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Terminal Portion (terminal + portion)
Selected AbstractsEffects of acute vagal nerve stimulation on the early passive electrical changes induced by myocardial ischaemia in dogs: heart rate-mediated attenuationEXPERIMENTAL PHYSIOLOGY, Issue 8 2008Carlos L. Del Rio Parasympathetic activity during acute coronary artery occlusion (CAO) can protect against ischaemia-induced malignant arrhythmias; nonetheless, the mechanism mediating this protection remains unclear. During CAO, myocardial electrotonic uncoupling is associated with autonomically mediated immediate (i.e. type 1A) arrhythmias and can modulate pro-arrhythmic dispersion of repolarization. Therefore, the effects of acutely enhanced or decreased cardiac parasympathetic activity on early electrotonic coupling during CAO, as measured by myocardial electrical impedance (MEI), were investigated. Anaesthetized dogs were instrumented for MEI measurements, and left circumflex coronary arterial occlusions were performed in intact (CTRL) and vagotomized (VAG) animals. The CAO was followed by either vagotomy (CTRL) or vagal nerve stimulation (VNS, 10 Hz, 10 V) in the VAG dogs. Vagal nerve stimulation was studied in two additional sets of animals. In one set heart rate (HR) was maintained by pacing (220 beats min,1), while in the other set bilateral stellectomy preceded CAO. The MEI increased after CAO in all animals. A larger MEI increase was observed in vagotomized animals (+85 ± 9 ,, from 611 ± 24 ,, n= 16) when compared with intact control dogs (+43 ± 5 ,, from 620 ± 20 ,, n= 7). Acute vagotomy during ischaemia abruptly increased HR (from 155 ± 11 to 193 ± 15 beats min,1) and MEI (+12 ± 1.1 ,, from 663 ± 18 ,). In contrast, VNS during ischaemia (n= 11) abruptly reduced HR (from 206 ± 6 to 73 ± 9 beats min,1) and MEI (,16 ± 2 ,, from 700 ± 44 ,). These effects of VNS were eliminated by pacing but not by bilateral stellectomy. Vagal nerve stimulation during CAO also attenuated ECG-derived indices of ischaemia (e.g. ST segment, 0.22 ± 0.03 versus 0.15 ± 0.03 mV) and of rate-corrected repolarization dispersion [terminal portion of T wave (TPEc), 84.5 ± 4.2 versus 65.8 ± 5.9 ms; QTc, 340 ± 8 versus 254 ± 16 ms]. Vagal nerve stimulation during myocardial ischaemia exerts negative chronotropic effects, limiting early ischaemic electrotonic uncoupling and dispersion of repolarization, possibly via a decreased myocardial metabolic demand. [source] Plk3 inhibits pro-apoptotic activity of p73 through physical interaction and phosphorylationGENES TO CELLS, Issue 7 2009Meixiang Sang Plk3, one of Polo-like kinase family members, is involved in the regulation of cell cycle progression and DNA damage response. In this study, we found that Plk3 inhibits pro-apoptotic activity of p73 through physical interaction and phosphorylation. During cisplatin (CDDP)-mediated apoptosis, Plk3 was transcriptionally induced, whereas its protein level was kept at basal level, suggesting that Plk3 might rapidly degrade in response to CDDP. Immunoprecipitation and in vitro pull-down experiments demonstrated that Plk3 interacts with p73. Luciferase reporter assays and RT-PCR experiments revealed that Plk3 inhibits p73-mediated transcriptional activity. Consistent with these results, pro-apoptotic activity of p73 was blocked by Plk3. Additionally, Plk3 decreased the stability of p73. Intriguingly, kinase-deficient Plk3 failed to inhibit p73 function, indicating that kinase activity of Plk3 is required for Plk3-mediated inhibition of p73. Indeed, in vitro kinase reaction showed that NH2 -terminal portion of p73 is phosphorylated by Plk3. In accordance with these observations, knocking down of Plk3 increased the stability of p73 and promoted CDDP-mediated apoptosis in association with up-regulation of p73. Collectively, our present findings suggest that Plk3 plays an important role in the regulation of cell fate determination in response to DNA damage through the inhibition of p73. [source] Accumulation of amyloid-, protein in exocrine glands of transgenic mice overexpressing a carboxyl terminal portion of amyloid protein precursorINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2000Ken-Ichiro Fukuchi Amyloid-, protein (A,) and its precursor (,PP) play important roles in the pathogenesis of Alzheimer disease and inclusion-body myositis. In humans, A, deposits are found in brain, skeletal muscle, and skin. Therefore, we have investigated possible A, deposits in multiple tissues of two transgenic mouse lines overexpressing the signal plus A,-bearing 99-amino acid carboxyl terminal sequences of ,PP under the control of a cytomegalovirus enhancer/,-actin promoter. One of the lines developed A,-immunoreactive intracellular deposits consistently in the pancreas and lacrimal gland, and occasionally in gastric, DeSteno's, and lingual glands. Although the A, deposits increased during ageing and degenerative changes of the tissues were observed, little or no extracellular A, deposits were observed up to the age of 25 months. These lines of transgenic mice are useful for studying