bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Catalytic Subunit of Dictyostelium cAMP‐Dependent Protein Kinase
Authors: Etchebehere Lilian C. , Van Bemmelen Miguel X. P. , Anjard Christophe , Traincard François , Assemat Karine , Reymond Christophe , Veron Michel 
Published: July 2004

The C subunit of Dictyostelium cAMP‐dependent protein kinase (PKA) is unusually large (73 kDa) due to the presence of 330 amino acids N‐terminal to the conserved catalytic core. The sequence following the core, including a C‐terminal‐Phe‐Xaa‐Xaa‐Phe‐COOH motif, is highly conserved. We have characterized the catalytic activity and stability of C subunits mutated in sequences outside the catalytic core and we have analyzed their ability to interact with the R subunit and with the heat‐stable protein‐kinase inhibitor PKI.Mutants carrying deletions in the N‐terminal domain displayed little difference in their kinetic properties and retained their capacity to be inhibited by R subunit and by PKI. In contrast, the mutation of one or both of the phenylalanine residues in the C‐terminal motif resulted in a decrease of catalytic activity and stability of the proteins. Inhibition by the R subunit or by PKI were however unaffected. Sequence‐comparison analysis of other protein kinases revealed that a‐Phe‐Xaa‐Xaa‐Phe‐motif is present in many Ser/Thr protein kinases, although its location at the very end of the polypeptide is a particular feature of the PKA family. We propose that the presence of this motif may serve to identify isoforms of protein kinases.
Linking Protein Kinase C to Cell‐Cycle Control
Authors: Livneh Etta , Fishman Daniel D. 
Published: July 2004

Protein kinase C (PKC) isoenzymes are involved in diverse cellular functions, including differentiation, growth control, tumor promotion, and cell death. In recent years, evidence has began to emerge suggesting a role for PKC in cell cycle control. A paper published recently, demonstrating a functional link between PKC and cell cycle control in yeast (Marini, N. J., Meldrum, E., Buehrer, B., Hubberstey, A. V., Stone, D. E., Traynor‐Kaplan, A. & Reed, S. I. (1996) EMBO J. 15, 3040–3052), strengthens this data. Thus, the existence of cell‐cycle‐regulated pathways involving PKC in both yeast and mammals indicate that PKC may be a conserved regulator of cell cycle events that links signal transduction pathways and the cell‐cycle machinery. In this paper, we will review current data on the cell cycle components that are targets for PKC regulation.PKC enzymes appear to operate as regulators of the cell cycle at two sites, during G1 progression and G2/M transition. In G1, the overall effect of PKC activation is inhibition of the cell cycle at mid to late G1. This cell cycle inhibition correlates with a blockage in the normal phosphorylation of the tumor suppressor retinoblastoma Rb protein, presumably through an indirect mechanism. The reduced activity of the cyclin‐dependent kinase, Cdk2, appears to be the major effect of PKC activation in various cell systems. This may also underlie the inhibition of Rb phosphorylation exhibited by PKC activation. Several mechanisms were described in different studies on the regulation of Cdk2 activity by PKC; reduced Cdk‐activating kinase activity, diminished expression of the Cdk2 partners cyclins E or A, and the increased expression of the cyclin‐dependent inhibitors, p21WAF1 and p27KIPI, which are capable of binding to cyclin/Cdk2 complexes.PKC enzymes were also shown to play a role in G2/M transition. Among the suggested mechanisms is suppression of Cdc2 activity. However, most of the published data strongly implicate PKC in lamin B phosphorylation and nuclear envelope disassembly.
Role of Leptin in Farm Animals: a Review
Authors: Máčajová M. , Lamošová D. , Zeman M. 
Published: July 2004

