bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of Sin recombinase by accessory proteins
Authors: Rowland Sally J. , Boocock Martin R. , Stark W. Marshall
Published: March 2005

Sin recombinase fromStaphylococcus aureusacts selectively on directly repeatedresHsites, assembling an intertwined synapse in which exactly three supercoils are trapped between the points of strand exchange. Resolution requires the two Sin binding sites inresH(site I, where strand exchange occurs, and site II) and a non‐specific DNA‐bending protein (e.g. Hbsu). We show that a single amino acid substitution in Sin (I100T) is sufficient to relax the normal requirements for site II and Hbsu. Using this hyperactive protein, and the variant recombination siteresHAT, we investigate the roles of site II and Hbsu in synapsis and strand exchange. We conclude that Sin bound at site II, and Hbsu, act together to control site I alignment and the topology of the synapse, and to stimulate strand exchange.
Protein kinase C modulates light responses in Neurospora by regulating the blue light photoreceptor WC‐1
Authors: Franchi Lisa , Fulci Valerio , Macino Giuseppe
Published: March 2005

The Neurospora protein kinase C (NPKC) is a regulator of light responsive genes. We have studied the function of NPKC in light response by investigating its biochemical and functional interaction with the blue light photoreceptor white‐collar 1 (WC‐1), showing that activation of NPKC leads to a significant decrease in WC‐1 protein levels. Furthermore, we show that WC‐1 and NPKC interact in a light‐regulated manner in vivo, and that protein kinase C (PKC) phosphorylates WC‐1 in vitro. We designed dominant negative and constitutively active forms of PKC which are able to induce either a large increase of WC‐1 protein level or a strong reduction respectively. Moreover, these changes in PKC activity result in an altered light response. As WC‐1 is a key component of Neurospora circadian clock and regulates the clock oscillator component FRQ we investigated the effect of NPKC‐mutated forms on FRQ levels. We show that changes in PKC activity affect FRQ levels and the robustness of the circadian clock. Together these data identify NPKC as a novel component of the Neurospora light signal transduction pathway that modulates the circadian clock.
Blue light negatively regulates the sexual filamentation via the Cwc1 and Cwc2 proteins in Cryptococcus neoformans
Authors: Lu Ying‐Ku , Sun Kai‐Hui , Shen Wei‐Chiang
Published: March 2005

Cryptococcus neoformans is a heterothallic basidiomycetous yeast that primarily infects immunocompromised individuals. Dikaryotic hyphae resulting from the fusion of the MATa and MATα mating type strains represent the filamentous stage in the sexual life cycle of C. neoformans. In this study we demonstrate that the production of dikaryotic filaments is inhibited by blue light. To study blue light photoresponse in C. neoformans, we have identified and characterized two genes, CWC1 and CWC2, which are homologous to Neurospora crassa wc‐1 and wc‐2 genes. Conserved domain analyses indicate that the functions of Cwc1 and Cwc2 proteins may be evolutionally conserved. To dissect their roles in the light response, the CWC1 gene deletion mutants are created in both mating type strains. Mating filamentation in the bilateral cross of cwc1 MATa and MATα strains is not sensitive to light. The results indicate that Cwc1 may be an essential regulator of light responses in C. neoformans. Furthermore, overexpression of the CWC1 or CWC2 gene requires light activation to inhibit sexual filamentation, suggesting both genes may function together in the early step of blue light signalling. Taken together, our findings illustrate blue light negatively regulates the sexual filamentation via the Cwc1 and Cwc2 proteins in C. neoformans.
Respiration metabolism of Group B Streptococcus is activated by environmental haem and quinone and contributes to virulence
Authors: Yamamoto Yuji , Poyart Claire , Trieu‐Cuot Patrick , Lamberet Gilles , Gruss Alexandra , Gaudu Philippe
Published: March 2005

Group B Streptococcus (GBS) is a common constituent of the vaginal microflora, but its transmission to newborns can cause life‐threatening sepsis, pneumonia and meningitis. Energy metabolism of this opportunist pathogen has been deduced to be strictly fermentative. We discovered that GBS undergoes respiration metabolism if its environment supplies two essential respiratory components: quinone and haem. Respiration metabolism led to significant changes in growth characteristics, including a doubling of biomass and an altered metabolite profile under the tested conditions. The GBS respiratory chain is inactivated by: (i) withdrawing haem and/or quinone, (ii) treating cultures with a respiration inhibitor or (iii) inactivating the cydA gene product, a subunit of cytochrome bd quinol oxidase, in all cases resulting in exclusively fermentative growth. cydA inactivation reduced GBS growth in human blood and strongly attenuated virulence in a neonatal rat sepsis model, suggesting that the animal host may supply the components that activate GBS respiration. These results suggest a role of respiration metabolism in GBS dissemination. Our findings show that environmental factors can increase the flexibility of GBS metabolism by activating a newly identified respiration chain. The need for two environmental factors may explain why GBS respiration metabolism was not found in previous studies.
Defining the role of PfCRT in Plasmodium falciparum chloroquine resistance
Authors: Bray Patrick G. , Martin Rowena E. , Tilley Leann , Ward Stephen A. , Kirk Kiaran , Fidock David A.
Published: March 2005

