bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuromedin S Is a Novel Anorexigenic Hormone
Authors: Ida Takanori , Mori Kenji , Miyazato Mikiya , Egi Yutaka , Abe Shinsuke , Nakahara Keiko , Nishihara Masugi , Kangawa Kenji , Murakami Noboru
Published: June 2005

A novel 36-amino acid neuropeptide, neuromedin S (NMS), has recently been identified in rat brain and has been shown to be an endogenous ligand for two orphan G protein-coupled receptors, FM-3/GPR66 and FM-4/TGR-1. These receptors have been identified as neuromedin U (NMU) receptor type 1 and type 2, respectively. In this study, the physiological role of the novel peptide, NMS, on feeding regulation was investigated. Intracerebroventricular (icv) injection of NMS decreased 12-h food intake during the dark period in rats. This anorexigenic effect was more potent and persistent than that observed with the same dose of NMU. Neuropeptide Y, ghrelin, and agouti-related protein-induced food intake was counteracted by coadministration of NMS. Icv administration of NMS increased proopiomelanocortin mRNA expression in the arcuate nucleus (Arc) and CRH mRNA in the paraventricular nucleus (PVN). Pretreatment with SHU9119 (antagonist for α-MSH) and α-helical corticotropin-releasing factor-(9–41) (antagonist for CRH) attenuated NMS-induced suppression of 24-h food intake. After icv injection of NMS, Fos-immunoreactive cells were detected in both the PVN and Arc. When neuronal multiple unit activity was recorded in the PVN before and after icv injection of NMS, a significant increase in firing rate was observed 5 min after administration, and this increase continued for 100 min. These results suggest that the novel peptide, NMS, may be a potent anorexigenic hormone in the hypothalamus, and that expression of proopiomelanocortin mRNA in the Arc and CRH mRNA in the PVN may be involved in NMS action on feeding.
Creation of Estrogen Resistance in Vivo by Transgenic Overexpression of the Heterogeneous Nuclear Ribonucleoprotein-Related Estrogen Response Element Binding Protein
Authors: Chen Hong , Stuart William , Hu Bing , Nguyen Lisa , Huang Ganghua , Clemens Thomas L. , Adams John S.
Published: June 2005

Estrogen unresponsiveness among primate species can result from overexpression of a heterogeneous nuclear ribonucleoprotein (hnRNP) that competes with estrogen receptor (ER) for binding to the estrogen-response element (ERE). This hnRNP has been coined the “ERE-binding protein” (ERE-BP). The ERE-BP is a member of the hnRNP C-like subfamily of hnRNPs, traditionally considered to be single-strand RNA binding proteins designed for the stabilization and handling of pre-mRNA. To verify in vivo the dominant-negative actions of the ERE-BP to inhibit ER-ERE-directed transactivation and to avoid the potential for lethality from global overexpression of an hnRNP, we generated transgenic mice that overexpressed ERE-BP in breast tissue under the control of a whey acidic protein gene promoter. Graded overexpression of ERE-BP in transgenic mice was established. Founders were viable and fertile. Female transgenics in all lines gave birth to pups, but their ability to nurse was dependent on the level of ERE-BP expression in breast; high-ERE-BP expressors were unable to lactate. A gradient of impaired breast pheno(histo)type, from near normal to failed ductal development and lactational capacity, correlated with the relative level of transgene expression. ERE-BP, expressed either endogenously as a transgene or after transfection, colocalized with ERα in the nucleus of target cells. This work confirms that tissue-targeted overexpression of the ERE-BP can effectively block estrogen-ERα-ERE-directed action in vivo.
Topical Thyroid Hormone Accelerates Wound Healing in Mice
Authors: Safer Joshua D. , Crawford Tara M. , Holick Michael F.
Published: June 2005

Although the physiologic role of thyroid hormone in skin is not well understood, mounting evidence suggests that T3 plays an important role in epidermal proliferation. The goal of this project was to evaluate whether the topical application of supraphysiologic doses of T3 could accelerate wound healing. We evaluated mice treated with topical T3vs. the same mice receiving vehicle alone (Novasome A). Ten-millimeter diameter (79 mm2) dorsal skin wounds were established in all animals, and wounds were remeasured 4 d after injury. All animals were evaluated twice: once with the T3 treatment and once with the vehicle alone. Daily topical application of 150 ng T3 resulted in 58% greater wound closure relative to wounds on the same animals receiving vehicle alone (P < 0.001). Furthermore, we determined that wound healing-associated keratin 6 protein expression in hair follicle keratinocytes increased in a dose-dependent manner in vivo during topical T3 treatment. The data support our previous hypothesis that T3 is necessary for optimal wound healing. Now, we further suggest that topical thyroid hormone may be an inexpensive agent to hasten healing of certain wounds.
Adiponectin Gene Is Expressed in Multiple Tissues in the Chicken: Food Deprivation Influences Adiponectin Messenger Ribonucleic Acid Expression
Authors: Maddineni Sreenivasa , Metzger Shana , Ocón Olga , Hendricks Gilbert , Ramachandran Ramesh
Published: June 2005