SummaryThe discovery of hormone leptin has led to better understanding of the energy balance control. In addition to its effects on food intake and energy expenditure, leptin has now been implicated as a mediator of diverse physiological functions. Recently, leptin has been cloned in several domestic species. The sequence similarity suggests a common function or mechanism of this peptide hormone across species. Leptin receptors are expressed in most of tissues, which is consistent with the multiplicity of leptin functions. The main goal of this review was to summarize knowledge about effect of leptin on physiology of farm animals. Experiments point to a stimulatory action of leptin on growth hormone (GH) secretion, normal growth and development of the brain. Surprisingly, leptin is synthesized at a high rate in placenta and may function as a growth factor for fetus, signalling the nutritional status from the mother to her offspring. Maturation of reproductive system can be stimulated by leptin administration. Morphological and hormonal changes, consistent with a major role of leptin in the reproductive system, have also been described, including the stimulation of the release of luteinizing hormone (LH), follicle‐stimulating hormone (FSH) and prolactin. Leptin has a substantial effect on food intake and feeding behaviour in animals. Administration of leptin reduces food intake. Its level decrease within hours after initiation of fasting. Leptin also serves as a mediator of the adaption to fasting, and this role may be the primary function for which was the molecule evolved.
A Comparison of Biopsy and Post‐mortem Findings in the Lungs of Healthy Cows
Authors: Sydler T. , Braun U. , Estermann U. , Pospischil A. 
Published: July 2004

SummaryLung biopsy in cattle for the diagnosis of lung diseases is rarely used or described. The clinical effects and the gross findings in lung and pleura after ultrasonic‐guided percutaneous lung biopsy in the upright animal of healthy cattle were reported previously (Braun et al., 1999). This report describes the yield of attained lung tissue and the local tissue reaction in 60 healthy adult cows slaughtered 24 h (50 animals) and 10 days (10 animals) after invasion. The yield of lung tissue in the biopsies was high (85.5%) in 90 histologically examined biopsy specimens and judged ‘good to excellent’. The local tissue reaction and the extent of haemorrhage in the lung parenchyma, both 24 h and 10 days after the biopsy, were minimal. In the latter group, the scar tissue had approximately the same dimensions as the tissue cylinders punched 10 days before. There were no local adhesions between the pleural surfaces. Previously published data concerning clinical reactions and complications, macroscopically examined local tissue bleeding and the histologically evaluated minimal local inflammatory reaction, following lung biopsy of cattle, indicate that this procedure is safe and satisfactory for sampling of accurate lung material. The results of this study concur and indicate that local complications in the animal were minimal to absent.
Relationships between Lactational Incidence of Displaced Abomasum and Milk Production Traits in German Holstein Cows
Authors: Hamann H. , Wolf V. , Scholz H. , Distl O. 
Published: July 2004

SummaryThe objective of this study was to analyse the heritabilitiy of the lactational incidence of displaced abomasum (DA) and the relationships of DA with milk production traits in German Holstein cows. Data were recorded between February 1999 and January 2000 in cooperation with five veterinary practitioners. Their veterinary practices were located in the northern part of Lower Saxony. The investigation included 160 dairy farms under the official milk‐recording scheme with 9315 cows. The lactational incidence of the left abomasal displacement amounted to 1.21%, and of the right abomasal displacement to 0.41%, respectively. The linear heritability estimates for the lactational incidences of left and right DA were h2 =0.05 ± 0.012 and h2 = 0.004 ± 0.005, respectively. Using the Dempster–Lerner‐transformation the corresponding heritabilities were h2 = 0.53 and 0.09, respectively. Milk losses for the lactation when DA was diagnosed were significant and reached 1016 kg milk, 41 kg fat, 36 kg protein and 0.07% protein. Fat content significantly increased by 0.18%. The analysis could not show significant differences between cows diagnosed with DA and cows not diagnosed with DA in the 305‐day milk production traits of the lactation preceding the diagnosis of DA. There was also no indication for an unequal distribution of breeding values for milk performance traits between cows with and without DA. The additive genetic correlations between 305‐day milk performance and left DA were low. The results indicated that cows with a high milk production and superior breeding values for milk performance were not exposed to an increased risk for DA.
Identification of a novel brain‐specific and reelin‐regulated gene that encodes a protein colocalized with synapsin
Authors: Kuvbachieva Anelia , Bestel Aude‐Marie , Tissir Fadel , Maloum Ismahane , Guimiot Fabien , Ramoz Nicolas , Bourgeois Francine , Moalic Jean‐Marie , Goffinet André M. , Simonneau Michel 
Published: July 2004

