST) resulted in the up-regulation of some muscle proteins in electrocytes without an accompanying increase in MRF transcript levels or notable changes in the co-factors MEF2C, Id1 and Id2. These findings suggest that the neural regulation of the skeletal muscle program via MRFs in S. macrurus might differ from that of their mammalian counterparts. Together, these data further our understanding of the molecular processes involved in the plasticity of the vertebrate skeletal muscle program that brings about the muscle-like phenotype of the non-contractile electrogenic cells in S. macrurus.
Vocal fold elasticity of the Rocky Mountain elk (Cervus elaphus nelsoni) – producing high fundamental frequency vocalization with a very long vocal fold
Authors: Riede Tobias , Titze Ingo R.
Published: June 2008

The vocal folds of male Rocky Mountain elk (Cervus elaphus nelsoni) are about 3 cm long. If fundamental frequency were to be predicted by a simple vibrating string formula, as is often done for the human larynx, such long vocal folds would bear enormous stress to produce the species-specific mating call with an average fundamental frequency of 1 kHz. Predictions would be closer to 50 Hz. Vocal fold histology revealed the presence of a large vocal ligament between the vocal fold epithelium and the thyroarytenoid muscle. In tensile tests, the stress–strain response of vocal fold epithelium and the vocal ligament were determined. Elasticity of both tissue structures reached quantitative values similar to human tissue. It seems unlikely that the longitudinal stress in elk vocal folds can exceed that in human vocal folds by an order of magnitude to overcome the drop in fundamental frequency due to a 3:1 increase in vocal fold length. Alternative hypotheses of how the elk produces high fundamental frequency utterances,despite its very long vocal fold, include a reduced effective vocal fold length in vibration, either due to bending properties along the vocal fold, or by actively moving the boundary point with muscle stiffening. The relationships between an individual's average fundamental frequency, vocal fold length and body size are discussed.
Scallops visually respond to the size and speed of virtual particles
Authors: Speiser Daniel I. , Johnsen Sönke
Published: June 2008

The unique eyes of scallops are abundant along the right and left valve mantle margins. These eyes form images by reflection off a concave spherical mirror, and give scallops an angular resolution of around 2°, far better than the 13–40° angular resolution provided by the eyes of other bivalves. It has been argued that bivalve mantle eyes primarily act as predator detectors, but behavioral studies have suggested that vision may serve additional purposes in scallops. By placing specimens of the bay scallop Argopecten irradians (Lamarck 1819) in a tank with 5–10 cm s–1 flow, showing them simulated images of moving particles,and recording their behavior, we tested whether visual cues may influence feeding behavior in these animals. We found that scallops opened their anterior mantle gapes significantly more often when they were shown 1.5×1.5 mm virtual particles (with angular sizes of 3.4°) than when they were shown 0.6×0.6 mm particles (1.4°; P<0.001) or no particles at all (P<0.05). We also found that scallops opened their anterior mantle gapes significantly more often when they were shown virtual particles moving at 2.5 cm s–1 (P<0.01)or 5 cm s–1 (P<0.05) than when they were shown particles moving at 10 cm s–1. Because scallops must open their anterior mantle gapes to feed, our findings suggest that these animals may visually detect the size and speed of moving particles and use this information to help identify favorable feeding conditions.
Cell-mediated immune activation rapidly decreases plasma carotenoids but does not affect oxidative stress in red-legged partridges (Alectoris rufa)
Authors: Perez-Rodriguez Lorenzo , Mougeot François , Alonso-Alvarez Carlos , Blas Julio , Viñuela Javier , Bortolotti Gary R.
Published: June 2008