Adiponectin is a cytokine hormone originally found to be secreted exclusively by white adipose tissue. However, recent evidences suggest that adiponectin is also produced in brown adipose tissue and skeletal muscle. The present study investigated the expression of adiponectin mRNA in various tissues in the chicken. We also studied the effect of food deprivation on adiponectin gene expression in adipose tissue, liver, anterior pituitary gland, and diencephalon in the chicken. The open reading frame of chicken adiponectin cDNA consists of 735 nucleotides that were 65–68% homologous to various mammalian adiponectin cDNAs. The deduced amino acid sequence of chicken adiponectin contains 22 glycine-X-Y repeats (in which X and Y represent any amino acid) at the N-terminal end as found in the mammalian adiponectin. By RT-PCR and Northern analysis, we detected chicken adiponectin mRNA transcript in adipose tissue, liver, anterior pituitary gland, diencephalon, skeletal muscle, liver, kidney, ovary, and spleen but not in blood. Adiponectin mRNA expression in various tissues was quantitated using real-time quantitative PCR and found to be the highest in adipose tissue, followed by liver, anterior pituitary, diencephalon, kidney, and skeletal muscle. We also found that adiponectin mRNA quantity was significantly decreased after a 48-h food deprivation in adipose tissue, liver, and anterior pituitary gland but not in diencephalon. Our results provide novel evidence that, unlike mammals, adiponectin gene is expressed in several tissues in the chicken and that its expression is influenced by food deprivation.
Fetal Programming: Excess Prenatal Testosterone Reduces Postnatal Luteinizing Hormone, But Not Follicle-Stimulating Hormone Responsiveness, to Estradiol Negative Feedback in the Female
Authors: Sarma Hirendra N. , Manikkam Mohan , Herkimer Carol , Dell’Orco James , Welch Kathleen B. , Foster Douglas L. , Padmanabhan Vasantha
Published: June 2005

Exposure of female sheep fetuses to excess testosterone (T) during early to midgestation produces postnatal hypergonadotropism manifest as a selective increase in LH. This hypergonadotropism may result from reduced sensitivity to estradiol (E2) negative feedback and/or increased pituitary sensitivity to GnRH. We tested the hypothesis that excess T before birth reduces responsiveness of LH and FSH to E2 negative feedback after birth. Pregnant ewes were treated with T propionate (100 mg/kg in cotton seed oil) or vehicle twice weekly from d 30–90 gestation. Responsiveness to E2 negative feedback was assessed at 12 and 24 wk of age in the ovary-intact female offspring. Our experimental strategy was first to arrest follicular growth and reduce endogenous E2 by administering the GnRH antagonist (GnRH-A), Nal-Glu (50 μg/kg sc every 12 h for 72 h), and then provide a fixed amount of exogenous E2 via an implant. Blood samples were obtained every 20 min at 12 wk and every 10 min at 24 wk before treatment, during and after GnRH-A treatment both before and after E2 implant. GnRH-A ablated LH pulsatility, reduced FSH by approximately 25%, and E2 production diminished to near detection limit of assay at both ages in both groups. Prenatal T treatment produced a precocious and selective reduction in responsiveness of LH but not FSH to E2 negative feedback, which was manifest mainly at the level of LH/GnRH pulse frequency. Collectively, these findings support the hypothesis that prenatal exposure to excess T decreases postnatal responsiveness to E2 inhibitory feedback of LH/GnRH secretion to contribute to the development of hypergonadotropism.
Tetrahydrogestrinone Is an Androgenic Steroid that Stimulates Androgen Receptor-Mediated, Myogenic Differentiation in C3H10T1/2 Multipotent Mesenchymal Cells and Promotes Muscle Accretion in Orchidectomized Male Rats
Authors: Jasuja R. , Catlin D. H. , Miller A. , Chang Y.-C. , Herbst K. L. , Starcevic B. , Artaza J. N. , Singh R. , Datta G. , Sarkissian A. , Chandsawangbhuwana C. , Baker M. , Bhasin S.
Published: June 2005

The discovery of tetrahydrogestrinone (THG) abuse by several elite athletes led the U.S. Congress to declare it a controlled substance, although conclusive evidence of its anabolic/androgenic activity is lacking. We determined whether THG affects myogenic differentiation and androgen receptor (AR)-mediated signaling, whether it binds to AR, and whether it has androgenic and anabolic effects in vivo. Accordingly, we measured the dissociation constant for THG with a fluorescence anisotropy assay using recombinant AR-ligand binding domain. The AR nuclear translocation and myogenic activity of androstenedione were evaluated in mesenchymal, multipotent C3H10T1/2 cells. We performed molecular modeling of the THG:AR interaction. The androgenic/anabolic activity was evaluated in orchidectomized rats. THG bound to AR with an affinity similar to that of dihydrotestosterone. In multipotent C3H10T1/2 cells, THG upregulated AR expression, induced AR nuclear translocation, dose dependently increased the area of myosin heavy chain type II-positive myotubes, and up-regulated myogenic determination and myosin heavy chain type II protein expression. The interaction between AR and the A ring of THG was similar to that between AR and the A ring of dihydrotestosterone, but the C17 and C18 substituents in THG had a unique stabilizing interaction with AR. THG administration prevented the castration-induced atrophy of levator ani, prostate gland, and seminal vesicles and loss of fat-free mass in orchidectomized rats. We conclude that THG is an anabolic steroid that binds to AR, activates AR-mediated signaling, promotes myogenesis in mesenchymal multipotent cells, and has anabolic and androgenic activity in vivo. This mechanism-based approach should be useful for rapid screening of anabolic/androgenic agents.
Activation of Caspase 8 in the Pituitaries of Streptozotocin-Induced Diabetic Rats: Implication in Increased Apoptosis of Lactotrophs
Authors: Arroba Ana I. , Frago Laura M. , Argente Jesús , Chowen Julie A.
Published: June 2005