AbstractWe carried out a screening of genes that are differentially expressed in normal mice and reeler mutants and are characterized by abnormal neuronal migration and neurite deployment due to defective Reelin signalling. A novel gene, provisionally named C61, was overexpressed in Reelin‐deficient embryonic mouse brain RNA. C61 encodes a 3.7 kb mRNA that is brain specific and developmentally regulated, with predominant expression in differentiating neurons. The predicted protein is 664 amino acids long, and contains LAG1 and Ezrin/Radixin/Moesin‐Myosin‐Filament motifs, suggesting that it may function as an intracellular adaptor. From E14.5 to birth, C61 was highly expressed in all neuronal differentiation fields, with the highest signal in the telencephalic cortical plate and mitral cells in the olfactory bulb. When expressed as a GFP fusion protein in transfected non‐neuronal cells and primary neurons, this protein localizes, respectively, to the nuclear membrane or axonal outgrowths, indicating a function in axonal traffic or signalling.
Mechanism of GABAB receptor‐mediated inhibition of spontaneous GABA release onto cerebellar Purkinje cells
Authors: Harvey Victoria L. , Stephens Gary J. 
Published: July 2004

Abstractγ‐Aminobutyric acid (GABA)B receptor‐mediated modulation of spontaneous GABA release onto Purkinje cells was investigated in cerebellar slices from 3‐ to 5‐week‐old mice. The GABAB receptor agonists baclofen and CGP 44533 each reduced the frequency of miniature inhibitory postsynaptic currents (mIPSCs), with no significant effect on mIPSC amplitude; together, consistent with a presynaptic site of action. The GABAB receptor antagonist CGP 55845 blocked baclofen‐induced inhibition. The sulphydryl alkylating agent N‐ethylmaleimide occluded baclofen effects, implicating Gi/o subunits in mediating a GABAB G protein‐coupled receptor pathway. Baclofen‐induced inhibition persisted in the presence of Ba2+, a blocker of K+ channels, and Cd2+, a blocker of Ca2+ channel‐mediated GABA release. Application of nominally Ca2+‐free extracellular solutions reduced mIPSC frequency and amplitude; however, baclofen produced a significant inhibition in mIPSC frequency, further suggesting that this pathway was independent of Ca2+ influx. Spontaneous GABA release was increased by the adenylate cyclase activator, forskolin, and the phorbol ester, phorbol 12,13‐dibutyrate. However, baclofen‐induced inhibition was not significantly changed in either condition. Baclofen action was also not affected by the adenylate cyclase inhibitor SQ 22536 or the protein kinase C inhibitor chelerythrine chloride. Baclofen still reduced mIPSC frequency in the presence of the polyvalent cation ruthenium red, which acts as a secretagogue here; however, baclofen‐induced inhibition was reduced significantly. Furthermore, baclofen produced no clear inhibition during high‐frequency mIPSCs bursts induced by the potent secretagogue α‐Latrotoxin. Together, these results suggest that GABAB inhibition occurs downstream of Ca2+ influx and may be mediated, in part, by an inhibition of the vesicular release mechanism.
Evidence for differential modulation of conditioned aversion and fear‐conditioned analgesia by CB1 receptors
Authors: Finn D. P. , Beckett S. R. G. , Richardson D. , Kendall D. A. , Marsden C. A. , Chapman V. 
Published: July 2004

AbstractFear‐conditioned analgesia is an important survival response mediated by substrates controlling nociception and aversion. Cannabinoid1 (CB1) receptors play an important role in nociception and aversion. However, their role in fear‐conditioned analgesia has not been investigated. This study investigated the effects of systemic administration of the CB1 receptor antagonist, SR141716A (1 mg/kg, ip), on fear‐conditioned analgesia and conditioned aversion in rats. Twenty‐four hours after receiving footshock, rats exhibited reduced formalin‐evoked nociceptive behaviour, increased freezing and increased defecation when tested in the footshock apparatus, compared with non‐footshocked formalin‐injected rats. SR141716A attenuated fear‐conditioned analgesia, freezing and defecation. Importantly, SR141716A had no effect on formalin‐evoked nociceptive behaviour over an equivalent time period in rats not receiving footshock. SR141716A had no effect on contextually induced freezing during the first half of the test trial in rats receiving intra‐plantar injection of saline. Administration of SR1417176A did, however, attenuate short‐term extinction of contextually induced freezing and ultrasound emission in rats receiving intra‐plantar saline, compared with vehicle‐treated saline controls. These data suggest an important role for the CB1 receptor in mediating fear‐conditioned analgesia and provide evidence for differential modulation of conditioned aversive behaviour by CB1 receptors during tonic, persistent pain.
Subcortical visual system of the African mole‐ratCryptomys anselli: to see or not to see?
Authors: Němec Pavel , Burda Hynek , Peichl Leo 
Published: July 2004

