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Selected AbstractsVitamin D Hormone Inhibits Osteoclastogenesis In Vivo by Decreasing the Pool of Osteoclast Precursors in Bone MarrowJOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2002Takeshi Shibata Abstract Previous observations that vitamin D hormone induces the expression of the receptor activator of nuclear factor ,B (NF-,B) ligand (RANKL), thereby stimulating osteoclastogenesis in vitro, led to the widespread belief that 1,,25-dihydroxyvitamin D3 [1,,25(OH)2D3] is a bone-resorbing hormone. Here, we show that alfacalcidol, a prodrug metabolized to 1,,25(OH)2D3, suppresses bone resorption at pharmacologic doses that maintain normocalcemia in an ovariectomized (OVX) mouse model of osteoporosis. Treatment of OVX mice with pharmacologic doses of alfacalcidol does not increase RANKL expression, whereas toxic doses that cause hypercalcemia markedly reduce the expression of RANKL. When bone marrow (BM) cells from OVX mice were cultured with sufficient amounts of macrophage colony-stimulating factor (M-CSF) and RANKL, osteoclastogenic activity was higher than in sham mice. Marrow cultures from alfacalcidol- or estrogen-treated OVX mice showed significantly less osteoclastogenic potential compared with those from vehicle-treated OVX mice, suggesting that the pool of osteoclast progenitors in the marrow of vitamin D-treated mice as well as estrogen-treated mice was decreased. Frequency analysis showed that the number of osteoclast progenitors in bone marrow was increased by OVX and decreased by in vivo treatment with alfacalcidol or estrogen. We conclude that the pharmacologic action of active vitamin D in vivo is to decrease the pool of osteoclast progenitors in BM, thereby inhibiting bone resorption. Because of its unusual activity of maintaining bone formation while suppressing bone resorption, in contrast to estrogens that depress both processes, vitamin D hormone and its bone-selective analogs may be useful for the management of osteoporosis. [source] AN ASSESSMENT OF VARIABILITY IN THEROPOD DINOSAUR REMAINS FROM THE BATHONIAN (MIDDLE JURASSIC) OF STONESFIELD AND NEW PARK QUARRY, UK AND TAXONOMIC IMPLICATIONS FOR MEGALOSAURUS BUCKLANDII AND ILIOSUCHUS INCOGNITUSPALAEONTOLOGY, Issue 4 2009ROGER B. J. BENSON Abstract:, The assemblage of large-bodied theropod remains from the Taynton Limestone Formation (middle Bathonian) of Stonesfield, Oxfordshire and the Chipping Norton Limestone Formation (lowest Bathonian) of New Park Quarry, Gloucestershire, UK is interpreted as monospecific. An assessment of morphological variation in theropod fossils from these localities reveals no taxonomically-significant variation among remains representing large-bodied individuals. Previous observations of anatomical variation among femora, ilia and scapulocoracoids are attributed to postmortem damage and deformation. Referral of all such material to the first named dinosaur taxon, Megalosaurus bucklandii Mantell, is therefore justified. ,Iliosuchus incognitus' lacks autapomorphies and is a nomen dubium. However, other remains of small-bodied theropods from Stonesfield indicate a minimum of two small-bodied taxa that are distinct from M. bucklandii. [source] Comparison of the antilipolytic effects of an A1 adenosine receptor partial agonist in normal and diabetic ratsDIABETES OBESITY & METABOLISM, Issue 2 2009A. K. Dhalla Introduction and Aims:, Elevated plasma free fatty acid (FFA) concentrations play a role in the pathogenesis of type 2 diabetes (2DM). Antilipolytic agents that reduce FFA concentrations may be potentially useful in the treatment of 2DM. Our previous observation that CVT-3619 lowered plasma FFA and triglyceride concentrations in rats and enhanced insulin sensitivity in rodents with dietary-induced forms of insulin resistance suggested that it might be of use in the treatment of patients with 2DM. The present study was undertaken to compare the antilipolytic effects of CVT-3619 in normal (Sprague Dawley, SD) and Zucker diabetic fatty (ZDF) rats. Results:, ZDF rats had significantly higher fat pad weight, glucose, insulin and FFA concentrations than those of SD rats. EC50 values for forskolin-stimulated FFA release from isolated adipocytes from SD and ZDF rats were 750 and 53 nM, respectively (p < 0.05). Maximal forskolin stimulation of FFA release was significantly (p < 0.01) less in ZDF rats (133 ± 60 ,M) compared with SD rats (332 ± 38 ,M). EC50 values for isoproterenol to increase lipolysis in adipocytes from SD and ZDF rats were 2 and 7 nM respectively. Maximal isoproterenol-stimulated lipolysis was significantly (p < 0.01) lower in adipocytes from ZDF rats (179 ± 23 ,M) compared with SD rats (343 ± 27 ,M). Insulin inhibited lipolysis in adipocytes from SD rats with an IC50 value of 30 pM, whereas adipocytes from ZDF rats were resistant to the antilipolytic actions of insulin. In contrast, IC50 values for CVT-3619 to inhibit the release of FFA from SD and ZDF adipocytes were essentially the same (63 and 123 nM respectively). CVT-3619 inhibited lipolysis more than insulin in both SD (86 vs. 46%, p < 0.001) and ZDF (80 vs. 13%, p < 0.001) adipocytes. In in vivo experiments, CVT-3619 (5 mg/kg, PO) lowered FFA to a similar extent in both groups. Plasma concentrations of CVT-3619 were not different in SD and ZDF rats. There was no significant difference in the messenger RNA expression of the A1 receptors relative to ,-actin expression in adipocytes from SD (0.98 ± 0.2) and ZDF rats (0.99 ± 0.3). Conclusion:, The antilipolytic effects of CVT-3619 appear to be independent of insulin resistance and animal model. [source] Detailed characterization of polydnavirus immunoevasive proteins in an endoparasitoid waspFEBS JOURNAL, Issue 10 2002Kohjiro Tanaka Polydnaviruses are a unique group of insect viruses in terms of their obligate and symbiotic associations with some parasitic wasps. The Cotesia kariyai polydnavirus (CkPDV) replicates only in ovarian calyx cells of C. kariyai female wasps and is injected into the wasp's host, the armyworm Pseudaletia separata, along with the eggs. A previous study indicated the possibility that one of the CkPDV surface proteins mediates immunoevasion by the wasp from the encapsulation reaction of the host insect's hemocytes. This protein was named immunoevasive protein (IEP). The present studies substantially confirmed the previous observation by showing