Lactotroph cell death is increased in streptozotocin-induced diabetic rats. To determine the mechanism involved, cell death proteins were accessed in pituitaries of diabetic (streptozotocin at 65 mg/kg, 2 months evolution) and control male rats by Western blot analysis and double immunohistochemistry. The intact and cleaved forms of caspase 9 were increased in diabetic rat pituitaries compared with controls. Although the proforms of caspases 3, 6, and 7 were increased in diabetic rat pituitaries, their activated forms were either unchanged or decreased. Activation of these effector caspases may be blocked by the increased expression of X-chromosome-linked inhibitor of apoptosis protein (XIAP) in diabetic rat pituitaries. However, in diabetic rats, XIAP expression in lactotrophs was decreased, suggesting that this cell type is not protected. Caspase 8, p53, and nuclear factor κB were more highly activated in diabetic rat pituitaries, with caspase 8 colocalization in lactotrophs being increased. These results suggest that, in the pituitaries of diabetic rats, the cascades of normal cell turnover are partially inhibited, possibly via XIAP, and this may be cell specific. Furthermore, activation of the extrinsic cell-death pathway, including activation of caspase 8, may underlie the diabetes-associated increase in lactotroph death.
Binding of Estrogen Receptor β to Estrogen Response Element in Situ Is Independent of Estradiol and Impaired by Its Amino Terminus
Authors: Huang Jing , Li Xiaodong , Maguire Casey A. , Hilf Russell , Bambara Robert A. , Muyan Mesut
Published: June 2005

The functions of 17β-estradiol (E2) are mediated by estrogen receptor (ER) α and β. ERs display similar DNA- and ligand-binding properties in vitro. However, ERβ shows lower transcriptional activity than ERα from the estrogen response element (ERE)-dependent signaling. We predicted that distinct amino termini contribute to differences in transcription efficacies of ERs by affecting in situ ER-ERE interactions. We used chromatin immunoprecipitation and a novel in situ ERE competition assay, which is based on the ability of ER to compete for ERE binding with a designer activator that constitutively induces transcription from an ERE-driven reporter construct. Interference of activator-mediated transcription by unliganded or liganded ERs was taken as an indication of ER-ERE interaction. Results revealed that ERs interacted with ERE similarly in the absence of E2. However, E2 enhanced the ERE binding of ERα but not that of ERβ. The removal of the amino terminus increased the ERβ-ERE interaction independent of E2. The ERβ amino terminus also prevented E2-mediated enhancement of the chimeric ERα-ERE interaction. Thus, the amino terminus of ERβ impairs the binding of ERβ to ERE. The abrogation of ligand-dependent activation function 2 of the amino-terminally truncated ERβ resulted in the manifestation of E2 effect on ERβ-ERE interaction. This implies that E2-mediated enhancement of ERβ-ERE interaction is masked by the activation function 2, whereas the intact amino terminus is a dominant region that decreases the binding of ERβ to ERE. Thus, ERβ-ERE interaction is independent of E2 and is impaired by its amino terminus. These findings provide an additional explanation for differences between ERα and ERβ functions that could differentially affect the physiology and pathophysiology of E2 signaling.
Molecular Analysis of a Congenital Iodide Transport Defect: G543E Impairs Maturation and Trafficking of the Na+/I− Symporter
Authors: De la Vieja Antonio , Ginter Christopher S. , Carrasco Nancy
Published: June 2005

The Na+/I− symporter (NIS) is a key membrane glycoprotein that mediates active I− transport in the thyroid and other tissues. Upon isolation of the cDNA encoding NIS, 10 NIS mutations that cause congenital iodide transport defect have been identified. Three of these mutations (T354P, G395R, and Q267E) have been thoroughly characterized at the molecular level. All three NIS mutant proteins are correctly targeted to the plasma membrane; however, whereas Q267E displays minimal activity, T354P and G395R are inactive. Here, we show that in contrast to these mutants, G543E NIS matures only partially and is retained intracellularly; thus, it is not targeted properly to the cell surface, apparently because of faulty folding. These findings indicate that the G543 residue plays significant roles in NIS maturation and trafficking. Remarkably, NIS activity was rescued by small neutral amino acid substitutions (volume < 129 Å3) at this position, suggesting that G543 is in a tightly packed region of NIS.
Depletion of Bmp2, Bmp4, Bmp7 and Spemann organizer signals induces massive brain formation inXenopusembryos
Authors: Reversade Bruno , Kuroda Hiroki , Lee Hojoon , Mays Ashley , De Robertis Edward M.
Published: June 2005

To address the patterning function of the Bmp2, Bmp4 and Bmp7 growth factors, we designed antisense morpholino oligomers (MO) that block their activity in Xenopus laevis. Bmp4 knockdown was sufficient to rescue the ventralizing effects caused by loss of Chordin activity. Double Bmp4 and Bmp7 knockdown inhibited tail development. Triple Bmp2/Bmp4/Bmp7 depletion further compromised trunk development but did not eliminate dorsoventral patterning. Unexpectedly, we found that blocking Spemann organizer formation by UV treatment or β-Catenin depletion caused BMP inhibition to have much more potent effects, abolishing all ventral development and resulting in embryos having radial central nervous system (CNS) structures. Surprisingly,dorsal signaling molecules such as Chordin, Noggin, Xnr6 and Cerberus were not re-expressed in these embryos. We conclude that BMP inhibition is sufficient for neural induction in vivo, and that in the absence of ventral BMPs, Spemann organizer signals are not required for brain formation.
Matrix metalloproteinases are required for retinal ganglion cell axon guidance at select decision points
Authors: Hehr Carrie L. , Hocking Jennifer C. , McFarlane Sarah
Published: June 2005