Recent studies have highlighted the importance of a parasite protein referred to as the chloroquine resistance transporter (PfCRT) in the molecular basis of Plasmodium falciparum resistance to the quinoline antimalarials. PfCRT, an integral membrane protein with 10 predicted transmembrane domains, is a member of the drug/metabolite transporter superfamily and is located on the membrane of the intra‐erythrocytic parasite's digestive vacuole. Specific polymorphisms in PfCRT are tightly correlated with chloroquine resistance. Transfection studies have now proven that pfcrt mutations confer verapamil‐reversible chloroquine resistance in vitro and reveal their important role in resistance to quinine. Available evidence is consistent with the view that PfCRT functions as a transporter directly mediating the efflux of chloroquine from the digestive vacuole.
The mutation G145S in PrfA, a key virulence regulator of Listeria monocytogenes, increases DNA‐binding affinity by stabilizing the HTH motif
Authors: Eiting Marina , Hagelüken Gregor , Schubert Wolf‐Dieter , Heinz Dirk W.
Published: March 2005

Listeria monocytogenes, a Gram‐positive, facultative intracellular human pathogen, causes systemic infections with high mortality rate. The majority of the known pathogenicity factors of L. monocytogenes is regulated by a single transcription factor, PrfA. Hyperhaemolytic laboratory strains of L. monocytogenes express the constitutively active mutant PrfAG145S inducing virulence gene overexpression independent of environmental conditions. PrfA belongs to the Crp/Fnr family of transcription factors generally activated by a small effector, such as cAMP or O2. We present the crystal structures of wild‐type PrfA, the first Gram‐positive member of the Crp/Fnr family, and of the constitutively active mutant PrfAG145S. Cap (Crp) has previously been described exclusively in the cAMP‐induced (DNA‐free and ‐bound) conformation. By contrast, the PrfA structures present views both of the non‐induced state and of the mutationally activated form. The low DNA‐binding affinity of wild‐type PrfA is supported both structurally (partly disordered helix–turn–helix motif, overall geometry of the HTH α‐helices deviates from Cap) and by surface plasmon resonance analyses (KD = 0.9 µM). In PrfAG145S the HTH motifs dramatically rearrange to adopt a conformation comparable to cAMP‐induced Cap and hence favourable for DNA binding, supported by a DNA‐binding affinity of 50 nM. Finally, the hypothesis that wild‐type PrfA, like other Crp/Fnr family members, may require an as yet unidentified cofactor for activation is supported by the presence of a distinct tunnel in PrfA, located at the interface of the β‐barrel and the DNA‐binding domain.
Comparison of assays for determination of peptide content for lyophilized thymalfasin*
Authors: Vemuri S.
Published: March 2005

Abstract:  Precise determination of the peptide content in drug substance samples depends highly upon the particular peptide compound and methodology used. Four independent methods were evaluated and compared to determine which would produce the best experimental precision for analysis of thymalfasin (thymosin α‐1). Four different methods were evaluated including elemental analysis (CHN), quantitative amino acid analysis (AAA), high‐performance liquid chromatography (HPLC), and Kjeldahl. This study demonstrates that the AAA method is highly variable in one laboratory while quite precise in another laboratory. Similarly, HPLC results depended on the laboratory conducting the study with more precise values obtained under cGMP. On the contrary, the CHN method yielded highly precise [i.e. <2% coefficient of variation (CV)] values. As precise knowledge of protein content is fundamental for the compounding of final pharmaceutical product of a specific potency, the CHN analysis is recommended for peptide content determination of the drug substance thymalfasin.
One pot conjugation of the polypeptides directed by phosphorus oxychloride
Authors: Zhou N. , Liu Y. , Zhou G. J. , Zhao Y. F.
Published: March 2005

Abstract:  A series of homopeptides and their conjugates were synthesized in one pot reaction in the presence of phosphorus oxychloride and the conjugate yield was structurally dependent. Menthol and benzylamine conjugated to the homopeptides quantitatively. Homopeptides when treated with diisopropyloxyphosphite (DIPPH) and NaClO yield the corresponding N‐phosphoryl peptides. Electrospray ionization‐mass spectrometry (ESI‐MS)/MS was used to study the structure of peptide conjugates. This paper reports a simple method to synthesize the homopeptides and their conjugate derivatives and the fact that phosphoryl peptides could also be obtained by one pot reaction.
Biosynthesis and purification of a hydrophobic peptide from transmembrane domains of G‐protein‐coupled CB2 receptor
Authors: Zheng H. , Zhao J. , Wang S. , Lin C.‐M. , Chen T. , Jones D.H. , Ma C. , Opella S. , Xie X.‐Q.
Published: March 2005

Abstract:  A major challenge for the structural study of the seven‐transmembrane G‐protein‐coupled receptors is to obtain a sufficient amount of purified protein at the milligram level, which is required for either nuclear magnetic resonance (NMR) spectroscopy or X‐ray crystallography. In order to develop a high‐yield and cost‐effective method, and also to obtain preliminary structural information for the computer modeling of the three‐dimensional receptor structural model, a highly hydrophobic peptide from human cannabinoid subtype 2 receptor CB265−101, was chosen to develop high‐yield membrane protein expression and purification methods. The peptide included the second transmembrane helix with the associated loop regions of the CB2 receptor. It was over‐expressed in Escherichia coli, with a modified TrpΔ LE1413 (TrpLE) leading fusion sequence and a nine‐histidine tag, and was then separated and purified from the tag in a preparative scale. An experimental protocol for the chemical cleavage of membrane protein fragment was developed using cyanogen bromide to remove the TrpLE tag from the hydrophobic fusion protein. In addition, protein uniformly labeled with isotopic 15N was obtained by expression in 15N‐enriched minimum media. The developed and optimized preparation scheme of expression, cleavage, and purification provided a sufficient amount of peptide for NMR structure analysis and other biophysical studies that will be reported elsewhere. The process of fusion protein cleavage following purification was monitored by high‐performance liquid chromatography (HPLC) and mass spectrometry (MS), and the final sample was validated by MS and circular dichroism experiments.
The Effect of Different Timing of Top Dressing of Nitrogen Application under Low Light Intensity on the Yield of Rice (Oryza sativa L.)
Authors: Samarajeewa K. B. D. P. , Kojima N. , Sakagami J.‐I. , Chandanie W. A.
Published: March 2005