the molecular mechanisms of development and clearance of intracellular A, deposits. [source] Structure,function relationship studies of PTH(1,11) analogues containing sterically hindered dipeptide mimeticsJOURNAL OF PEPTIDE SCIENCE, Issue 8 2007Nereo Fiori Abstract The N -terminal 1,34 fragment of parathyroid hormone (PTH) is fully active in vitro and in vivo and reproduces all biological responses characteristic of the native intact PTH. In order to develop safer and non-parenteral PTH-like bone anabolic agents, we have studied the effect of introducing conformationally constrained dipeptide mimetics into the N -terminal portion of PTH in an effort to generate miniaturized PTH-mimetics. To this end, we have synthesized and conformationally and biologically characterized PTH(1,11) analogues containing 3R -carboxy-6S -amino-7,5-bicyclic thiazolidinlactam (7,5-bTL), a rigidified dipeptide mimetic unit. The wild type sequence of PTH(1,11) is H-Ser-Val-Ser-Glu-Ile-Gln-Leu-Met-His-Asn-Leu-NH2. The following pseudo-undecapeptides were prepared: [Ala1, 7,5-bTL3, 4, Nle8, Arg11]hPTH(1,11)NH2 (I); [Ala1, 7,5-bTL6, 7, Nle8, Arg11]hPTH(1,11)NH2 (II); [Ala1, Nle8, 7,5-bTL9, 10, Arg11]hPTH(1,11)NH2 (III). In aqueous solution containing 20% TFE, only analogue I exhibited the typical CD pattern of the ,-helical conformation. NMR experiments and molecular dynamics calculations located the ,-helical stretch in the sequence Ile5 -His9. The dipeptide mimetic unit 7,5-bTL induces a type III ,-turn, occupying the positions i , 1 and i of the turn. Analogue II exhibited an equilibrium between a type I ,-turn and an ,-helix, and analogue III did not show any ordered structure. Biological tests revealed poor activity for all analogues (EC50 > 0.1 mM). Apparently, the relative side-chain orientation of Val2, Ile5 and Met8 can be critical for effective analogue-receptor interaction. Considering helicity as an essential property to obtain active PTH agonists, one must decorate the correctly positioned dipeptide mimetic azabicycloalkane scaffold with substitutions corresponding to the displaced amino acids. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd. [source] Conformation of N-terminal HIV-1 tat (fragment 1,9) peptide by NMR and MD simulationsJOURNAL OF PEPTIDE SCIENCE, Issue 11 2001Meena Kanyalkar Abstract The N -terminal portion of HIV-1 Tat covering residues 1,9 is a competitive inhibitor of dipeptidyl peptidase IV (DP IV). We have used 1H NMR techniques, coupled with molecular dynamics methods, to determine the conformation of this peptide in the three diverse media: DMSO-d6, water (pH 2.7) and 40% HFA solution. The results indicate that in both DMSO-d6 and HFA the peptide has a tendency to acquire a type I ,-turn around the segment Asp5 -Pro6 -Asn7 -Ile8. The N -terminal end is seen to be as a random coil. In water, the structure is best described as a left-handed polyproline type II (PPII) helix for the mid segment region Asp2 to Pro6. The structures obtained in this study have been compared with an earlier report on Tat (1,9). Copyright © 2000 European Peptide Society and John Wiley & Sons, Ltd. [source] Prosaposin-derived peptides enhanced sprouting of sensory neurons in vitro and induced sprouting at motor endplates in vivoJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 3 2000W. Marie Campana Abstract Prosaposin exhibits neurotrophic factor properties that are localized to a 12-amino acid sequence located in the amino terminal portion of the saposin C domain. Prosaptides are peptides derived from the neurotrophic portion of prosaposin; these have been previously reported to be bioactive in neuroblastoma cell lines in vitro. We report that prosaptides were also bioactive in explants of adult primary sensory neurons by dose-dependently increasing both the number (3- to 4-fold) and elongation of these neurites by 50%. Local injection of prosaptides into the gluteus muscle of adult mice also induced sprouting at the motor endplate. Our results indicate that prosaptides are potent neuritogenic factors for both sensory and motor neurons of adult peripheral nerve. [source] Antibody responses to the host-protective Taenia solium oncosphere protein TSOL18 in pigs are directed against conformational epitopesPARASITE IMMUNOLOGY, Issue 6 2010E. ASSANA Summary TSOL18 is a recombinant protein that has been shown in repeated experimental trials to be capable of protecting pigs against challenge infection with the cestode parasite Taenia solium. Antibodies raised by the vaccine are capable of killing the parasite in an in vitro culture and it is believed that antibody and complement-mediated killing of invading parasites is the major protective immune mechanism induced by vaccination with TSOL18. Investigations were undertaken to characterize whether the principal antibody specificities raised by TSOL18 in pigs were against linear or conformational determinants. TSOL18 was expressed in two truncated forms representing either the amino terminal portion or the carboxy terminal portion, with the two truncations overlapping in sequence by 25 amino acids. The