Axons receive guidance information from extrinsic cues in their environment in order to reach their targets. In the frog Xenopus laevis, retinal ganglion cell (RGC) axons make three key guidance decisions en route through the brain. First, they cross to the contralateral side of the brain at the optic chiasm. Second, they turn caudally in the mid-diencephalon. Finally,they must recognize the optic tectum as their target. The matrix metalloproteinase (MMP) and a disintegrin and metalloproteinase (ADAM)families are zinc (Zn)-dependent proteolytic enzymes. The latter functions in axon guidance, but a similar role has not yet been identified for the MMP family. Our previous work implicated metalloproteinases in the guidance decisions made by Xenopus RGC axons. To test specifically the importance of MMPs, we used two different in vivo exposed brain preparations in which RGC axons were exposed to an MMP-specific pharmacological inhibitor(SB-3CT), either as they reached the optic chiasm or as they extended through the diencephalon en route to the optic tectum. Interestingly, SB-3CT affected only two of the guidance decisions, with misrouting defects at the optic chiasm and tectum. Only at higher concentrations was RGC axon extension also impaired. These data implicate MMPs in the guidance of vertebrate axons, and suggest that different metalloproteinases function to regulate axon behaviour at distinct choice points: an MMP is important in guidance at the optic chiasm and the target, while either a different MMP or an ADAM is required for axons to make the turn in the mid-diencephalon.
Abnormalities in cartilage and bone development in the Apert syndrome FGFR2+/S252W mouse
Authors: Wang Yingli , Xiao Ran , Yang Fan , Karim Baktiar O. , Iacovelli Anthony J. , Cai Juanliang , Lerner Charles P. , Richtsmeier Joan T. , Leszl Jen M. , Hill Cheryl A. , Yu Kai , Ornitz David M. , Elisseeff Jennifer , Huso David L. , Jabs Ethylin Wang
Published: June 2005

Apert syndrome is an autosomal dominant disorder characterized by malformations of the skull, limbs and viscera. Two-thirds of affected individuals have a S252W mutation in fibroblast growth factor receptor 2(FGFR2). To study the pathogenesis of this condition, we generated a knock-in mouse model with this mutation. The Fgfr2+/S252W mutant mice have abnormalities of the skeleton, as well as of other organs including the brain, thymus, lungs, heart and intestines. In the mutant neurocranium, we found a midline sutural defect and craniosynostosis with abnormal osteoblastic proliferation and differentiation. We noted ectopic cartilage at the midline sagittal suture, and cartilage abnormalities in the basicranium, nasal turbinates and trachea. In addition, from the mutant long bones, in vitro cell cultures grown in osteogenic medium revealed chondrocytes, which were absent in the controls. Our results suggest that altered cartilage and bone development play a significant role in the pathogenesis of the Apert syndrome phenotype.
Direct and indirect roles of CNS dorsal midline cells in choroid plexus epithelia formation
Authors: Currle D. Spencer , Cheng Xun , Hsu Ching-mei , Monuki Edwin S.
Published: June 2005

Choroid plexus (CP) produces the cerebrospinal fluid (CSF) of the central nervous system (CNS), but little is known about the mechanisms underlying development of this important tissue. CP forms in the hindbrain (4th ventricle), diencephalon (3rd ventricle) and dorsomedial telencephalon bilaterally (lateral ventricles). All of these sites lie at or near the embryonic dorsal midline (DM), which acts as a CNS patterning center. We therefore examined DM-CP relationships using normal and Gdf7 (Bmp12)transgenic embryos to fate map or ablate DM cells. These studies revealed a Gdf7 fate map that includes most CP epithelial (CPe) cells of the hindbrain and diencephalon. In the telencephalon, Gdf7 cell lineages were found in the small anterior domain of telencephalic CPe (tCPe), but its large posterior domain was devoid of these lineages. Anterior and posterior tCPe domains,which arise within a contiguous field separate from diencephalic CPe, also exhibited different patterns of apoptosis. Despite lacking Gdf7 cell lineages,the posterior tCPe domain failed to form after ablating Gdf7-expressing DM cells at neural tube stages. The tCPe loss was associated with abrogation of high-level bone morphogenetic protein (Bmp) signaling, which is known to be required for tCPe induction. Taken together, these studies demonstrate intimate DM-CPe relationships throughout the CNS and highlight two distinct tCPe domains, including a posterior domain whose genesis depends on DM cells in a non-cell-autonomous fashion.
C. elegans sperm bud vesicles to deliver a meiotic maturation signal to distant oocytes
Authors: Kosinski Mary , McDonald Kent , Schwartz Joel , Yamamoto Ikuko , Greenstein David
Published: June 2005

The major sperm protein (MSP) is the central cytoskeletal element required for actin-independent motility of nematode spermatozoa. MSP has a dual role in Caenorhabditis elegans reproduction, functioning as a hormone for both oocyte meiotic maturation and ovarian muscle contraction. The identification of the signaling function of MSP raised the question, how do spermatozoa, which are devoid of ribosomes, ER and Golgi, release a cytoplasmic protein lacking a signal sequence? Here, we provide evidence that MSP export occurs by the budding of novel vesicles that have both inner and outer membranes with MSP sandwiched in between. MSP vesicles are apparently labile structures that generate long-range MSP gradients for signaling at the oocyte cell surface. Both spermatozoa and non-motile spermatids bud MSP vesicles, but their stability and signaling properties differ. Budding protrusions from the cell body contain MSP, but not the MSD proteins, which counteract MSP filament assembly. We propose that MSP generates the protrusive force for its own vesicular export.
Lateral inhibition in proneural clusters: cis-regulatory logic and default repression by Suppressor of Hairless
Authors: Castro Brian , Barolo Scott , Bailey Adina M. , Posakony James W.
Published: June 2005