that an anti-IEP IgG neutralizes immunoevasive activity on the wasp eggs. Further, we isolated the IEP homologue (IEP-2) cDNA and IEP (IEP-1) cDNA, sequenced them and found that both are cysteine-rich proteins, each containing epidermal growth factor (EGF)-like repeats. IEP genes were not found to reside in the CkPDV genome, but in the wasp chromosomal DNA. IEPs are synthesized in the female reproductive tract and their expression was detected from 4 days after pupation, 1 day later than expression of the virus capsid proteins. In situ hybridization and immunocytochemistry indicated that the lateral oviduct cells of the reproductive tracts produce IEP-1/IEP-2 mRNAs and secrete the proteins into the oviduct. These data suggest that the expression pattern and localization of IEPs are different from other components of CkPDV virions. [source] A female Lucifer Hummingbird (Calothorax lucifer) with iridescent chin feathersJOURNAL OF FIELD ORNITHOLOGY, Issue 1 2006Raúl Ortiz-Pulido ABSTRACT We report an observation of a female Lucifer Hummingbird (Calothorax lucifer) with iridescent feathers on the chin, resembling the plumage of the juvenile male. The female and nest were found in a xeric shrubland in Barranca de Metztitlán Biosphere Reserve, Hidalgo State, Mexico. This is the first definitive report of a breeding female with such plumage, supporting a previous observation in which sex was not confirmed by behavior. Although this condition appears be rare in female Lucifer Hummingbirds, females in other species of hummingbirds exhibit much variation in the amount of iridescent plumage on the chin and in some, such as Costa's Hummingbirds (Calypte costae), females commonly exhibit colored feathers on the chin. SINOPSIS Reportamos una observacion de una hembra de colibrí Lucifer (Calothorax lucifer) con plumas iridiscentes en el babero, parecidas al plumaje de un macho juvenil. La hembra, la cual estaba incubando, fue encontrada en un área arbustiva xerofítica en la Reserva Biosférica Barranca de Metztitlan, en Hidalgo, México. Este es el primer informe definitivo de una hembra reproductora con este tipo de plumaje, en apoyo a una observación previa en donde el sexo no fue confirmado. Esta condición parece ser rara en estas aves en contraste con otras especies de zumbadores como Calypte costae, pero común en otras especies dimórficas de México y de los Estados Unidos. [source] Glucose-dependent insulinotropic polypeptide (GIP) and its receptor (GIPR): Cellular localization, lesion-affected expression, and impaired regenerative axonal growthJOURNAL OF NEUROSCIENCE RESEARCH, Issue 8 2009Bettina A. Buhren Abstract Glucose-dependent insulinotropic polypeptide (GIP) was initially described to be rapidly regulated by endocrine cells in response to nutrient ingestion, with stimulatory effects on insulin synthesis and release. Previously, we demonstrated a significant up-regulation of GIP mRNA in the rat subiculum after fornix injury. To gain more insight into the lesion-induced expression of GIP and its receptor (GIPR), expression profiles of the mRNAs were studied after rat sciatic nerve crush injury in 1) affected lumbar dorsal root ganglia (DRG), 2) spinal cord segments, and 3) proximal and distal nerve fragments by means of quantitative RT-PCR. Our results clearly identified lesion-induced as well as tissue type-specific mRNA regulation of GIP and its receptor. Furthermore, comprehensive immunohistochemical stainings not only confirmed and exceeded the previous observation of neuronal GIP expression but also revealed corresponding GIPR expression, implying putative modulatory functions of GIP/GIPR signaling in adult neurons. In complement, we also observed expression of GIP and its receptor in myelinating Schwann cells and oligodendrocytes. Polarized localization of GIPR in the abaxonal Schwann cell membranes, plasma membrane-associated GIPR expression of satellite cells, and ependymal GIPR expression strongly suggests complex cell type-specific functions of GIP and GIPR in the adult nervous system that are presumably mediated by autocrine and paracrine interactions, respectively. Notably, in vivo analyses with GIPR-deficient mice suggest a critical role of GIP/GIPR signal transduction in promoting spontaneous recovery after nerve crush, insofar as traumatic injury of GIPR-deficient mouse sciatic nerve revealed impaired axonal regeneration compared with wild-type mice. © 2009 Wiley-Liss, Inc. [source] Blockade of the 5-HT3 receptor for days causes sustained relief from mechanical allodynia following spinal cord injuryJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2009Yuhua Chen Abstract Chronic neuropathic pain is a frequent, serious outcome of spinal cord injury (SCI) that is highly refractory to treatment. Serotonin can contribute to neuropathic pain after SCI, as suggested by our previous observation that transient blockade of the 5-HT3 receptor by intrathecal injections of the antagonist ondansetron reduces mechanical allodynia after SCI in rats. The current study determined whether intrathecal or intravenous infusion of ondansetron for 3 or 7 days, respectively, could cause sustained blockade of mechanical allodynia at and below the level of a twelfth thoracic clip compression injury in rats. Intrathecal 3-day infusion of ondansetron (2.0 ,g/hr), targeted to the cord rostral to the SCI and commencing at 28 days after SCI, decreased at-level mechanical allodynia by 40% and below-level allodynia by 60% compared with saline-treated rats (controls). This reduction was sustained throughout drug delivery and for 1 day afterward. During the next 3 days, allodynia gradually returned toward the values of saline-treated rats. An initial experiment showed that bolus intravenous injections of ondansetron (20,100 ,g) at 28 days after SCI decreased both at- and below-level allodynia for 90,120 min. Intravenous 7-day infusions (20 ,g/hr), commencing at 28 days after SCI, significantly decreased at-level allodynia by 48% and below-level allodynia by 51% compared with controls. This reduction of allodynia lasted throughout the infusion and for 1,3 days afterward while pain responses gradually approached those of controls. These findings suggest a potential role of 5-HT3 receptor antagonism in the relief of neuropathic pain after SCI in humans. © 2008 Wiley-Liss, Inc. [source] Indole ring orientations of Trp189 in the ground and M intermediate states of