original protein (designated TSOL18N,) and the two truncations (TSOL18N, -1 and TSOL18N, -2) were used in inhibition ELISA. TSOL18N, was shown to be capable of completely inhibiting the binding of pig anti-TSOL18N, antibodies to TSOL18N, in ELISA. However, neither TSOL18N, -1 nor TSOL18N, -2, either alone or when combined together, was capable of inhibiting any detectable amount of reactivity of pig anti-TSOL18N, antibodies with TSOL18N,. It is concluded that the dominant antibody specificities, and probably the host-protective specificities, of TSOL18 are conformational epitopes. [source] A contiguous deletion syndrome of X-linked agammaglobulinemia and sensorineural deafnessPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 2 2001Darko Richter Hearing loss in patients with X-linked agammaglobulinemia is often attributed to recurrent infections. However, recent genetic studies suggest a different etiology in some patients. We present three unrelated patients, 6, 9, and 14 years of age, with large deletions of the terminal portion of the Bruton tyrosine kinase (Btk) gene extending 4.2,19 kb beyond the 3, end of the gene. The DNA immediately downstream of the 3, end of Btk contains the deafness-dystonia protein gene (DDP). Mutations in this gene have recently been shown to underlie the Mohr,Tranebjaerg syndrome, which is characterized by sensorineural deafness, dystonia, and mental deficiency. Besides the immunodeficiency, our patients exhibited progressive sensorineural deafness. The clue to an associated hearing problem was delayed development of speech in one patient and post-lingual deafness noticed between the age of 3,4 years in the other two. These patients have not yet exhibited significant associated neurologic deficits. [source] Manipulation of DET1 expression in tomato results in photomorphogenic phenotypes caused by post-transcriptional gene silencingTHE PLANT JOURNAL, Issue 3 2004Ganga Rao Davuluri Summary The tomato HIGH PIGMENT-2 gene encodes an orthologue of the Arabidopsis nuclear protein DE-ETIOLATED 1 (DET1). From genetic analyses it has been proposed that DET1 is a negative regulator of light signal transduction, and recent results indicate that it may control light-regulated gene expression at the level of chromatin remodelling. To gain further understanding about the function of DET1 during plant development, we generated a range of overexpression constructs and introduced them into tomato. Unexpectedly, we only observed phenotypes characteristic of DET1 inactivation, i.e. hyper-responsiveness to light. Molecular analysis indicated in all cases that these phenotypes were a result of suppression of endogenous DET1 expression, due to post-transcriptional gene silencing. DET1 silencing was often lethal when it occurred at relatively early stages of plant development, whereas light hyper-responsive phenotypes were obtained when silencing occurred later on. The appearance of phenotypes correlated with the generation of siRNAs but not DNA hypermethylation, and was most efficient when using constructs with mutations in the DET1 coding sequence or with constructs containing only the 3,-terminal portion of the gene. These results indicate an important function for DET1 throughout plant development and demonstrate that silencing of DET1 in fruits results in increased carotenoids, which may have biotechnological potential. [source] Different portions of the maize root system host Burkholderia cepacia populations with different degrees of genetic polymorphismENVIRONMENTAL MICROBIOLOGY, Issue 1 2000Luigi Chiarini In order to acquire a better understanding of the spatial and temporal variations of genetic diversity of Burkholderia cepacia populations in the rhizosphere of Zea mays, 161 strains were isolated from three portions of the maize root system at different soil depths and at three distinct plant growth stages. The genetic diversity among B. cepacia isolates was analysed by means of the random amplified polymorphic DNA (RAPD) technique. A number of diversity indices (richness, Shannon diversity, evenness and mean genetic distance) were calculated for each bacterial population isolated from the different root system portions. Moreover, the analysis of molecular variance ( amova) method was applied to estimate the genetic differences among the various bacterial populations. Our results showed that, in young plants, B. cepacia colonized preferentially the upper part of the root system, whereas in mature plants, B. cepacia was mostly recovered from the terminal part of the root system. This uneven distribution of B. cepacia cells among different root system portions partially reflected marked genetic differences among the B. cepacia populations isolated along maize roots on three distinct sampling occasions. In fact, all the diversity indices calculated indicated that genetic diversity increased during plant development and that the highest diversity values were found in mature maize plants, in particular in the middle and terminal portions of the root system. Moreover, the analysis of RAPD patterns by means of the