Three levels of shade (0, 45 and 70 %) on rice was studied by changing the time of nitrogen top dressing application. The shade was given for the respective plots from heading up to harvesting and the top dressing was applied 20 days (standard) and 5 days (late) before heading. Significant yield reduction was not observed under the given conditions but ripening percentage and thousand‐grain weight was significantly affected. Ripening rate was found as the key factor that determined the rice yield under low light intensities. The adverse effects of shade on the yield and yield components were not able to significantly minimize by the change of the timing of application of nitrogen top dressing.
Alexithymia and dissociative tendencies in an adolescent sample from Eastern Turkey
Authors: SAYAR KEMAL , KOSE SAMET , GRABE HANS J. , TOPBAS MURAT
Published: March 2005

Abstract  Alexithymia and dissociative reactions are two strategies that have been put forward as coping mechanisms to alleviate painful emotions. Adult studies reveal an association between alexithymia and dissociation. In line with the coping hypothesis, it was predicted that the relationship between alexithymia and dissociative tendencies would be partly mediated by current levels of stress and past traumatic experiences. Dissociation may also be related to enhanced fantasizing, although alexithymia has traditionally been associated with an incapacity to fantasize. This relationship has not been studied well in adolescents. In the present study, 173 randomly selected high school students from Eastern Turkey were assessed with the Adolescent Dissociative Experiences Scale, the Beck Depression and Anxiety inventories, the Rosenberg Self‐esteem Scale and the Toronto Alexithymia Scale. Correlation analyses followed by stepwise regression analyses were performed. ‘Difficulty identifying feelings’ subscale of Toronto Alexithymia Scale, anxiety level and the history of physical abuse emerged as predictors of dissociative tendencies. It seems that in this group, dissociation is associated with anxiety and with difficulty in identifying feelings. Physical abuse also contributes to dissociation. The adolescent who is alexithymic may be more prone to dissociation when compared to their non‐alexithymic peers. Helping alexithymic adolescents describe their body experiences may decrease their tendency to dissociation by increasing their ability to verbally identify their stressors.
Association between the 5‐HT6 receptor C267T polymorphism and response to antidepressant treatment in major depressive disorder
Authors: LEE SEUNG‐HWAN , LEE KANG‐JOON , LEE HEON‐JEONG , HAM BYUNG‐JOO , RYU SEUNG‐HO , LEE MIN‐SOO
Published: March 2005

Abstract  The purpose of the present study was to determine if a 5‐HT6 receptor polymorphism is associated with antidepressant treatment response in major depressive disorder (MDD). Ninety‐one patients with MDD, compared with 127 normal control subjects, were evaluated after an 8‐week treatment period. An association analysis revealed no differences in genotype and allele distribution between patients with MDD and normal control subjects. However, there were significant differences in the treatment response in some Hamilton Depression Rating Scale (HAM‐D) scores (sleep, activity, somatic anxiety, and total) between genotypes. Moreover, the heterozygote group (CT genotype) had significantly better treatment response than the homozygote group (CC + TT genotypes), especially in the somatic‐anxiety subcategory and the total score of HAM‐D. These findings imply that a 5‐HT6 receptor polymorphism (C267T) is associated with treatment response in MDD.
Substance abuse, conduct disorder and crime: Assessment in a juvenile detention house in Istanbul, Turkey
Authors: COPUR MAZLUM , TURKCAN AHMET , ERDOGMUS MERAL
Published: March 2005

Abstract  The purpose of the present study was to determine the rate of substance abuse in the juvenile detention house and to determine the relationship between crime and substance abuse and conduct disorder. Two hundred and thirty cases in the biggest juvenile detention house in Istanbul, Turkey were assessed according to Diagnostic and Statistical Manual of Mental Disorders (4th edn; DSM‐IV) criteria. Law files and data of crime were examined. A total of 80 out of 230 juvenile detainees (34.8%) were found to have substance abuse excluding nicotine and alcohol. The substances abused in preferential order were cannabis (72.5%), volatile substances (21.3% bally and 3.7% thinner; 25%) and sedative hypnotic drugs and biperidents (2.5%). The rate of conduct disorder was 46.3% in substance abusers and 25.3% in the others (odds ratio: 2.536). The rate of substance abuse was 48.5% in the juveniles who had committed multiple crimes and 14.1% in the others (odds ratio: 5.735). The study shows that conduct disorder was very high in juvenile detainees. Conduct disorder was higher in substance‐abusing than in non‐abusing juvenile detainees. Substance‐abusing juvenile detainees were found to have a higher detention rate than non‐abusing juvenile detainees. There was a close relation between conduct disorder and substance abuse and multiple crimes. In the light of these results, diagnosis and treatment for conduct disorder in juvenile detainees are of great importance.
Factors associated with the development of panic attack and panic disorder: Survey in the Japanese population
Authors: KAIYA HISANOBU , UMEKAGE TADASHI , HARADA SEI‐ICHI , OKAZAKI YUJI , SASAKI TSUKASA
Published: March 2005