bacteriorhodopsin as studied by polarized UV resonance Raman spectroscopy,JOURNAL OF RAMAN SPECTROSCOPY, Issue 1-3 2006Kazuhiro Asakawa Abstract Polarized resonance Raman spectroscopy provides a means for orientation analysis of proteins in aligned samples. Previously, we developed a Raman linear intensity difference (RLID) method to determine the orientations of aromatic amino acid side chains in flow-oriented or membrane-bound proteins. In this study, we have applied the RLID method to Trp189 in bacteriorhodopsin (BR), a transmembrane protein that acts as a light-driven proton pump. Among the eight Trp residues in BR, the Raman spectrum of Trp189 has been extracted by subtracting the spectrum of the Trp189 , Phe mutant from that of wild-type BR. By examining the 251.3-nm-exited polarized resonance Raman intensities of two indole ring vibrations of Trp189, the directions of the La and Bb transition moments have been determined with respect the membrane normal in the light-adapted ground state (BR568) and a photo-excited intermediate (M). Comparison of the orientations of the Trp189 indole ring derived from the La and Bb inclination angles has shown that the indole ring slightly but significantly reorients toward the ionone ring of the retinal chromophore in the M intermediate. The reorientation of Trp189 is consistent with the previous observation that helix F, on which Trp189 is located, undergoes an outward tilt and the hydrophobic interaction of Trp189 increases in the M intermediate. The RLID method combined with 251.3 nm excitation and point mutation is useful for detecting even a small reorientation of a targeted Trp residue. Copyright © 2006 John Wiley & Sons, Ltd. [source] A re-evaluation of the risk factors for the recurrence of primary sclerosing cholangitis in liver allograftsLIVER TRANSPLANTATION, Issue 3 2009Edward Alabraba Previously, we have found that the absence of the colon after liver transplantation (LT) protects the patient from recurrent primary sclerosing cholangitis (rPSC). As our previous observation has not been confirmed in other series, we have reviewed our cohort of patients grafted for primary sclerosing cholangitis (PSC) with greater numbers and longer follow-up to reassess the rate, consequences, and risk factors for rPSC. We collected data on patients who underwent LT for PSC between January 1986 and April 2006. Data were collected for cytomegalovirus status, inflammatory bowel disease status, time of colectomy, type of colectomy, donor-recipient gender mismatch, recipient sex, extended donor criteria (EDC), and donor risk index. Accepted criteria were used to diagnose rPSC. Of a total of 230 consecutive adult patients, 61 (27%) underwent colectomy pre-/peri-LT, and 54 (23.5%) developed rPSC at a median of 4.6 (range, 0.5,12.9) years post-LT. A total of 263 deceased donor grafts were used, and 73 were EDC grafts. A diagnosis of rPSC was made in 61 of the 263 grafts (23%). The recurrence-free patient survival was significantly better (P < 0.05) in patients who underwent pre-/peri-LT colectomy and in those with non-EDC grafts. In conclusion, in this larger cohort of 230 patients and with longer follow-up of 82.5 (range, 0.0,238.6) months [in comparison with the previous report of 152 recipients with a follow-up of 52.8 (range, 1,146) months], we have shown that colectomy remains a significant risk factor for rPSC and that colectomy before and during initial LT for PSC confers a protective effect against rPSC in subsequent graft(s). Moreover, we have shown that EDC grafts are also a significant risk factor for rPSC. Liver Transpl 15:330,340, 2009. © 2009 AASLD. [source] Binding of response regulator DegU to the aprE promoter is inhibited by RapG, which is counteracted by extracellular PhrG in Bacillus subtilisMOLECULAR MICROBIOLOGY, Issue 6 2003Mitsuo Ogura Summary We screened the putative rap-phr (response regulator aspartyl-phosphate phosphatase- phosphatase regulator) systems identified in the Bacillus subtilis genome for a rap gene that affects aprE (alkaline protease gene) expression by using a multicopy plasmid. We found that rapG was involved in the regulation of aprE, which belongs to the regulon of DegU, the response regulator of the DegS-DegU two-component system. Disruption of rapG and phrG resulted in enhancement and reduction of aprE-lacZ expression, respectively, suggesting that PhrG inhibits RapG activity. Addition of 1,30 nM of a synthetic pentapeptide (PhrG; NH2 -EKMIG-COOH) to the phrG disruptant completely rescued aprE-lacZ expression, indicating that the PhrG peptide is indeed involved in aprE-lacZ expression. Surprisingly, either introduction of multicopy phrG or addition of the PhrG peptide at high concentrations (100,300 nM) to the phrG cells decreased aprE-lacZ expression. These results are reminiscent of the previous observation that at higher concentrations the PhrC peptide inhibits srfA-lacZ expression directed by ComA, the regulator of the ComP-ComA two-component system. Because the Rap proteins belong to a family of aspartyl protein phosphatases, we tried to investigate the possible influence of RapG on dephosphorylation of DegU-P (phosphorylated DegU) in vitro. RapG, however, did not affect dephosphorylation of DegU-P under the adopted experimental conditions. Therefore, we hypothesized that RapG might inhibit the binding activity of DegU to the target promoters. We analysed the interaction of DegU and RapG using the aprE promoter and another target, a comK promoter. Gel shift analysis revealed that RapG served as the inhibitor of DegU binding to the promoter regions of aprE and comK and that this inhibition was counteracted by the PhrG peptide. [source] Epidermal growth factor-dependent enhancement of axonal regeneration in the pond snail Lymnaea stagnalis: Role of phagocyte survivalTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 4 2005Petra M. Hermann Abstract Peripheral nerve injury triggers complex responses from neuronal as well as from multiple nonneuronal cell types. These responses are coordinated by a wide spectrum of secreted and nonsecreted factors, including growth factors, cytokines, and cell adhesion molecules. These molecules originate from different sources and act both locally at the site of injury as well as centrally at the location of the neuronal cell bodies. One of the signal systems frequently implicated in this process is the epidermal growth factor (EGF) family and its receptors. Expression of members of this family as well as that of EGF-receptors is upregulated in different cell types after peripheral nerve injury. However, the functional significance of this response is unclear. Using a simple invertebrate model system (Lymnaea stagnalis), the present study implicates the EGF/EGF-receptor system in the survival of ionized calcium-binding adaptor molecule 1 (Iba1)-positive phagocytes that reside in the nervous system. We show that inhibiting the EGF-signaling pathway enhances cell death in this type of cell, an effect paralleled by a substantial reduction in axonal regeneration. Therefore, complementing our previous observation that Lymnaea EGF provides trophic support to axotomized neurons, the present results emphasize the significance of nonneuronal actions of EGF receptor ligands in axonal regeneration. Thus, we add a novel perspective to the ongoing discussion on the functional significance of the EGF signaling system in the injury responses of the nervous system. J. Comp. Neurol. 492:383,400, 2005. © 2005 Wiley-Liss, Inc. [source] Changes in human EEG alpha activity following exposure to two different pulsed magnetic field sequencesBIOELECTROMAGNETICS, Issue 1 2009C.M. Cook Abstract The present study investigates the effects of a weak (±200 µTpk), pulsed, extremely low frequency magnetic field (ELF MF) upon the human electroencephalogram (EEG). We have previously determined that exposure to pulsed ELF MFs can affect the EEG, notably the alpha frequency (8,13 Hz) over the occipital,parietal region of the scalp. In the present study, subjects (n,=,32) were exposed to two different pulsed MF sequences (1 and 2, used previously) that differed in presentation rate, in order to examine the effects upon the alpha frequency of the human EEG. Results suggest that compared to sham exposure, alpha activity was lowered over the occipital,parietal regions of the brain during exposure to Sequence 1, while alpha activity over the same regions was higher after Sequence 2 exposure. These effects occurred after approximately 5 min of pulsed MF exposure. The results also suggest that a previous exposure to the pulsed MF sequence determined subjects' responses in the present experiment. This study supports our previous observation of EEG changes after 5 min pulsed ELF MF exposure. The results of this study are also consistent with existing EEG experiments of ELF MF and mobile phone effects upon the brain. Bioelectromagnetics 30:9,20, 2009. © 2008 Wiley-Liss, Inc. [source] Selection of a Pentameric Host in the Host,Guest Complexes {[{[P(,-NtBu)]2(,-NH)}5],I},[Li(thf)4]+ and [{[P(,-NtBu)]2(,-NH)}5],HBr,THFCHEMISTRY - A EUROPEAN JOURNAL, Issue 23 2004Felipe García Abstract The structures of the host,guest complexes {[{[P(,-NtBu)]2(,-NH)}5]I},,[Li(thf)4]+ [2,I{Li(thf)4}] and [{[P(,-NtBu)]2(,-NH)}5],HBr,THF (2,HBr,THF) show that increased distortion of the framework of the pentameric macrocycle [{[P(,-NtBu)]2(,-NH)}5] (2) occurs with the larger halide ions. Theoretical studies show that the thermodynamic stabilities of the model host,guest anions [2,X], (X=Cl, Br, I) are in the order Cl,,Br,>I,, that is, the reverse of the templating trend observed experimentally. These studies support the view that the selection of the pentamer 2 over the tetramer [{[P(,-NtBu)]2(,-NH)}4] (1) is kinetically controlled, a conclusion which is also consistent with the previous observation that the frameworks of 1 and 2 are not in dynamic equilibrium with each other. [source] Interaction of Ru(II) Complex with Yeast tRNA Studied by Isothermal Titration CalorimetryCHINESE JOURNAL OF CHEMISTRY, Issue 6 2005Xu Hong Abstract The interaction of metal complex with RNA has been studied by isothermal titration calorimetry (ITC) for the first time. ITC experiments show that complex [Ru(phen)2MPIP]2+ {phen=1,10-phenanthroline, MPIP=2-(4-methylphenyl)imidazo[4,5- f]-1,10-phenanthroline} interacts with yeast tRNA in terms of a model for a single set of identical sites through intercalation, which is consistent with our previous observation obtained from spectroscopic methods, and this binding process was driven by a moderately favorable enthalpy decrease in combination with a moderately favorable entropy increase, suggesting that ITC is an effective method for deep studying the interactions of metal complexes with RNA. [source] NEW INSIGHT INTO THE SIGNALLING PATHWAYS OF HEAT STRESS-INDUCED MYOCARDIAL PRECONDITIONING: PROTEIN KINASE C, TRANSLOCATION AND HEAT SHOCK PROTEIN 27 PHOSPHORYLATIONCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 3 2004Claire Arnaud SUMMARY 1.,Heat stress (HS) is known to induce delayed preconditioning against myocardial infarction 24 h later, but the exact signalling pathway of this response remains to be elucidated. In previous studies, we have shown evidence for the implication of protein kinase C (PKC) and p38 mitogen-activated protein kinase (MAPK) in the HS-induced reduction in infarct size. Furthermore, in their phosphorylated state, small heat shock proteins (Hsp27) seem to confer cytoskeletal protection. In the present study, we sought to determine the effect of HS on the subcellular distribution of PKC isoforms and on Hsp27 phosphorylation. 2.,Rats were subjected to either HS (42°C for 15 min; HS group) or sham anaesthesia (sham group) before their hearts were excised. Myocardial tissue extracts obtained 20 min or 24 h after HS were processed for western blot analysis. 3.,In the HS group, PKC, translocated from the cytosolic to the particulate fraction (4426 ± 128 vs 6258 ± 316 arbitrary units; P = 0.002). Chelerythrine (5 mg/kg, i.p.), a PKC inhibitor, abolished this translocation. Western blot analysis of Hsp27 24 h after HS showed a marked increase in protein expression and phosphorylation in the particulate fraction. 