Lateral inhibition, wherein a single cell signals to its neighbors to prevent them from adopting its own fate, is the best-known setting for cell-cell communication via the Notch (N) pathway. During peripheral neurogenesis in Drosophila, sensory organ precursor (SOP) cells arise within proneural clusters (PNCs), small groups of cells endowed with SOP fate potential by their expression of proneural transcriptional activators. SOPs use N signaling to activate in neighboring PNC cells the expression of multiple genes that inhibit the SOP fate. These genes respond transcriptionally to direct regulation by both the proneural proteins and the N pathway transcription factor Suppressor of Hairless [Su(H)], and their activation is generally highly asymmetric; i.e. only in the inhibited(non-SOP) cells of the PNC, and not in SOPs. We show that the substantially higher proneural protein levels in the SOP put this cell at risk of inappropriately activating the SOP-inhibitory genes, even without input from N-activated Su(H). We demonstrate that this is prevented by direct `default'repression of these genes by Su(H), acting through the same binding sites it uses for activation in non-SOPs. We show that de-repression of even a single N pathway target gene in the SOP can extinguish the SOP cell fate. Finally, we define crucial roles for the adaptor protein Hairless and the co-repressors Groucho and CtBP in conferring repressive activity on Su(H) in the SOP. Our work elucidates the regulatory logic by which N signaling and the proneural proteins cooperate to create the neural precursor/epidermal cell fate distinction during lateral inhibition.
Comprehensive Antibody Epitope Mapping of the Nucleocapsid Protein of Severe Acute Respiratory Syndrome (SARS) Coronavirus: Insight into the Humoral Immunity of SARS
Authors: Liang Yunfei , Wan Ying , Qiu Li-wen , Zhou Jingran , Ni Bing , Guo Bo , Zou Qiang , Zou Liyun , Zhou Wei , Jia Zhengcai , Che Xiao-yan , Wu Yuzhang
Published: June 2005

Background: The epidemic outbreak of severe acute respiratory syndrome (SARS) posed a worldwide threat to public health and economic stability. Although the pandemic has been contained, concerns over its recurrence remain. It is essential to identify specific diagnostic agents and antiviral vaccine candidates to fight this highly contagious disease.

Methods: We generated 14 monoclonal antibodies (mAbs) specific to the SARS coronavirus (SARS-CoV) nucleocapsid (N) protein and used these to thoroughly map the N protein antigenic determinants. We identified the immunodominant antigenic sites responsible for the antibodies in sera from SARS patients and antisera from small animals and differentiated the linear from the conformational antibody-combining sites comprising the natural epitopes by use of yeast surface display.

Results: We identified 5 conformational and 3 linear epitopes within the entire N protein; 3 conformational and 3 linear epitopes were immunodominant. The antibody responses to the N protein fragments in mammalian sera revealed that 3 regions of the N protein are strong antigenic domains. We expanded the specificity of the N protein epitope and identified 4 novel conformational epitopes (amino acids 1–69, 68–213, 212–341, and 337–422).

Conclusion: The antigenic structures identified for the SARS-CoV N protein, the epitope-specific mAbs, and the serum antibody profile in SARS patients have potential use in the clinical diagnosis and understanding of the protective immunity to SARS-CoV.
Genetic Interaction of Lobe With Its Modifiers in Dorsoventral Patterning and Growth of the Drosophila Eye
Authors: Singh Amit , Chan Jeeder , Chern Joshua J , Choi Kwang-Wook
Published: June 2005

Dorsoventral (DV) patterning is essential for growth of the Drosophila eye. Recent studies suggest that ventral is the default state of the early eye, which depends on Lobe (L) function, and that the dorsal fate is established later by the expression of the dorsal selector gene pannier (pnr). However, the mechanisms of regulatory interactions between L and dorsal genes are not well understood. For studying the mechanisms of DV patterning in the early eye disc, we performed a dominant modifier screen to identify additional genes that interact with L. The criterion of the dominant interaction was either enhancement or suppression of the L ventral eye loss phenotype. We identified 48 modifiers that correspond to 16 genes, which include fringe (fng), a gene involved in ventral eye patterning, and members of both Hedgehog (Hh) and Decapentaplegic (Dpp) signaling pathways, which promote L function in the ventral eye. Interestingly, 29% of the modifiers (6 enhancers and 9 suppressors) identified either are known to interact genetically with pnr or are members of the Wingless (Wg) pathway, which acts downstream from pnr. The detailed analysis of genetic interactions revealed that pnr and L mutually antagonize each other during second instar of larval development to restrict their functional domains in the eye. This time window coincides with the emergence of pnr expression in the eye. Our results suggest that L function is regulated by multiple signaling pathways and that the mutual antagonism between L and dorsal genes is crucial for balanced eye growth.
Maximum Sustainable Yield and Bycatch Minimization “to the Extent Practicable”
Authors: Powers Joseph E.
Published: June 2005