amova method revealed highly significant divergences in the degree of genetic polymorphism among the various B. cepacia populations. [source] Differential distribution of Rac1 and Rac3 GTPases in the developing mouse brain: implications for a role of Rac3 in Purkinje cell differentiationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2003Annalisa Bolis Abstract Rac3 is one of the three known Rac GTPases in vertebrates. Rac3 shows high sequence homology to Rac1, and its transcript is specifically expressed in the developing nervous system, where its localization and function are unknown. By using Rac3-specific antibodies, we show that the endogenous Rac3 protein is differentially expressed during mouse brain development, with a peak of expression at times of neuronal maturation and synaptogenesis. Comparison with Rac1 shows clear-cut differences in the overall distribution of the two GTPases in the developing brain, and in their subcellular distribution in regions of the brain where both proteins are expressed. At P7, Rac3 staining is particularly marked in the deep cerebellar nuclei and in the pons, where it shows a discontinuous distribution around the neuronal cell bodies, in contrast with the diffuse staining of Rac1. Rac3 does not evidently co-localize with pre- and post-synaptic markers, nor with GFAP-positive astrocytes, but it clearly co-localizes with actin filaments, and with the terminal portions of calbindin-positive Purkinje cell axons in the deep cerebellar nuclei. Our data implicate Rac3 in neuronal differentiation, and support a specific role of this GTPase in actin-mediated remodelling of Purkinje cell neuritic terminals at time of synaptogenesis. [source] Moyamoya-disease-related ischemic stroke in the postpartum periodJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 5 2009Kei Miyakoshi Abstract Stroke during pregnancy or the puerperium is an extremely rare yet serious cause of perinatal morbidity and mortality. Moyamoya disease, a cerebrovascular occlusive pathology with a female predominance, may become symptomatic for the first time in association with pregnancy. A 36-year-old woman with postpartum pre-eclampsia suddenly developed hemiparesis in the left arm with dysarthria after the initiation of antihypertensive measures. Cranial magnetic resonance imaging and angiography revealed acute ischemic lesions in the right hemisphere along with the steno-occlusive lesions of bilateral terminal portions of the internal carotid artery, indicating Moyamoya disease. With anti-platelet medication, the patient recovered gradually and was diagnosed as having Moyamoya disease using conventional angiography 3 months postpartum. In this case, the fluctuations in blood pressure in association with pre-eclampsia appear to have exacerbated the clinical symptoms of Moyamoya disease. As such, Moyamoya disease should be considered as an underlying disease of ischemic stroke associated with pregnancy. [source] Immunohistochemical localization of Ih channel subunits, HCN1,4, in the rat brainTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 3 2004Takuya Notomi Abstract Hyperpolarization-activated cation currents (Ih) contribute to various physiological properties and functions in the brain, including neuronal pacemaker activity, setting of resting membrane potential, and dendritic integration of synaptic input. Four subunits of the Hyperpolarization-activated and Cyclic-Nucleotide-gated nonselective cation channels (HCN1,4), which generate Ih, have been cloned recently. To better understand the functional diversity of Ih in the brain, we examined precise immunohistochemical localization of four HCNs in the rat brain. Immunoreactivity for HCN1 showed predominantly cortical distribution, being intense in the neocortex, hippocampus, superior colliculus, and cerebellum, whereas those for HCN3 and HCN4 exhibited subcortical distribution mainly concentrated in the hypothalamus and thalamus, respectively. Immunoreactivity for HCN2 had a widespread distribution throughout the brain. Double immunofluorescence revealed colocalization of immunoreactivity for HCN1 and HCN2 in distal dendrites of pyramidal cells in the hippocampus and neocortex. At the electron microscopic level, immunogold particles for HCN1 and HCN2 had similar distribution patterns along plasma membrane of dendritic shafts in layer I of the neocortex and stratum lacunosum moleculare of the hippocampal CA1 area, suggesting that these subunits could form heteromeric channels. Our results further indicate that HCNs are localized not only in somato-dendritic compartments but also in axonal compartments of neurons. Immunoreactivity for HCNs often occurred in preterminal rather than terminal portions of axons and in specific populations of myelinated axons. We also found HCN2-immunopositive oligodendrocytes including perineuronal oligodendrocytes throughout the brain. These results support previous electrophysiological findings and further suggest unexpected roles of Ih channels in the brain. J. Comp. Neurol. 471:241,276, 2004. © 2004 Wiley-Liss, Inc. [source] | |||||||||||||