4.,In the present study, we have shown that HS induces the translocation of PKC, from the cytosolic to the particulate fraction. Along with our previous observation that PKC is a trigger of HS-induced myocardial preconditioning, the results of the present study suggest an important role of the , isoform of PKC in this cardioprotective mechanism. Furthermore, we have also demonstrated that the cytoprotective protein Hsp27 is phosphorylated following HS. Therefore, we can conclude that PKC and MAPK/Hsp27 are involved in the signalling pathway of HS-induced cardioprotection. [source] Characteristics of respiratory syncytial virus-related apnoea in three infantsACTA PAEDIATRICA, Issue 6 2004M Rayyan Apnoea is a common sign in respiratory syncytial virus (RSV) infections in young infants and can be the first presentation of an acquired RSV infection. We describe polysomnographic recordings of three infants revealing prolonged RSV-related apnoea before RSV infection was diagnosed. The apnoeas were of central origin. The caregivers had not noted any apparent life-threatening events (ALTE) prior to the polysomnography. Cardiorespiratory monitoring after the acute infection did not reveal any further apnoeas. Conclusion: Central, prolonged apnoea can be the first sign of an acquired RSV infection in young infants in the absence of other respiratory symptoms and without any previous observation of apnoea by the caregivers. [source] Inductive Inference by Using Information CompressionCOMPUTATIONAL INTELLIGENCE, Issue 2 2003Ben Choi Inductive inference is of central importance to all scientific inquiries. Automating the process of inductive inference is the major concern of machine learning researchers. This article proposes inductive inference techniques to address three inductive problems: (1) how to automatically construct a general description, a model, or a theory to describe a sequence of observations or experimental data, (2) how to modify an existing model to account for new observations, and (3) how to handle the situation where the new observations are not consistent with the existing models. The techniques proposed in this article implement the inductive principle called the minimum descriptive length principle and relate to Kolmogorov complexity and Occam's razor. They employ finite state machines as models to describe sequences of observations and measure the descriptive complexity by measuring the number of states. They can be used to draw inference from sequences of observations where one observation may depend on previous observations. Thus, they can be applied to time series prediction problems and to one-to-one mapping problems. They are implemented to form an automated inductive machine. [source] Nitric oxide, superoxide and renal blood flow autoregulation in SHR after perinatal L -arginine and antioxidantsACTA PHYSIOLOGICA, Issue 4 2007M. P. Koeners Abstract Aim:, Nitric oxide (NO) and superoxide are considered to be regulatory in renal blood flow (RBF) autoregulation, and hence may contribute to development of hypertension. To extend our previous observations that dynamic NO release is impaired in the spontaneously hypertensive rat (SHR) we investigated, firstly, if superoxide dependency of RBF autoregulation is increased in SHR and, secondly, if the beneficial effect of perinatal supplementation in SHR is partly as a result of early correction of RBF autoregulation. We hypothesized that perinatal supplementation by restoring dynamic NO release and/or decreasing superoxide dependency and would improve life-long blood pressure regulation. Methods:, Autoregulation was studied using stepwise reductions in renal perfusion pressure in anaesthetized male SHR, SHR perinatally supplemented with arginine and antioxidants (SHRsuppl) and Wistar-Kyoto (WKY), prior to and during i.v. N, -nitro- l -arginine (NO synthase inhibitor) or tempol (superoxide dismutase mimetic). Results:, Spontaneously hypertensive rat displayed a wider operating range of RBF autoregulation as compared with WKY (59 ± 4 vs. 33 ± 2 mmHg, respectively; P < 0.01). Perinatal supplementation in SHR decreased mean arterial pressure, renal vascular resistance and the operating range of RBF autoregulation (43 ± 3 mmHg; P < 0.01). In addition autoregulation efficiency decreased. RBF autoregulation characteristics shifted towards those of normotensive WKY. However, dynamic NO release was still impaired and no clear differences in superoxide dependency in RBF autoregulation between groups was observed. Conclusion:, Perinatal supplements shifted RBF autoregulation characteristics of SHR towards WKY, although capacity of the SHRsuppl kidney to modulate NO production to shear stress still seems impaired. The less strictly controlled RBF as observed in perinatally supplemented SHR could result in an improved long-term blood pressure control. This might partly underlie the beneficial effects of perinatal supplementation. [source] High speed sliding of axonemal microtubules produced by outer arm dyneinCYTOSKELETON, Issue 2 2005Raviraja N. Seetharam Abstract To study dynein arm activity at high temporal resolution, axonemal sliding was measured field by field for wild type and dynein arm mutants of Tetrahymena thermophila. For wt SB255 cells, when the rate of data acquisition was 60 fps, about 5× greater than previously published observations, sliding was observed to be discontinuous with very high velocity sliding (average 196 ,m/sec) for a few msec (1 or 2 fields) followed by a pause of several fields. The sliding velocities measured were an order of magnitude greater than rates previously measured by video analysis. However, when the data were analyzed at 12 fps for the same axonemes, consistent with previous observations, sliding was linear as the axonemes extended several times their original length with an average velocity of ,10 ,m/sec. The pauses or stops occurred at approximately 200 and 300% of the initial length, suggesting that dynein arms on one axonemal doublet were initially active to the limit of extension, and then the arms on the next doublet became activated. In contrast, in a mutant where OADs are missing, sliding observed at 60 fps was continuous and slow (5 ,m/sec), as opposed to the discontinuous high-velocity sliding of SB255 and of the mutant at the permissive temperature where OADs are present. High-velocity step-wise sliding was also present in axonemes from an inner arm dynein mutant (KO6). These results indicate that the high-speed discontinuous pattern of sliding is produced by the mechanochemical activity of outer arm dynein. The rate of sliding is consistent with a low duty ratio of the outer arm dynein and with the operation of each arm along a doublet once per beat. Cell Motil. Cytoskeleton 60:96,103, 2005. © 2004 Wiley-Liss, Inc. [source] Platelet activation and secretion in patients with major depression, thoracic aortic atherosclerosis, or renal dialysis treatmentDEPRESSION AND ANXIETY, Issue 3 2002Dominique L. Musselman