Abstract  Environmental factors, in addition to genetic factors, may be related to the development of panic attack (PA) and panic disorder (PD). Previous studies suggested that there may be seasonal variation in the onset of PA/PD and possibly a higher prevalence of PA/PD in colder areas. Also observed were lactate‐induced PA and elevated serum cholesterol in PD patients. These suggest that living environment and lifestyle, such as weather conditions, preference of food and physical exercise, might play a role in the occurrence of PA and PD. The present study explored the association of such candidate factors with the development of PA and PD in 4000 Japanese subjects, using a questionnaire. The subjects were recruited from the general population of Japan, using stratified random sampling. Logistic regression with stepwise selection of variables was employed for statistical analysis. Variables including ‘dislike of physical exercise’, mostly in female subjects, and ‘living in areas with longer winter’, in male subjects, were suggested for associations with PA and PD among the candidate factors. The result is preliminary but indicates that lifestyle such as like/dislike of physical exercise and environmental factors including weather conditions could play a partial role in the development of PA and PD. Further investigations are required before firm conclusions can be reached.
Antipsychotics and dopamine transporter gene polymorphisms in delirium patients
Authors: KIM JEE‐YEON , JUNG IN‐KWA , HAN CHANGSU , CHO SOOK‐HAENG , KIM LEEN , KIM SEUNG‐HYUN , LEE BUN‐HEE , LEE HEON‐JEONG , KIM YONG‐KU
Published: March 2005

Abstract  The main objective of the present study was to determine the relationship between treatment responses of delirium and genetic polymorphisms in the dopamine transporter. The optimal dosages of haloperidol and risperidone in the treatment of delirium were also investigated. Either haloperidol or risperidone was administered to delirium patients, and delirium symptoms were measured daily until remission. Variable number of tandem repeat (VNTR) polymorphisms of the dopamine transporter were determined using the polymerase chain reaction. Among 42 subjects, symptoms of delirium appeared a mean of 9.68 days after hospitalization. A majority of the subjects (83.3%) had the type 10/10 polymorphism. Dosages of haloperidol and risperidone at the day of recovery were 1.67 mg/day (SD = 1.32; range 0.5–2.5 mg/day) and 1.19 mg/day (SD = 1.14; range 0.5–5.0 mg/day), respectively. The mean drug response time was 8.5 days in the haloperidol group and 4.8 days in the risperidone group (no significant difference). The response rates at the 3rd and 7th days after medication did not differ with either the drug group or the dopamine transporter polymorphism. Relatively low doses of risperidone and haloperidol exhibited similar efficacies, and dopamine transporter polymorphisms do not appear to play a major role in the action of antipsychotics on delirium.
Actigraphic assessment of sleep in young adults with Asperger syndrome
Authors: TANI PEKKA , LINDBERG NINA , WENDT TAINA NIEMINEN‐VON , VON WENDT LENNART , ALANKO LAURI , APPELBERG BJÖRN , PORKKA‐HEISKANEN TARJA
Published: March 2005

Abstract  A high prevalence of subjective insomnia in adults with Asperger syndrome has been reported. In the present study the sleep quality of these patients was studied using wrist actigraphy. Nineteen adults with Asperger syndrome and frequent feelings of insomnia were compared with 10 controls devoid of neuropsychiatric disorders and subjective sleep problems during six consecutive nights. The patients had similar actigraphic sleep profile to the controls. The subjective low sleep quality in patients was not reflected in actigraphic assessment of sleep. This finding suggests that pervasive anxiety inherent in persons with Asperger syndrome predisposes them to insomnia complaints.
Wasp community responses to habitat complexity in Sydney sandstone forests
Authors: LASSAU SCOTT A. , HOCHULI DIETER F.
Published: March 2005

Abstract Habitat structure and complexity affect the diversity and composition of fauna in a number of systems. We investigated patterns in wasp species richness, abundance and composition and also their associations with habitat complexity in Sydney sandstone forests, Australia. Pitfall and flight‐intercept traps collected dissimilar wasp assemblages. High complexity habitats supported greater abundance and species richness and a dissimilar composition of pitfall‐trapped wasps to low complexity habitats. Soil moisture, tree canopy cover, ground herb cover and shrub canopy cover all had significant positive associations with the species richness of pitfall‐trapped wasps. Although the five most abundant families of wasps we trapped are endoparasitoids of other arthropods, they showed a variety of preferences for habitat variables. The mechanisms driving associations between habitat complexity and patterns in wasp communities may also provide a basis for understanding factors influencing the regulation of arthropod assemblages by wasps in agricultural and natural landscapes.
Scales of dispersal among hosts in a herbivorous marine amphipod
Authors: POORE ALISTAIR G. B.
Published: March 2005

Abstract The spatial arrangement of plants may constrain the expression of herbivore preferences due to interaction between the scales of herbivore mobility and vegetation structure. I tested the hypothesis that the presence of the herbivorous marine amphipodPeramphithoe parmerong(Ampithoidae) on a low‐preference, poor‐quality host (the brown algaPadina crassa) was due to limited dispersal and the clumped nature of algal distributions. In contrast to limited dispersal in laboratory assays, amphipods rapidly colonized vacant algae in the field with natural densities being achieved within 1 day. These high rates of colonization did not decline with increasing distance from existing algal beds over the spatial scales separatingPa. crassafrom the higher‐quality host algae (Sargassumspp.). Thus, the spatial arrangement of host algae did not interact with herbivore mobility to constrain host choices.
Different responsiveness of striatonigral and striatopallidal neurons to L‐DOPA after a subchronic intermittent L‐DOPA treatment
Authors: Carta A. R. , Tronci E. , Pinna A. , Morelli M.
Published: March 2005