In animals yellow-orange-red sexual traits pigmented by carotenoids have been suggested to act as signals of current health. Because carotenoids have important physiological functions, individuals might trade-off allocating these pigments to self-maintenance versus coloration. Carotenoids may act as scavengers of free radicals that are released during an immune response. Here, we experimentally assessed whether a local cell-mediated immune response affects circulating carotenoids, antioxidant status, oxidative damage and the expression of a carotenoid-based trait. Male red-legged partridges (Alectoris rufa) were subcutaneously injected with phytohaemagglutinin (PHA) or with phosphate buffer solution (controls). The effect of the treatment on circulating carotenoids, total plasma antioxidant status (TAS), lipid oxidative damage in erythrocytes (TBARS) and ornamentation was assessed. Immune challenge induced a 13% decrease in circulating carotenoids within 24 h. However, this treatment did not affect TAS, TBARS or coloration. Coloration, circulating carotenoids and cell-mediated immune response were positively correlated, but these were not related to TAS or TBARS. Carotenoids were only weakly related to TAS after controlling for the effect of uric acid levels. These results suggest that carotenoid-based ornaments may honestly indicate immunocompetence but probably not antioxidant capacity in this species, and that carotenoids might be relatively weak antioxidants in the plasma. Furthermore, even a relatively harmless and locally elicited immune challenge had important effects on circulating carotenoids, but this effect did not appear to be associated with oxidative stress. Alternative mechanisms linking carotenoids to immunity (not necessarily relying on the use of these pigments as antioxidants) should be considered in future studies on birds.
Multimodal signaling in fowl,Gallus gallus
Authors: Smith Carolynn L. , Evans Christopher S.
Published: June 2008

Many social birds produce food-associated calls. In galliforms, these vocalizations are typically accompanied by a distinctive visual display,creating a multimodal signal known as tidbitting. This system is ideal for experimental analysis of the way in which signal components interact to determine overall efficacy. We used high-definition video playback to explore perception of male tidbitting by female fowl, Gallus gallus. Hens experienced four treatments consisting of multimodal tidbitting, visual tidbitting without sound, audible tidbitting without a male present, and a silent empty cage control. Hens took longer to begin food search when the display was silent, but the overall rate of this response did not differ among the multimodal, visual only or audio only playback treatments. These results suggest that the visual and vocal components of tidbitting are redundant, but they also highlight the importance of a temporal dimension for any categorization scheme. Visual displays also evoked inspection behavior,characterized by close binocular fixation on the head of the playback male,which is known to facilitate individual recognition. This may also allow hens to assess male quality. Such social responses reveal that tidbitting probably has multiple functions and provide a new insight into the selective factors responsible for the evolution of this complex multimodal signal.
Why go bipedal? Locomotion and morphology in Australian agamid lizards
Authors: Clemente Christofer J. , Withers Philip C. , Thompson Graham , Lloyd David
Published: June 2008

Bipedal locomotion by lizards has previously been considered to provide a locomotory advantage. We examined this premise for a group of quadrupedal Australian agamid lizards, which vary in the extent to which they will become bipedal. The percentage of strides that each species ran bipedally, recorded using high speed video cameras, was positively related to body size and the proximity of the body centre of mass to the hip, and negatively related to running endurance. Speed was not higher for bipedal strides, compared with quadrupedal strides, in any of the four species, but acceleration during bipedal strides was significantly higher in three of four species. Furthermore, a distinct threshold between quadrupedal and bipedal strides, was more evident for acceleration than speed, with a threshold in acceleration above which strides became bipedal. We calculated these thresholds using probit analysis, and compared these to the predicted threshold based on the model of Aerts et al. Although there was a general agreement in order, the acceleration thresholds for lizards were often lower than that predicted by the model. We suggest that bipedalism, in Australian agamid lizards, may have evolved as a simple consequence of acceleration, and does not confer any locomotory advantage for increasing speed or endurance. However, both behavioural and threshold data suggest that some lizards actively attempt to run bipedally, implying some unknown advantage to bipedal locomotion.
Front leg movements and tibial motoneurons underlying auditory steering in the cricket (Gryllus bimaculatusdeGeer)
Authors: Baden T. , Hedwig B.
Published: June 2008