M.D., M.S. Abstract Relatively little is known concerning the magnitude of alterations of platelet activation and secretion markers of patients with major depression when compared to patients at increased risk for, or with current, clinically significant atherosclerosis. Markers of in vivo platelet stimulation and secretion were measured under basal conditions in normal comparison subjects (n = 12) and three patient groups: patients diagnosed with DSM-IV major depression (n = 15), dialysis-dependent patients (n = 12), and patients with severe thoracic aortic atherosclerosis (n = 10). In comparison to normal comparison subjects, depressed patients and patients with thoracic aortic atherosclerosis exhibited the greatest platelet stimulation as detected by increased anti-LIBS platelet binding. Dialysis-dependent patients exhibited the highest plasma concentrations of the renally-excreted platelet-specific secretion protein, ,-thromboglobulin. This study extends previous observations of increased platelet activation in patients with major depression and documents similar alterations in patients with transesophageal echocardiography (TEE)-documented thoracic aortic atherosclerosis. Future studies will determine whether the magnitude of platelet stimulation and secretion in patients with comorbid depression and atherosclerotic aortic disease is greater than that observed in nondepressed patients with atherosclerotic aortic disease or major depression alone. These findings provide further evidence for either increased platelet activation and/or intrinsic heightened platelet reactivity as one of the biological substrates underlying the increased risk of depressed patients for cardiovascular disease. Depression and Anxiety 15:91,101, 2002. © 2002 Wiley-Liss, Inc. [source] Spatiotemporal distribution of heparan sulfate epitopes during myogenesis and synaptogenesis: A study in developing mouse intercostal muscleDEVELOPMENTAL DYNAMICS, Issue 1 2002Guido J. Jenniskens Abstract Formation of a basal lamina (BL) ensheathing developing skeletal muscle cells is one of the earliest events in mammalian skeletal muscle myogenesis. BL-resident heparan sulfate proteoglycans have been implicated in various processes during myogenesis, including synaptic differentiation. However, attention has focused on the proteoglycan protein core, ignoring the glycosaminoglycan moiety mainly because of a lack of appropriate tools. Recently, we selected a panel of anti,heparan sulfate antibodies applied here to study the spatiotemporal distribution of specific heparan sulfate (HS) epitopes during myogenesis. In mouse intercostal muscle at embryonic day (E14), formation of acetylcholine receptor clusters at synaptic sites coincides with HS deposition. Although some HS epitopes show a general appearance throughout the BL, one epitope preferably clusters at synaptic sites but does so only from E16 onward. During elongation and maturation of primary myotubes, a process preceding secondary myotube development, significant changes in the HS epitope constitution of both synaptic and extrasynaptic BL were observed. As a whole, the data presented here strengthen previous observations on developmental regulation by BL components, and add to the putative roles of specific HS epitopes in myogenesis and synaptogenesis. © 2002 Wiley-Liss, Inc. [source] Drosophila RSK negatively regulates bouton number at the neuromuscular junctionDEVELOPMENTAL NEUROBIOLOGY, Issue 4 2009Matthias Fischer Abstract Ribosomal S6 kinases (RSKs) are growth factor-regulated serine-threonine kinases participating in the RAS-ERK signaling pathway. RSKs have been implicated in memory formation in mammals and flies. To characterize the function of RSK at the synapse level, we investigated the effect of mutations in the rsk gene on the neuromuscular junction (NMJ) in Drosophila larvae. Immunostaining revealed transgenic expressed RSK in presynaptic regions. In mutants with a full deletion or an N-terminal partial deletion of rsk, an increased bouton number was found. Restoring the wild-type rsk function in the null mutant with a genomic rescue construct reverted the synaptic phenotype, and overexpression of the rsk -cDNA in motoneurons reduced bouton numbers. Based on previous observations that RSK interacts with the Drosophila ERK homologue Rolled, genetic epistasis experiments were performed with loss- and gain-of-function mutations in Rolled. These experiments provided evidence that RSK mediates its negative effect on bouton formation at the Drosophila NMJ by inhibition of ERK signaling. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 2009 [source] Lesion-induced neurogenesis in the hypothalamus is involved in behavioral recovery in adult ring dovesDEVELOPMENTAL NEUROBIOLOGY, Issue 6 2006Gang Chen Abstract Although neurogenesis in the brain of adult vertebrates is region dependent, lesion induces generation of new neurons in non-neurogenic brain regions. These findings raise the question of the role of new neurons in brain repair and functional recovery. We addressed this question by applying previous observations that electrolytic lesion induced neurogenesis in the ventromedial nucleus (VMN) of the hypothalamus in adult ring doves. Such lesions disrupted the male's courtship behavior, which could be reinstated after rehabilitation with a female. We investigated whether lesion-induced newborn neurons in the VMN facilitate the recovery of courtship behavior in the lesioned birds. We conducted systematic observations of cytological, morphological, and neuroanatomical changes in the lesioned VMN, and concurrently we monitored behavioral changes. Using a multitude of specific cell markers, we found a well-circumscribed cellular zone that proliferated actively. This highly proliferative zone initially appeared along the periphery of the lesion site, where cells had high levels of expression of neuronal, glial, and neurovascular markers. As newborn neurons matured at the lesion site, the necrosis gradually decreased, whereas a downsized proliferative zone relocated to a region ventral to the VMN. Some of the mature neurons were found to project to the midbrain vocal nuclei. Restoration of these projection neurons coincided with the recovery of courtship vocalization. Finally, we found that a social factor, that is, when the male doves were cohoused with a mate, facilitated neurogenesis and behavioral recovery. These results suggest that lesion-induced neurogenesis contributes to behavioral recovery in adult animals. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 [source] Circulating insulin antibodies: influence of continuous subcutaneous or intraperitoneal insulin infusion, and impact on glucose controlDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 6 2009R. P. Radermecker Abstract The purification of animal insulin preparations and the use of human recombinant insulin have markedly reduced the incidence, but not completely suppressed, the development of anti-insulin antibodies (IAs). Advances in technologies concerning the mode of delivery of insulin, i.e. continuous subcutaneous insulin infusion (CSII), continuous peritoneal insulin infusion (CPII) and more recently inhaled insulin administration, appear to significantly increase circulating levels of immunoglobulin G (IgG) anti-IAs in diabetic patients. However, the increase is usually moderate and mostly transient as compared to previous observations with poorly purified animal insulin preparations. The clinical impact of these circulating anti-IAs remains unclear. Nevertheless, several studies have suggested that antibodies could retard insulin action, leading to a worsening of postprandial hyperglycaemia and/or serve as a carrier, thus leading to unexpected hypoglycaemia. CPII may be associated with more marked and sustained increase in IAs levels, possibly related to the use of an unstable insulin and the formation of immunogenic aggregates of insulin. The possible clinical consequences of these high levels of IAs remain to be evaluated because a low-glucose morning syndrome or severe insulin resistance with ketone bodies production have been reported in some cases. In conclusion, even if CSII and CPII may promote the development of circulating IAs, this increase does not lead to immunological insulin resistance, compared to that previously described with animal non-purified insulin preparations, and seems to have only marginal influence on blood glucose control or complications in most diabetic patients. Copyright © 2009 John Wiley & Sons, Ltd. [source] A dendrobranchiate, Peisos petrunkevitchi (Decapoda, Sergestidae), with reptant-like sperm: a spermiocladistic assessmentACTA ZOOLOGICA, Issue 2 2004Marcelo A. Scelzo Abstract The spermatozoon of Peisos petrunkevitchi differs significantly from those of any of the investigated dendrobranchiates in the anterior fusiform acrosome, lacking a spike, and embedded in (instead of capping) the nuclear region. In contrast, the position of the acrosome and the internal arrangement of its contents, as well as the apomorphic presence of a pair of centrioles (absent in all known dendrobranchiate spermatozoa) at the base of the acrosomal perforatorium, indicate a close affinity between this sperm plan and that found in reptants, especially anomurans and brachyurans. Based on the present and previous observations on decapod spermatozoal ultrastructure, we review the phylogeny of dendrobranchiate spermatozoa in the perspective of most recent phylogenetic analyses of malacostracan crustaceans. [source] Detection of microbial biomass by intact polar membrane lipid analysis in the water column and surface sediments of the Black SeaENVIRONMENTAL MICROBIOLOGY, Issue 10 2009Florence Schubotz Summary The stratified water column of the Black Sea produces a vertical succession of redox zones, stimulating microbial activity at the interfaces. Our study of intact polar membrane lipids (IPLs) in suspended particulate matter and sediments highlights their potential as biomarkers for assessing the taxonomic composition of live microbial biomass. Intact polar membrane lipids in oxic waters above the chemocline represent contributions of bacterial and eukaryotic photosynthetic algae, while anoxygenic phototrophic bacteria and sulfate-reducing bacteria comprise a substantial amount of microbial biomass in deeper suboxic and anoxic layers. Intact polar membrane lipids such as betaine lipids and glycosidic ceramides suggest unspecified anaerobic bacteria in the anoxic zone. Distributions of polar head groups and core lipids show planktonic archaea below the oxic zone; methanotrophic archaea are only a minor fraction of archaeal biomass in the anoxic zone, contrasting previous observations based on the apolar derivatives of archaeal lipids. Sediments contain algal and bacterial IPLs from the water column, but transport to the sediment is selective; bacterial and archaeal IPLs are also produced within the sediments. Intact polar membrane lipid distributions in the Black Sea are stratified in accordance with geochemical profiles and provide information on vertical successions of major microbial groups contributing to suspended biomass. This study vastly extends our knowledge of the distribution of complex microbial lipids in the ocean. [source] Comparison of hardness- and chloride-regulated acute effects of sodium sulfate on two freshwater crustaceansENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 4 2007David John Soucek Abstract Based on previous observations that hardness (and potentially chloride) influences sodium sulfate toxicity, the objective of the current study was to quantify the influence of both chloride and water hardness on acute toxicity to Hyalella azteca and Ceriodaphnia dubia. In addition, observed toxicity data from the present study were compared to toxicity predictions by the salinity/toxicity relationship (STR) model. Hardness had a strong influence on sulfate toxicity that was similar for both crustaceans, and nearly identical median lethal concentration (LC50)/hardness slopes were observed for the two species over the tested range. Chloride had a strong but variable influence on sulfate acute toxicity, depending on the species tested and the concentration range. At lower chloride concentrations, LC50s for H. azteca strongly were correlated positively with chloride concentration, although chloride did not affect the toxicity of sodium sulfate to C. dubia. The opposite trend was observed over the higher range of chloride concentrations where there was a negative correlation between chloride concentration and sulfate LC50 for both species. The widely ranging values for both species and a high correlation between LC50s in terms of sulfate and conductivity suggested that, whether based on sulfate, conductivity, or total dissolved