Two goals of marine fisheries management in the USA are (1) to achieve maximum sustainable yield (MSY) and (2) to minimize bycatch “to the extent practicable.” However, the determination of MSY is contingent on the selectivity of the various fisheries involved and the mix of these fisheries that managers desire. I compare several methods of computing MSY and associated parameters that involve alternative assumptions about the balance between target and bycatch fisheries. These methods were evaluated using a deterministic population simulation model. Additionally, biological risk was evaluated by computing relative spawning levels in the presence and absence of bycatch. While the choice of the method will largely be driven by socioeconomic factors, some implications for management are discussed. Before analysts can calculate MSY and associated parameters, managers must determine their desired mix of fishing and the definition of “to the extent practicable.”
Seasonal Movement Patterns of Stream‐Dwelling Rainbow Trout in North‐Central British Columbia, Canada
Authors: Mellina Eric , Hinch Scott G. , MacKenzie Kirsten D. , Pearson Greg
Published: June 2005

Movement forms an important part of salmonid life histories, and although previous studies have largely concluded that the majority of stream‐dwelling salmonids are sedentary, the paradigm of restricted movement has been questioned by recent findings. We conducted a 3‐year study to examine the seasonal movement patterns of rainbow trout Oncorhynchus mykiss in three small, lake‐headed streams situated in north‐central British Columbia and to determine whether movement was related to environmental conditions. Two of the three streams were subjected to streamside clear‐cut logging during the second year. The trout in our study streams generally remained sedentary during the summer, autumn, and winter seasons for a period of approximately 1–2 years before undertaking long‐range (>372–607‐m) movements during springtime. These springtime long‐range movements were most closely linked to stream discharge, as they generally ceased with the onset of summer low flows (<10–20 L/s), but they did not resume in the autumn despite increasing flows. Links between movement patterns and stream temperature were less clear, as long‐range movements occurred over a wide range (0–30°C) of temperatures. The predominant direction of long‐range movements was lakeward. All three streams supported relatively large populations of resident trout during the summer and autumn months; densities of 0.4–1.0 trout/m2 were primarily associated with age‐0 to age‐2 fish. Our data provide insights into how the movement patterns and life history strategies of stream‐dwelling rainbow trout are intertwined, as well as how the timing of sampling efforts may be an important factor when assessing whether stream‐dwelling fish are sedentary or mobile.
Ecological Consequences of Swim Bladder Noninflation for Larval Yellow Perch
Authors: Czesny Sergiusz J. , Graeb Brian D. S. , Dettmers John M.
Published: June 2005

Swim bladder inflation is a fundamental developmental step during the larval stage of many fishes. Although the physiological mechanisms of swim bladder inflation are well documented, the ecological costs of noninflation are poorly understood. If high proportions of newly hatched fish larvae fail to inflate their swim bladders and swim bladder noninflation negatively affects individual survival probability, the population‐level effects could be dramatic. To determine whether fish larvae without inflated swim bladders perform differently than their conspecifics with inflated swim bladders, we compared growth rate, feeding selectivity and efficiency, susceptibility to predation, oxygen consumption, and starvation mortality of two size‐classes of larval yellow perch Perca flavescens with and without inflated swim bladders in a series of experiments. In the laboratory, growth rates of yellow perch with uninflated swim bladders were less than those for fish with inflated swim bladders, and fish with inflated swim bladders fed more efficiently than those with uninflated swim bladders. In addition, predation risk, metabolic demands, and vulnerability to starvation mortality were higher in fish lacking an inflated swim bladder than in fish with an inflated swim bladder. In the field, individuals with uninflated swim bladders were smaller than their conspecifics with inflated swim bladders. The relative occurrence of yellow perch larvae without inflated swim bladders declined as the sampling season progressed until only fish with inflated swim bladders were collected. Our results demonstrate that a larval yellow perch's failure to inflate its swim bladder results in a higher probability of dying. Thus, on the population scale, the factors affecting swim bladder inflation among larval fishes may have a profound effect on recruitment dynamics.
Influences of Spawning Habitat Characteristics and Interstitial Predators on Lake Trout Egg Deposition and Mortality
Authors: Claramunt Randall M. , Jonas Jory L. , Fitzsimons John D. , Marsden J. Ellen
Published: June 2005

To understand the factors affecting natural recruitment of lake trout Salvelinus namaycush, we evaluated natural egg deposition, the rate of egg loss of seeded eggs, and the relationship of interstitial predators to egg mortality at a protected nearshore lake trout spawning area in Lake Michigan. Egg mortality and predator densities were evaluated with collection bags that were buried above the drop‐off on spawning substrate at 1‐, 3‐, and 9‐m depths. Habitat selection by spawning lake trout was probably related to the coverage by periphyton and zebra mussels Dreissena polymorpha given that abiotic characteristics of the spawning habitat such as slope (55– 65°), interstitial depth (30–50 cm), and substrate type did not differ across depths. The results of seeding eggs during spawning and recovering them throughout the incubation period (2–177 d) indicated that egg mortality was extremely high early in the spawning period: Over 40% of seeded eggs were lost by 2 d and over 80% of the eggs were lost after only 2 weeks. The rate of egg loss declined significantly after the spawning period, possibly as a result of declining water temperature, which caused reduced predator activity, and ice cover, which reduced the impact of physical disturbance. The greatest proportions of seeded eggs were recovered at the shallowest depths (12.5 ± 1.2% [mean ± SE] at 1 m and 9.0 ± 1.5% at 3 m), where predator densities averaged 11.4 ± 1.8/m2; a significantly smaller proportion was recovered at 9 m (3.9 ± 1.2), where predator densities were highest (22.3 ± 2.0/m2). Because lake trout preferred the shallowest depth for spawning and predation was lowest at this depth, we conclude that this strategy improved the probability of egg survival.
Catch Rates Relative to Angler Party Size with Implications for Monitoring Angler Success
Authors: Miranda L. E.
Published: June 2005