AbstractWe studied the retinal projections, the distribution of cytochrome oxidase activity and the cyto‐ and myeloarchitecture of the subcortical visual system in the subterranean Ansell's mole‐ratCryptomys anselli. The optic nerve contained 1500 myelinated and a similar number of unmyelinated fibres. The retina projected to all the visual structures described in surface‐dwelling sighted rodents. The suprachiasmatic nucleus was large and received bilateral retinal input. All other visual nuclei were reduced in size, were cytoarchitecturally poorly developed and received almost exclusively contralateral retinal projections. The dorsal and ventral lateral geniculate nuclei were moderately reduced and heavily innervated. The intergeniculate leaflet could be identified between these two nuclei. Pretectal nuclei were also relatively well‐developed. The nucleus of the optic tract, the olivary pretectal nucleus, and the anterior and posterior pretectal nuclei were innervated by the retina. By contrast, the superficial, retinorecipient layers of the superior colliculus showed extreme reduction. The strata zonale, griseum superficiale and opticum were collapsed to a single layer 40 µm thick. The accessory optic system was vestigial. These findings indicate that the functional subsystems involved in photoperiod perception, form and brightness discrimination, and movement analysis are anatomically rather well developed, whereas those involved in coordination of visuomotor reflexes are severely reduced. Thus, the visual system ofC. anselliis much better developed than that of the blind mole‐ratSpalax ehrenbergi.We suggest thatCryptomys ansellihas retained basic visual capabilities.
Neurotrophins induce short‐term and long‐term changes of cortical neurotrophin expression
Authors: Patz Silke , Wahle Petra 
Published: July 2004

AbstractNeuronal activity, hormones, transmitters, physical exercise and enrichment influence cortical neurotrophin expression. Neurotrophins then elicit structural and physiological changes, and regulate gene expression. This prompted the hypothesis that neurotrophins themselves are involved in regulating neurotrophin expression. Here we investigated the mRNA expression level of brain‐derived neurotrophic factor (BDNF), neurotrophin‐4 (NT‐4), NT‐3 and nerve growth factor (NGF) as well as the tyrosine receptor kinases TrkB and TrkC receptor in response to BDNF, NT‐4, NT‐3 and NGF pulses in organotypic cortex cultures. Single neurotrophin pulses evoked a dramatic up‐ or down‐regulation of some, but not all four, neurotrophin mRNAs, even within 3–24 h, indicating an immediate impact on neurotrophin transcription. Most strikingly, neurotrophin pulses during the first 10 days in vitro (DIV) potentiated the expression of some neurotrophin mRNAs at 20 DIV, suggesting that early trophic factor experience influences the expression levels seen later in development. The NT‐3 mRNA expression, for example, was consistently promoted by NGF and BDNF, suggesting that these two factors help to maintain the low level of NT‐3 found in adult cortex. Rapid bidirectional changes characterized the NT‐4 mRNA expression. A single pulse of NT‐4 transiently increased NT‐4 mRNA, whereas a BDNF pulse transiently reduced NT‐4 mRNA. Surprisingly, NGF strongly potentiated BDNF mRNA and in particular NT‐4 mRNA. By contrast, TrkB mRNA remained constant at ages or time points at which other mRNAs amplified from the very same cDNA libraries revealed dramatic increases or decreases. Our study suggests the existence of a complex regulatory neurotrophin network controlling the expression of other neurotrophins.
Voltage‐gated K+ current: a marker for apoptosis in differentiating neuronal progenitor cells?
Authors: Hribar Marusa , Bloc Alain , Medilanski Jeana , Nüsch Lars , Eder‐Colli Lorenza 
Published: July 2004