solids (TDS), attempts at water quality standard development should incorporate the fact that water quality parameters such as hardness and chloride strongly influence the toxicity of high TDS solutions. The STR model predicted toxicity to C. dubia relatively well when chloride was variable and hardness fixed at approximately 100 mg/L; however, the model did not account for the protective effect of hardness on major ion/TDS toxicity. [source] Relationship between lysosomal membrane destabilization and chemical body burden in eastern oysters (Crassostrea virginica) from Galveston Bay, Texas, USAENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 6 2002Hyun-Min Hwang Abstract Lysosomal destabilization was measured by using hemocytes of eastern oysters (Crassostrea virginica) collected along a chemical concentration gradient in Galveston Bay, Texas, USA. Results of the lysosomal response were compared to concentrations of organic compounds and trace elements in oyster tissue. Concentrations (on a dry-wt basis) ranged from 288 to 2,390 ng/g for polycyclic aromatic hydrocarbons (PAHs), 38 to 877 ng Sn/g for tri- n -butyltin (TBT), 60 to 562 ng/g for polyclorinated biphenyls (PCBs), and 7 to 71 ng/g for total DDT. Trace element concentrations (on a dry-wt basis) ranged from 1.1 to 4.0 ,g/g for Cd, 105 to 229 ,g/g for Cu, 212 to 868 ,g/g for Al, and 1,200 to 8,180 ,g/g for Zn. The percentage of destabilized lysosomes ranged from 34 to 81%. A significant positive correlation (p < 0.05) was observed between lysosomal destabilization and body burden of organic compounds (PAHs, PCBs, TBT, and chlorinated pesticides). No significant correlation was found between metal concentrations and lysosomal destabilization. Based on lysosomal destabilization, the study sites in Galveston Bay can be placed in one of three groups: healthy (Hanna Reef and Confederate Bay), moderately damaged (Offats Bayou and Todd's Dump), and highly damaged (Yacht Club and Ship Channel). Lysosomal destabilization that is consistent with toxic chemical body burdens supports previous observations that lysosomal membranes are damaged by toxic chemicals and indicates that this method can serve as an early screening tool to assess overall ecosystem health by using oysters. [source] Expression of zonula occludens-1 (ZO-1) and the transcription factor ZO-1-associated nucleic acid-binding protein (ZONAB),MsY3 in glial cells and colocalization at oligodendrocyte and astrocyte gap junctions in mouse brainEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2005Mihai C. Penes Abstract The PDZ domain-containing protein zonula occludens-1 (ZO-1) interacts with several members of the connexin (Cx) family of gap junction-forming proteins and has been localized to gap junctions, including those containing Cx47 in oligodendrocytes. We now provide evidence for ZO-1 expression in astrocytes in vivo and association with astrocytic connexins by confocal immunofluorescence demonstration of ZO-1 colocalization with astrocytic Cx30 and Cx43, and by ZO-1 coimmunoprecipitation with Cx30 and Cx43. Evidence for direct interaction of Cx30 with ZO-1 was obtained by pull-down assays that indicated binding of Cx30 to the second of the three PDZ domains in ZO-1. Further, we investigated mouse Y-box transcription factor MsY3, the canine ortholog of which has been termed ZO-1-associated nucleic acid-binding protein (ZONAB) and previously reported to interact with ZO-1. By immunofluorescence using specific antimouse ZONAB antibody, ZONAB was found to be associated with oligodendrocytes throughout mouse brain and spinal cord, and to be colocalized with oligodendrocytic Cx47 and Cx32 as well as with astrocytic Cx43. Our results extend the CNS cell types that express the multifunctional protein ZO-1, demonstrate an additional connexin (Cx30) that directly interacts with ZO-1, and show for the first time the association of a transcription factor (ZONAB) with ZO-1 localized to oligodendrocyte and astrocyte gap junctions. Given previous observations that ZONAB and ZO-1 in combination regulate gene expression, our results suggest roles of glial gap junction-mediated anchoring of signalling molecules in a wide variety of glial homeostatic processes. [source] Acute signalling responses to intense endurance training commenced with low or normal muscle glycogenEXPERIMENTAL PHYSIOLOGY, Issue 2 2010Wee Kian Yeo We have previously demonstrated that well-trained subjects who completed a 3 week training programme in which selected high-intensity interval training (HIT) sessions were commenced with low muscle glycogen content increased the maximal activities of several oxidative enzymes that promote endurance adaptations to a greater extent than subjects who began all training sessions with normal glycogen levels. The aim of the present study was to investigate acute skeletal muscle signalling responses to a single bout of HIT commenced with low or normal muscle glycogen stores in an attempt to elucidate potential mechanism(s) that might underlie our previous observations. Six endurance-trained cyclists/triathletes performed a 100 min ride at ,70% peak O2 uptake (AT) on day 1 and HIT (8 × 5 min work bouts at maximal self-selected effort with 1 min rest) 24 h later (HIGH). Another six subjects, matched for fitness and training history, performed AT on day 1 then 1,2 h later, HIT (LOW). Muscle biopsies were taken before and after HIT. Muscle glycogen concentration was higher in HIGH versus LOW before the HIT (390 ± 28 versus 256 ± 67 ,mol (g dry wt),1). After HIT, glycogen levels were reduced in both groups (P < 0.05) but HIGH was elevated compared with LOW (229 ± 29 versus 124 ± 41 ,mol (g dry wt),1; P < 0.05). Phosphorylation of 5,AMP-activated protein kinase (AMPK) increased after HIT, but the magnitude of increase was greater in LOW (P < 0.05). Despite the augmented AMPK response in LOW after HIT, selected downstream AMPK substrates were similar between groups. Phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) was unchanged for both groups before and after the HIT training sessions. We conclude that despite a greater activation AMPK phosphorylation when HIT was commenced with low compared with normal muscle glycogen availability, the localization and phosphorylation state of selected downstream targets of AMPK were similar in response to the two interventions. [source] | |||||||||||||||||||||||||||||||||||||||||||||||||