Angler catch rates often are used to monitor angler success, assess the need for additional management actions, and evaluate the effectiveness of management practices. Potential linkages between catch rate and angler party size were examined to assess how party size might affect the use of catch rate as an index of angler success in recreational fisheries. Data representing 22,355 completed interviews conducted at access points in lakes and reservoirs throughout Mississippi during 1987–2003 were analyzed. Total party catch was not proportional to total party effort; thus, catch rate decreased as party size increased. Depending on the taxa targeted, the average catch rate per angler decreased 40–50% between parties of one and parties of two, although subsequent decreases were less substantial. Because party size accounted for a considerable portion of the variability in catch rate over time and space, failure to remove this variability weakens the manager's ability to detect differences or changes in catch rates. Therefore, the use of catch rates to monitor fisheries may be inappropriate unless party size is taken into account. Party size may influence the angler's ability to catch fish through a variety of processes, including partitioning a limited number of catchable fish among members of a party and party composition. When catch rates are used to estimate total catch rather than to index angler success, party size is not a concern.
Influence of Juvenile Size on the Age at Maturity of Individually Marked Wild Chinook Salmon
Authors: Scheuerell Mark D.
Published: June 2005

The age at maturity for an organism represents a trade‐off between survival and reproductive fitness and is controlled by both genetic factors and environmental conditions. In the case of Pacific salmon Oncorhynchus spp., most of our understanding of the importance of various drivers in determining age at maturity has relied on information from cohort analyses using average size and age conditions or from hatchery fish that might not reflect observed patterns in wild fish. I used 14 years of adult return data from individually passive integrated transponder (PIT)–tagged wild Chinook salmon O. tshawytscha from the Snake River to examine the influence of juvenile size on subsequent age at maturity. I also included information on the natal watershed as a surrogate for genetic influence. I found a significant, positive relationship between juvenile length and the proportion of adult salmon returning at age 4 versus age 5, but the effect of juvenile length varied among the three watersheds. This suggests that local environmental conditions supporting juvenile growth largely control the ultimate age composition for a given brood of this stock of salmon but that genetic differences also exist.
Responses by Pacific Halibut to Air Exposure: Lack of Correspondence among Plasma Constituents and Mortality
Authors: Davis M. W. , Schreck C. B.
Published: June 2005

Age‐1 and age‐2 Pacific halibut Hippoglossus stenolepis were exposed to a range of times in air (0–60 min) and air temperatures (10°C or 16°C) that simulated conditions on deck after capture to test for correspondence among responses in plasma constituents and mortality. Pacific halibut mortality generally did not correspond with cortisol, glucose, sodium, and potassium since the maximum observed plasma concentrations were reached after exposure to 30 min in air, while significant mortality occurred only after exposure to 40 min in air for age‐1 fish and 60 min in air for age‐2 fish. Predicting mortality in discarded Pacific halibut using these plasma constituents does not appear to be feasible. Lactate concentrations corresponded with mortality in age‐1 fish exposed to 16°C and may be useful predictors of discard mortality under a limited set of fishing conditions.
Incidence and Physiological Consequences of Decompression in Smallmouth Bass after Live‐Release Angling Tournaments
Authors: Morrissey Michael B. , Suski Cory D. , Esseltine Kevin R. , Tufts Bruce L.
Published: June 2005

Decompression can be an important problem for fish that are rapidly brought to the surface. The main objectives of this study were to (1) examine the incidence of external signs of decompression in smallmouth bass Micropterus dolomieu after live‐release angling tournaments on lakes with different depths, (2) determine the physiological changes in smallmouth bass that exhibit external decompression signs, and (3) identify the best methodological approaches for evaluating this type of disturbance. Our results indicate that decompression does not cause problems for smallmouth bass when tournaments are held on relatively shallow lakes. However, when tournament anglers have access to deep water (>5 m), significant numbers of smallmouth bass may exhibit decompression signs after these events. Decompression signs include swim bladder overinflation, increased plasma lactate, and increased activity of tissue enzymes in plasma. Tournament‐caught smallmouth bass exhibiting external signs of decompression also experience internal physiological changes, including significant elevations in the plasma levels of intracellular enzymes (lactate dehydrogenase [LDH]; enzyme number 1.1.1.27; creatine phosphokinase [CPK]; 2.7.3.2; and aspartate aminotransferase [AST]; 2.6.1.1), red blood cell lysis, and a larger anaerobic disturbance after the weigh‐in than observed in nondecompressed smallmouth bass. Additional laboratory experiments indicate that plasma AST activity may be the most useful indicator of the extent of tissue damage in decompressed smallmouth bass because it is highly correlated to plasma LDH and CPK levels but is not influenced by the blood sampling method.
Constrained closed‐loop control of depth of anaesthesia in the operating theatre during surgery
Authors: Mahfouf M.
Published: June 2005