Early gene induction by L‐DOPA in the striatum of dopamine denervated rats represents a useful way to study long‐term modifications produced by this drug. The effects of acute and subchronic L‐DOPA administration on zif‐268 mRNA expression were compared in 6‐hydroxydopamine‐lesioned rats. Rats received a subchronic intermittent L‐DOPA (6 mg/kg) treatment, which produces behavioural sensitization, a correlate of dyskinetic movements. Three days after interruption of subchronic treatment, zif‐268 mRNA was evaluated after an L‐DOPA challenge. Zif‐268 mRNA levels increased in the lesioned dorsolateral striatum after either acute or subchronic L‐DOPA administration. Double labelling of striatal cells with zif‐268 and enkephalin or dynorphin mRNA probes was performed to assess neuronal activation in the indirect and direct output pathway. Single acute L‐DOPA significantly increased zif‐268 in all striatal neurons reflecting a hyperresponsiveness of dopamine‐depleted striatum. After subchronic L‐DOPA, zif‐268 mRNA labelling was still increased in the striatonigral pathway, limited to dynorphin+ neurons, whereas in all other neurons it was similar to the control value. Results suggest that striatal neurons responding to acute L‐DOPA differ from those responding to subchronic L‐DOPA. L‐DOPA‐induced behavioural sensitization was associated to a down‐regulation in the responsiveness of striatopallidal and striatonigral dynorphin– neurons, whereas in striatonigral neurons containing dynorphin a hyperresponsiveness to L‐DOPA was observed. High levels of zif‐268, together with a persistent hyperresponsiveness of striatonigral dymorphinergic neurons and hyporesponsiveness of striatopallidal neurons, by creating an unbalanced state of striatal efferent neurons, may be implicated in dyskinetic movements observed in Parkinson's disease (PD).
Defective control and adaptation of reflex eye movements in mutant mice deficient in either the glutamate receptor δ2 subunit or Purkinje cells
Authors: Katoh Akira , Yoshida Takashi , Himeshima Yufuko , Mishina Masayoshi , Hirano Tomoo
Published: March 2005

The ionotropic glutamate receptor δ2 subunit (GluRδ2) is selectively expressed in cerebellar Purkinje cells and is implicated in long‐term depression, synaptic formation and elimination. To study the effect of GluRδ2 deficiency on motor control, we measured the vestibulo‐ocular reflex (VOR) and optokinetic response (OKR) induced by sinusoidal rotation of the animal and/or the surrounding screen in two GluRδ2 mutant mice: a GluRδ2 knockout mouse (δ2–/–) and a lurcher mouse with a point mutation in the GluRδ2 gene resulting in loss of all Purkinje cells. δ2–/– showed significantly higher VOR gain in the dark (VORD) than in the wild‐type. In δ2–/–, the VOR gain in light was lower than that in the dark. The phase of OKR lagged more in δ2–/– than in lurcher and wild‐type mice. Both mutant mice failed to change the VORD or OKR gain adaptively in response to sustained vestibular and/or visual stimulation. Basal properties of VOR and OKR changed little by lesion of the flocculus, but they changed substantially by lesion of the inferior olivary nuclei (IO). The abnormal VOR gain and OKR phase delay were clearly reduced in δ2–/– by the latter lesion. Our results indicate that failures in the GluRδ2‐dependent synaptic regulation affect motor performance more severely than loss of cerebellar cortical outputs. This study suggests that the anomalies in δ2–/– are dependent on inputs from IO and that GluRδ2 deficiency changed properties of not only the cerebellar cortex but also the brainstem neuronal pathways controlling reflex eye movements during development.
Differential regulation of type I and type II interleukin‐1 receptors in focal brain inflammation
Authors: Docagne Fabian , Campbell Sandra J. , Bristow Adrian F. , Poole Stephen , Vigues Stephan , Guaza Carmen , Perry V. Hugh , Anthony Daniel C.
Published: March 2005

Most pathologies of the brain have an inflammatory component, associated with the release of cytokines such as interleukin‐1β (IL‐1β) from resident and infiltrating cells. The IL‐1 type I receptor (IL‐1RI) initiates a signalling cascade but the type II receptor (IL‐1RII) acts as a decoy receptor. Here we have investigated the expression of IL‐1β, IL‐1RI and IL‐1RII in distinct inflammatory lesions in the rat brain. IL‐1β was injected into the brain to generate an inflammatory lesion in the absence of neuronal cell death whereas neuronal death was specifically induced by the microinjection of N‐methyl‐d‐aspartate (NMDA). Using TaqMan RT‐PCR and ELISA, we observed elevated de novo IL‐1β synthesis 2 h after the intracerebral microinjection of IL‐1β; this de novo IL‐1β remained elevated 24 h later. There was a concomitant increase in IL‐1RI mRNA but a much greater increase in IL‐1RII mRNA. Immunostaining revealed that IL‐1RII was expressed on brain endothelial cells and on infiltrating neutrophils. In contrast, although IL‐1β and IL‐1RI were elevated to similar levels in response to NMDA challenge, the response was delayed and IL‐1RII mRNA expression was unchanged. The lesion‐specific expression of IL‐1 receptors suggests that the receptors are differentially regulated in a manner not directly related to the endogenous level of IL‐1 in the CNS.
Intracerebral study of gamma rhythm reactivity in the sensorimotor cortex
Authors: Szurhaj William , Bourriez Jean‐Louis , Kahane Philippe , Chauvel Patrick , Mauguière François , Derambure Philippe
Published: March 2005