AbstractWe investigated apoptosis during early stages of in vitro differentiation of neuronal precursors generated by embryonic day 14 (E14) mouse striata stem cells. Differentiation was in conditions of suboptimal growth factor supply. Apoptosis reached 10–15% of cells and affected proliferating as well as postmitotic cells, including TUJ1‐positive cells. Inhibition of apoptosis led to an increased proportion of TUJ1‐positive cells generated by stem cells. K+ current was reported to be related to apoptosis. Outward K+ currents were present in differentiating neuronal precursors that were consistent with delayed rectifier and transient A‐type currents. The amplitude of the delayed rectifier current varied during the first 4 days of stem cell differentiation. Current amplitude was greatly increased in the presence of staurosporine but reduced at elevated extracellular K+ concentration. In addition, the amplitude of the current was significantly diminished by inhibiting several caspases, but not caspase 8. In Bax knock‐out transgenic neuronal precurors, K+ current was not decreased after the first day but at later stages of cell differentiation. At this early stage, apoptosis of proliferating cells and of TUJ1‐positive cells was not reduced by the absence of Bax, but was by caspase 9 inhibition. Thus, activation of a delayed rectifier K+ current in differentiating stem cells is related to apoptosis. Recordings of this current revealed that apoptosis at early stages of neuronal differentiation occurred in two phases that did not exhibit similar dependence on the proapoptotic protein Bax and that probably used different pathways.
Brain‐derived neurotrophic factor is expressed in a gradient in the superior colliculus during development of the retinocollicular projection
Authors: Marotte L. R. , Vidovic M. , Wheeler E. , Jhaveri S. 
Published: July 2004

AbstractTheoretical models of topographic map formation have postulated a gradient of attractant in addition to a gradient of repulsion in the target. In species where many axons grow past their correct positions initially, it has also been argued that a parallel gradient of attractant or branching signal is required to ensure collateral formation at the correct position (O'Leary et al., 1999). Brain‐derived neurotrophic factor (BDNF) is a known attractant and promotes branching of retinal axons. We have examined its distribution in the superior colliculus and that of its receptor, trkB, in the retina, using immunohistochemistry and in situ hybridization, respectively, during the development of the topographic retinocollicular projection in the wallaby, a marsupial mammal. The number of glial endfeet expressing BDNF at the surface of the colliculus was found to be in a high caudal‐to‐low rostral gradient during the time when the retinocollicular projection was developing. When the projection was mature the rostrocaudal gradient had disappeared and the number of detectable endfeet expressing BDNF was very low. Messenger RNA for TrkB was expressed in the retinal ganglion cell layer throughout the time when the retinocollicular projection was developing, with no difference in expression across the nasotemporal axis of the retina. The low rostral to high caudal distribution of BDNF in glial endfeet supports the idea that it is providing a parallel gradient of attractant or branching signal in the colliculus.
Reward expectation, orientation of attention and locus coeruleus‐medial frontal cortex interplay during learning
Authors: Bouret Sebastien , Sara Susan J. 
Published: July 2004

AbstractRegulation of attention and promotion of behavioural flexibility are functions attributed to both the noradrenergic nucleus locus coeruleus (LC) and the prefrontal cortex (PFC). The PFC receives a large innervation from LC and small changes in catecholaminergic activity in PFC profoundly affect cognitive function. It is crucial to the understanding of learning‐related plasticity, that the cognitive context driving LC neurons be determined and the relation to activity in PFC be elucidated. To this end simultaneous recordings were made from LC and prelimbic cortex (PL) during an odour‐reward association task in the rat. Neuronal activity related to orientation of attention, reward predictability, reward itself, and changes in stimulus reinforcement contingencies, was measured. All LC neurons and a significant proportion of PL neurons were engaged during several aspects of a Go/NoGo task, especially after the signal for trial onset and CS+ presentation. LC activation was, however, more tightly aligned to the behavioural response than to the CS+ 22% of PL neurons were activated during the response‐reward delay. This suggests that the activity of both these structures is related to reward anticipation. Finally, LC neurons exhibited rapid plasticity when the reward‐contingency was modified. Within‐trial response latencies were always shorter in LC than in PL and between‐trial response adaptation in LC preceded that in PL by many trials. Identifying such temporal relationships is an essential step toward understanding how neuromodulatory inputs to forebrain networks might promote or permit experience‐dependent plasticity in behavioural situations.