Front leg movements in the cricket (Gryllus bimaculatus) were measured during phonotactic steering on a trackball together with electromyogram recordings of the tibial extensor and flexor muscles. Up–down leg movements clearly indicated the step cycle and were independent of auditory stimulation. By contrast, left–right movements of the front leg were dependent on sound direction, with crickets performing rapid steering leg movements towards the active speaker. Steering movements were dependent on the phase of sound relative to the step cycle, and were greatest for sounds occurring during the swing phase. During phonotaxis the slow extensor tibiae motoneuron responded to ipsilateral sounds with a latency of 35–40 ms, whereas the fast flexor tibiae motoneurons were excited by contralateral sound. We made intracellular recordings of two tibial extensor and at least eight flexor motoneurons. The fast extensor tibiae, the slow extensor tibiae and one fast flexor tibiae motoneurons were individually identifiable, but a group of at least four fast flexor tibiae as well as at least three slow flexor tibiae motoneurons of highly similar morphology could not be distinguished. Motoneurons received descending inputs from cephalic ganglia and from local prothoracic networks. There was no overlap between the dendritic fields of the tibial motoneurons and the auditory neuropile. They did not respond to auditory stimulation at rest. Neither extracellular stimulation of descending pathways nor pharmacological activation of prothoracic motor networks changed the auditory responsiveness. Therefore, any auditory input to tibial motoneurons is likely to be indirect, possibly via the brain.
Cold rearing improves cold-flight performance inDrosophila viachanges in wing morphology
Authors: Frazier Melanie R. , Harrison Jon F. , Kirkton Scott D. , Roberts Stephen P.
Published: June 2008

We use a factorial experimental design to test whether rearing at colder temperatures shifts the lower thermal envelope for flight of Drosophila melanogaster Meigen to colder temperatures. D. melanogaster that developed in colder temperatures (15°C) had a significant flight advantage in cold air compared to flies that developed in warmer temperatures(28°C). At 14°C, cold-reared flies failed to perform a take-off flight∼47% of the time whereas warm-reared flies failed ∼94% of the time. At 18°C, cold- and warm-reared flies performed equally well. We also compared several traits in cold- and warm-developing flies to determine if cold-developing flies had better flight performance at cold temperatures due to changes in body mass, wing length, wing loading, relative flight muscle mass or wing-beat frequency. The improved ability to fly at low temperatures was associated with a dramatic increase in wing area and an increase in wing length (after controlling for wing area). Flies that developed at 15°C had∼25% more wing area than similarly sized flies that developed at 28°C. Cold-reared flies had slower wing-beat frequencies than similarly sized flies from warmer developmental environments, whereas other traits did not vary with developmental temperature. These results demonstrate that developmental plasticity in wing dimensions contributes to the improved flight performance of D. melanogaster at cold temperatures, and ultimately, may help D. melanogaster live in a wide range of thermal environments.
Combustion structure of free and wall-impinging diesel jets by simultaneous laser-induced fluorescence of formaldehyde, poly-aromatic hydrocarbons, and hydroxides
Authors: Bruneaux G
Published: June 2008

The structure of combusting diesel jets in low-temperature conditions is studied using laser-induced fluorescence (LIF). A single-hole common rail diesel injector is used, which allows high injection pressures up to 120 MPa. Visualizations are performed in a high-pressure, high-temperature cell that is designed to reproduce the typical thermodynamic conditions in the combustion chamber of a diesel engine. Planar LIF of the hydroxide (OH) radicals (OH LIF) with excitation near 280 nm and LIF with excitation at 355 nm (355 LIF) are applied simultaneously. In addition, simultaneous 355 LIF imaging and spatially resolved single-shot spectral analysis are performed in order to identify spatially the contribution of formaldehyde and poly-aromatic hydrocarbon (PAH) fluorescence in the 355 LIF images. Also, the analysis of the pressure signal in the chamber and subsequent calculation of heat release rates are used to locate temporally each image within the different combustion stages. The combustion structure of a low-temperature freely propagating jet during those stages is then analysed in detail, using the information given by the simultaneous LIF techniques on the different reaction zones; this is then summarized by a conceptual model. Finally, the simultaneous LIF techniques are applied to a configuration where a jet impinges on a perpendicular wall. The results are used to analyse the effect of wall interaction on the combustion structure.