The generators and functional correlates of gamma oscillations within the sensorimotor cortex remain unclear. With the goal of locating the oscillations' sources precisely and then studying the relationship between oscillatory reactivity and ongoing movement, we recorded stereoelectroencephalograms with intracerebral electrodes in eight epileptic subjects awaiting surgical treatment. The sensorimotor cortex was free of lesions and was exhaustively explored with the electrodes. Subjects were asked to perform various self‐paced movements contralateral to the exploration zone, brief and sustained, distal movements and a pointing movement. We used the event‐related desynchronization method to quantify the reactivity of the 40–60‐Hz band before, during and after the performance of movement. A very focused, event‐related synchronization of gamma rhythms was found in all subjects. It was predominantly observed in the primary sensorimotor area and its distribution was consistent with the functional map established using electrical stimulations. Two different temporal patterns were observed, the event‐related synchronization of gamma rhythms was related either to movement onset or to movement offset but was never recorded before movement. This observation suggests that gamma oscillations are more probably related to movement execution than to motor planning. The different patterns argue in favour of multiple functional roles; it has been shown that gamma oscillations may support the efferent drive to the muscles and here we show that they are also likely to be related to somatosensory integration. We therefore suggest that gamma oscillations in the 40–60‐Hz band may support afferent sensory feedback to the sensorimotor cortex during the performance of movement.
Differential expression of KCC2 accounts for the differential GABA responses between relay and intrinsic neurons in the early postnatal rat olfactory bulb
Authors: Wang Cong , Ohno Koji , Furukawa Tomonori , Ueki Takatoshi , Ikeda Masahiko , Fukuda Atsuo , Sato Kohji
Published: March 2005

The rat olfactory bulb is anatomically immature at birth, and considerable neurogenesis and synaptogenesis are known to take place postnatally. In addition, significant physiological changes have also been reported in this period. For example, granule cell‐mediated inhibition following electrical stimulations to the lateral olfactory tract is robust during the first postnatal week, and then decreases abruptly after the second week. However, the mechanism underlying this enhanced inhibition remains to be elucidated. To know the cause of this phenomenon, we investigated the expression patterns of cation‐Cl– co‐transporters (KCC1, KCC2 and NKCC1) mRNAs, which are responsible for the regulation of [Cl–]i. In addition, responses to γ‐aminobutyric acid (GABA) were measured by gramicidin‐perforated patch‐clamp recordings and Ca2+ imaging using fura‐2. We found that in the early postnatal period, mitral cells expressing KCC2 mRNA were inhibited by GABA, while granule cells lacking KCC2 mRNA expression were depolarized or excited by GABA. These results indicate that transient GABA‐mediated excitation on granule cells might be the main cause of the enhanced inhibition on mitral cells, and suggest that these differential GABA responses between relay and intrinsic neurons play pivotal roles in the early postnatal rat olfactory bulb.
mGluRs induce a long‐term depression in the ventral tegmental area that involves a switch of the subunit composition of AMPA receptors
Authors: Bellone Camilla , Lüscher Christian
Published: March 2005

Excitatory glutamatergic synapses on dopamine (DA) neurons of the ventral tegmental area (VTA) undergo long‐lasting changes during conditioning of natural rewards and in response to drug exposure. It has been suggested that the ensuing context‐dependent behavioural changes are associated with an increased efficacy of synaptic afferents determined by the balance of long‐term potentiation (LTP) and long‐term depression (LTD). However, the molecular nature of the forms of LTP/LTD involved remains elusive. Here, using acute rat brain slices, we describe a form of long‐term depression (LTD) that was engaged by synaptic activity or exogenous agonists activating group I metabotropic glutamate receptors (mGluR) and was sensitive to mGluR1 antagonists. Prior to mGluR‐LTD, AMPAR mediated excitatory postsynaptic currents (EPSCs) showed strong rectification at positive potentials and were sensitive to Joro spider toxin (JST), a selective blocker of GluR2‐lacking AMPARs. After mGluR‐LTD, AMPAR EPSCs had linear current‐voltage relations and became insensitive to JST. We conclude that activation of mGluR1s triggers a redistribution exchanging native receptors for GluR2 containing AMPARs, ultimately causing LTD that may oppose pathological neuroadaptation.
Involvement of rostral prefrontal cortex in selection between stimulus‐oriented and stimulus‐independent thought
Authors: Gilbert Sam J. , Frith Christopher D. , Burgess Paul W.
Published: March 2005

We used functional magnetic resonance imaging to investigate brain activity while healthy subjects performed three different tasks, each of which alternated between: (i) phases relying on stimulus‐oriented thought (i.e. cognitive processes provoked by incoming sensory information); and (ii) phases relying on stimulus‐independent thought (i.e. cognitive processes that were not related to any information in the immediate sensory environment). Within each task, the two phases were matched as closely as possible. In all three tasks, lateral rostral prefrontal cortex was transiently activated by a switch between stimulus‐oriented and stimulus‐independent thought (regardless of the direction of the switch). Medial rostral prefrontal cortex consistently exhibited sustained activity for stimulus‐oriented vs. stimulus‐independent thought. These results suggest the involvement of rostral prefrontal cortex in selection between stimulus‐oriented and stimulus‐independent cognitive processes.
The pharmacokinetics of 400 µg of oral desmopressin in elderly patients with nocturia, and the correlation between the absorption of desmopressin and clinical effect
Authors: Hvistendahl Gitte M. , Riis Anders , Nørgaard Jens P. , Djurhuus Jens C.
Published: March 2005

OBJECTIVE

To investigate the pharmacokinetic profile of oral desmopressin in elderly patients with nocturia, and to analyse any possible correlation between the absorption and clinical effect.