The constrained version of generalized predictive control (GPC) which employs the quadratic programming (QP) approach is evaluated for on‐line administration of an anaesthetic drug in the operating theatre during surgery. In the first instance, a patient simulator was developed using a physiological model of the patient and the necessary control software was validated via a series of extensive simulation experiments. Such a validated system was then transferred into the operating theatre for a series of clinical evaluation trials. The clinical trials, which were performed with little involvement of the design engineer, led to a good regulation of unconsciousness using fixed‐parameters as well the adaptive version of the algorithm. Furthermore, the constrained algorithm displayed good robustness properties against disturbances such as high stimulus levels and allowed for safe and economically effective administration of the anaesthetic agent isoflurane. Copyright © 2005 John Wiley & Sons, Ltd.
Invasive neural prosthesis for neural signal detection and nerve stimulation
Authors: Gasson Mark , Hutt Benjamin , Goodhew Iain , Kyberd Peter , Warwick Kevin
Published: June 2005

This paper specifically examines the implantation of a microelectrode array into the median nerve of the left arm of a healthy male volunteer. The objective was to establish a bi‐directional link between the human nervous system and a computer, via a unique interface module. This is the first time that such a device has been used with a healthy human. The aim of the study was to assess the efficacy, compatibility, and long term operability of the neural implant in allowing the subject to perceive feedback stimulation and for neural activity to be detected and processed such that the subject could interact with remote technologies. A case study demonstrating real‐time control of an instrumented prosthetic hand by means of the bi‐directional link is given.

The implantation did not result in infection, and scanning electron microscope images of the implant post extraction have not indicated significant rejection of the implant by the body. No perceivable loss of hand sensation or motion control was experienced by the subject while the implant was in place, and further testing of the subject following the removal of the implant has not indicated any measurable long term defects. The implant was extracted after 96 days. Copyright © 2004 John Wiley & Sons, Ltd.
Neuro‐fuzzy uncertainty de‐coupling: a multiple‐model paradigm for fault detection and isolation
Authors: Uppal Faisel J. , Patton Ron J.
Published: June 2005

In this paper, a neuro‐fuzzy and de‐coupling fault diagnosis scheme (NFDFDS) is proposed for fault detection and isolation (FDI) of nonlinear dynamic systems. In this approach, powerful approximation and reasoning capabilities of neuro‐fuzzy models are combined with the de‐coupling capabilities of optimal observers to perform reliable fault detection and isolation. The neuro‐fuzzy model presented here is a special form of Takagi–Sugeno (TS) fuzzy model used to represent the system by a fuzzy fusion of local linear sub‐models. The necessary condition for the application of this FDI scheme is that this special form of the TS model can represent the nonlinear system, which is true for many practical systems. It is shown that if all the local models are stable and the corresponding local observers converge to the local models it can be expected that the global model is stable and the corresponding global observer will converge to the nonlinear input–output system. An application of FDI for an electro‐pneumatic valve actuator in a sugar factory is presented. Key issues of finding a suitable structure for detecting and isolatingninerealistic actuator faults are described. Copyright © 2004 John Wiley & Sons, Ltd.
Experimental studies of a new compact design four‐bed PSA equipment for producing oxygen
Authors: Zhou Li , Li Jie , Su Wei , Sun Yan , Zhou Yaping
Published: June 2005

A new compact design of pressure swing adsorption (PSA) equipment was presented. All columns of the PSA process reduced to disks that are stacked tightly together. The total size of the equipment was thus substantially reduced. The feasibility and the process performance of the new design were tested with a four‐bed process aiming to produce oxygen from air. The adsorbent used was zeolite molecular sieve ZMS‐5A. Although the process performance was limited by the relatively nonefficient adsorbent, the feasibility of the compact arrangement of disk columns was proven, and the advantages in the compensation of the thermal effect of adsorption and in the higher energy efficiency were also demonstrated. © 2005 American Institute of Chemical Engineers AIChE J, 2005
Temperature conversion (mesophilic to thermophilic) of municipal sludge digestion
Authors: de la Rubia M. A. , Romero L. I. , Sales D. , Perez M.
Published: June 2005

A protocol proposed is described here to characterize for the conversion from mesophilic to thermophilic conditions in a pilot‐scale anaerobic digester that operates with municipal mixed sludge. Furthermore, the performance of thermophilic operation relative to the previous mesophilic operating status was evaluated. The performance was evaluated in terms of a number of parameters that included organic removal rate (ORR) (kgVS/m3·d and kgCOD/m3·d), biogas and volumetric methane production rate (m3/m3·d), pH, total acidity (mg acetic acid/L) and acidity/alkalinity relationship. The digester was initially operated with an organic loading rate (OLR) of 1.26 kgVS/m3·d and a solids retention time (SRT) of 27 days under mesophilic conditions (35°C). The solids destruction efficiency was found to be 54.3%, while the volumetric biogas production in the digester reached 0.36 m3/m3·d. The strategy selected for the conversion from mesophilic to thermophilic digestion involved slowly increasing the temperature of the digester (0.38° C/d) until it reached 43°C. In this way, the temperature of the digester was raised from 43 to 45°C and then operated at a constant 45°C. The performance parameters at this temperature indicated that the digester was unstable. For this reason the OLR was decreased until feeding was suppressed. The reactor operated at 45°C for 32 days, and the temperature of the digester was then raised from 45 to 50°C (without feeding). The temperature was subsequently raised to 50 – 52°C with the system operating at variable SRT (65‐52 days), and finally, the temperature was increased at a rate of 0.13°C/d until it reached 55°C. At thermophilic conditions (55°C), the OLR studied was 1.48 kgVS/m3·d (SRT: 27 days), and under these conditions the solids destruction efficiency was 53.3% VS, and the biogas produced in the digester reached 0.32 m3/m3·d. © 2005 American Institute of Chemical Engineers AIChE J, 2005