PATIENTS AND METHODS

In all, 32 patients were screened to determine the baseline number of nocturnal voids and the nocturia index; of these, 24 fulfilled the inclusion criteria and were enrolled for a pharmacokinetic evaluation of oral desmopressin 400 µg. A double‐blind, randomized, placebo‐controlled, crossover‐effect evaluation period was then used to test the association between the absorption of desmopressin and pharmacodynamic effect. Serial plasma samples were collected for 8 h for a pharmacokinetic analysis of desmopressin. The pharmacodynamics after an equivalent oral dose before bedtime were assessed by measuring changes in the number of nocturnal voids, time to first nocturnal void and nocturnal diuresis, from placebo to active treatment.

RESULTS

There was a linear relationship between plasma desmopressin at 2 h after dosing and the area under the plasma concentration curve from 0 to infinity (Pearson's ρ 0.923, P < 0.001). Women had a significantly higher plasma desmopressin concentration than men (P = 0.0012) and more adverse events. There was no correlation between plasma desmopressin at 2 h after dosing and the within‐patient response in any of the effect variables. Generally, the number of nocturnal voids and nocturnal diuresis were half that with placebo. The time to the first nocturnal void was almost doubled compared with placebo.

CONCLUSIONS

There seems to be a relationship between gender, plasma level of desmopressin and the incidence of adverse events. Plasma desmopressin at 2 h after dosing cannot be used to predict the pharmacodynamic response, although desmopressin lowers the nocturnal diuresis and the number of nocturnal voids.
Nocturia, depression and antidepressant medication
Authors: Asplund Ragnar , Johansson Susanne , Henriksson Svante , Isacsson Göran
Published: March 2005

OBJECTIVE

To assess the possible relationship between treatment with selective serotonin‐reuptake inhibitors (SSRIs) and the occurrence of nocturia.

SUBJECTS AND METHODS

An unselected group of adult men and women, living in the city of Östersund, Sweden, were sent a postal questionnaire containing questions on somatic and mental health, sleep, sleepiness and nocturia. For depression diagnostics, the Major Depression Inventory (MDI) was used. Prescription data on antidepressant drugs were extracted from a register in the county of Jämtland, Sweden.

RESULTS

The questionnaire was completed by 1375 subjects, of whom 609 (44%) were men; the response rate was 69%. Prescription data were available for all respondents. The mean (sd) age of the men and women participating were 48.0 (18.2) and 50.1 (19.1) years, respectively. Two or more nocturnal micturition episodes were reported in 15.6% of the men and 16.5% of the women. In a multiple logistic regression analysis, independent correlates for two or more nocturnal voids vs no more than one were: age 45–59 years vs <45 (odds ratio 2.9; 95% confidence interval 1.9–4.7); age 60–74 vs <45 (6.0; 3.7–9.8); age > 75 vs <45 (13.4; 7.9–22.6); major depression, yes vs no (4.6; 2.8–7.5); and being on treatment with SSRI, yes vs no (2.2; 1.1–4.5). Gender was deleted by the logistic regression model.

CONCLUSION

Major depression has previously been found to be associated with increased nocturnal micturition. In the present study, twice as many men and women treated with SSRIs as those not so treated had two or more nocturnal voids, after adjusting for major depression and age. The implication for the risk of fall injuries is discussed.
Day‐case sling surgery for stress urinary incontinence: feasibility and safety
Authors: Giri Subhasis K. , Drumm John , Saunders Jean A. , McDonald Jane , Flood Hugh D.
Published: March 2005

OBJECTIVE

To prospectively assess the feasibility for discharge 10 h after a porcine dermal pubovaginal sling procedure (PVS), to examine the surgical factors (postoperative complications) affecting discharge, and to measure the short‐term cure rate for stress urinary incontinence (SUI).

PATIENTS AND METHODS

Between June 2003 and December 2003, 40 consecutive patients with SUI and scheduled for treatment using a porcine dermal sling were enrolled in this prospective study. Patients were admitted with a planned overnight stay and returned to the ward with no urinary catheter. Outcome measures were bladder emptying efficiency (EE) at 10 h after surgery, time intervals to the first three spontaneous voids, EE of the first three voids, time required to achieve an EE of ≥ 75%, a visual analogue scale pain score, perioperative complications, and short‐term cure rate of SUI. Patients were considered suitable for discharge from hospital when the EE was ≥ 75% or when they were self‐catheterizing confidently with adequate pain control and no significant complication. All patients were followed for 6 months.

RESULTS

The median EE at 10 h was 61%; 16 patients (40%) achieved efficient emptying and were suitable for discharge 10 h after surgery. The median intervals to the first three spontaneous voids were 7, 10 and 17 h, and the median EEs for the first three voids 46%, 61% and 75%. The median visual analogue scale pain score was 3.5. Patients with intrinsic sphincter deficiency (ISD) were significantly less likely to achieve efficient emptying at 10 h (39% vs 70%). Overall SUI was cured or improved in 90% of patients at the 6‐month follow‐up.

CONCLUSIONS

In the present study only 40% of patients were suitable for day‐case sling surgery. Early bladder emptying inefficiency was the main limiting factor. Exclusion of patients with ISD and possibly decreasing the EE threshold to 50% would improve the discharge rate. The short‐term results of this PVS are similar to those obtained with the autologous fascial sling.
A stereological analysis of fibrosis and inflammatory reaction induced by four different synthetic slings
Authors: Thiel Marcelo , Rodrigues Palma Paulo C. , Riccetto Cássio L.Z. , Dambros Miriam , Netto Nelson R.
Published: March 2005

OBJECTIVES

To analyse quantitatively, using stereological methods, the density of the collagen fibres induced by four types of sling materials, and verify by a histopathological analysis the corresponding inflammatory reaction, as fibrosis secondary to sling implantation is considered responsible for restoring urethral support and re‐establishing continence in women with stress urinary incontinence, and new synthetic materials that promote adequate fibrosis with the least intensity and duration have been proposed to substitute the aponeurotic sling.

MATERIALS AND METHODS

The study comprised 70 isogenic white Wistar rats divided into three groups: group A (30 rats) had 8 × 4 mm strips of silicone and porcine small intestine submucosa (SIS) implanted in the abdominal subcutaneous tissues; group B (30 rats) had 8 × 4 mm strips of polycaprolactone and polylactic acid copolymers and monofilament polypropylene (PLP) implanted the abdominal subcutaneous layer; while a control group of 10 rats had dissection and suturing with 5/0 Nylon in the abdominal subcutaneous layer, as used to fix the strips in the other rats. Picro‐Sirius staining was used to assess collagen fibres, and haematoxylin‐eosin for the histopathological study. At 7, 30 and 90 days after surgery, 10 rats from each group were killed and assessed.

RESULTS

After 7 days all the materials induced a moderate inflammatory reaction that did not differ from that in the control group. At 30 days there was no difference between the control and polycaprolactone and polylactic acid copolymers, having the least inflammatory reaction. PLP and silicone produced a moderate inflammatory reaction, while the porcine SIS induced a more intense reaction. At 90 days there was a more intense inflammatory reaction in polycaprolactone and polylactic acid copolymers than before but it was less than with PLP and silicone, which again were no different. During this period the inflammatory reaction induced by SIS was greater. The stereological analysis indicated that collagen fibres induced by polycaprolactone and polylactic acid copolymers and PLP were less dense (61% and 65%, respectively), and significantly less than with silicone (85%) and SIS (86%).

CONCLUSION

PLP was the best nonabsorbable material as it induced a less intense inflammatory reaction than the other tested materials. As porcine SIS was completely absorbed the intense fibrosis induced is useful, as it is exclusively responsible for the urethral support later after surgery.
Comparison of laparoscopic and open donor nephrectomy: a randomized controlled trial
Authors: Simforoosh Nasser , Basiri Abbas , Tabibi Ali , Shakhssalim Nasser , Hosseini Moghaddam Seyed M.M.
Published: March 2005

Authors from Iran compare various outcomes between laparoscopic and open donor nephrectomy in kidney transplantation; they carried out a large comparative trial, and found that laparoscopic donor nephrectomy gave better donor satisfaction and morbidity, with equivalent graft outcome.

OBJECTIVE

To compare the graft survival, donor and recipient outcome, donor satisfaction, and complications of laparoscopic (LDN) and open donor nephrectomy (ODN) in kidney transplantation.

PATIENTS AND METHODS

In a randomized controlled trial, 100 cases each of LDN and ODN were compared. We modified the standard LDN procedure to make it less expensive.

RESULTS

The mean (sd) operative duration was 152.2 (33.9) min for ODN and 270.8 (58.5) min for LDN, and the mean duration of kidney warm ischaemia was 1.87 min for ODN and 8.7 min for LDN. Only one LDN required conversion to ODN because of bleeding. The mean follow‐up in the LDN and ODN groups was not significantly different (406.1 vs 403.8 days). The mean (sd) score for donor satisfaction was 17.3 (3.5) for ODN and 19.6 (1.0) for LDN. The rate of ureteric complications was 2% for ODN and none for LDN. As determined by serum creatinine levels at 3, 21–30, 90, 180 and 365 days after surgery, graft function was not significantly different between ODN and LDN. Long‐term graft survival was 93.8% for LDN and 92.7% for ODN.

CONCLUSIONS

Compared to ODN, LDN was associated with greater donor satisfaction, less morbidity and equivalent graft outcome.
Differential regulation of estrogen receptor alpha, glucocorticoid receptor and retinoic acid receptor alpha transcriptional activity by melatonin is mediated via different G proteins
Authors: Kiefer Todd L. , Lai Ling , Yuan Lin , Dong Chunmin , Burow Matthew E. , Hill Steven M.
Published: March 2005

Abstract:  Melatonin has been shown to bind to the MT1 G protein‐coupled receptor (GPCR) in MCF‐7 breast cancer cells to modulate the estrogen response pathway suppressing estrogen‐induced estrogen receptor alpha (ERα) transcriptional activity, blunting ER/DNA binding activity and suppressing cell proliferation. In these studies we have examined the effect of melatonin on the transcriptional activity of the ERα and other members of the steroid/thyroid hormone receptor superfamily, namely, the glucocorticoid receptor (GR) and the retinoic acid receptor alpha (RARα). As with the ERα, melatonin represses ligand (dexamethasone)‐induced activation of the GR. This effect of melatonin on ERα and GR is blocked by pertussis toxin (PTX) suggesting that melatonin's actions may be mediated via a PTX‐sensitive Gαi protein. In contrast, melatonin potentiates the action of all‐trans‐retinoic acid on RARα transcriptional activation and enhances RARα/DNA binding activity, an action which is not PTX‐sensitive. Expression of a dominant‐positive Gαi2 protein, with which the MT1 receptor has been shown to couple, is able to mimic the effect of melatonin on ERα but not RARα transcriptional activation in breast cancer cells. This demonstrates that GPCRs can modulate the transcriptional activity of various steroid receptors in response to their ligand through activation of different G protein signaling pathways.