bluuebunny/crossref_metadata_2025_split huggingface dataset:
A pilot study of genetic differentiation between two phenotypes of a Mediterranean population of the bivalve Cerastoderma glaucum and genetic discrimination with other Cerastoderma glaucum and Cerastoderma edule populations outside the Mediterranean
Authors: Ladhar‐Chaabouni Rim , Hamza‐Chaffai Amel , Hardivillier Yann , Chénais Benoît , Denis Françoise 
Published: November 2009

AbstractThe internal transcribed spacer 1 (ITS1) region of 29 individuals of Cerastoderma glaucum (from the Mediterranean Sea, the Atlantic and the North Sea) and 18 individuals of Cerastoderma edule (from the Atlantic and the North Sea) and the cytochrome c oxidase subunit I (COI) region of 43 individuals of C. glaucum (from the Mediterranean Sea, the Atlantic and the North Sea) and 9 individuals of C. edule (from the Atlantic and the North Sea) were PCR amplified and sequenced. The ITS1 sequences led us to describe 27 genetic haplotypes, while 21 genetic haplotypes were determined via the COI sequences. The ITS1 and the COI sequences revealed an important genetic variability within the Mediterranean population of C. glaucum, which contained two different phenotypes: orange foot and yellow foot. A genetic differentiation between the two phenotypes was revealed by the nucleotide diversity index (π) and is strengthened by the AMOVA analysis. This result leads us to suspect the presence of two different groups in the same population of C. glaucum. Nevertheless to be confirmed this hypothesis requires further studies using more locations and a larger number of sample sizes.
Parvalbumin‐containing neurons, perineuronal nets and experience‐dependent plasticity in murine barrel cortex
Authors: Nowicka Dorota , Soulsby Susan , Skangiel‐Kramska Jolanta , Glazewski Stanislaw 
Published: November 2009

AbstractThe ability to undergo experience‐dependent plasticity in the neocortex is often limited to early development, but also to particular cortical loci and specific experience. In layers II–IV of the barrel cortex, plasticity evoked by removing all but one vibrissae (univibrissa rearing) does not have a time limit except for layer IV barrels, where it can only be induced during the first postnatal week. In contrast, deprivation of every second vibrissa (chessboard deprivation) removes time limits for plasticity. The mechanism permitting plasticity in response to chessboard deprivation and halting it in reply to univibrissa rearing is unknown. Condensation of chondroitin sulfate proteoglycans into perineuronal nets and an increase in intracortical inhibition mediated by parvalbumin‐containing interneurons are implicated in closing the critical period for ocular dominance plasticity. These factors could also be involved in setting up the critical period in barrels in a way that depends on a particular sensory experience. We therefore examined changes in density of parvalbumin‐containing cells and perineuronal nets during development of mouse barrel cortex and after brief univibrissa and chessboard experience in adolescence. We observed a progressive increase in the density of the two markers across cortical layers between postnatal day 10 and 20, which was especially pronounced in the barrels. Univibrissa rearing, but not chessboard deprivation, increased the density of perineuronal nets and parvalbumin‐containing cells in the deprived barrels, but only those that immediately neighbour the undeprived barrel. These data suggest the involvement of both tested factors in closing the critical period in barrels in an experience‐dependent manner.
Neural correlates of conflict resolution between automatic and volitional actions by basal ganglia
Authors: Watanabe Masayuki , Munoz Douglas P. 
Published: November 2009

AbstractA dominant basal ganglia (BG) model consists of two functionally opposite pathways: one facilitates motor output and the other suppresses it. Although this idea was originally proposed to account for motor deficits, it has been extended recently also to explain cognitive deficits. Here, we employed the antisaccade paradigm (look away from a stimulus) to address the role of the caudate nucleus, the main BG input stage where the two pathways diverge, in conflict resolution. Using single neuron recordings in awake monkeys, we identified the following three groups of neurons. The first group of neurons showed activity consistent with sensory‐driven (automatic) saccades toward a contralateral visual stimulus. The second group of neurons showed activity consistent with internally driven (volitional) saccades toward the contralateral side regardless of stimulus locations. The third group of neurons showed similar firing characteristics with the second group of neurons, except that their preferred saccade direction was ipsilateral. The activity of the three groups of neurons was correlated with behavioral outcome. Based on these findings, we suggest the following hypothesis: the first and second groups of neurons encoding automatic and volitional saccades, respectively, might give rise to the facilitation (direct) pathway and promote saccades toward the opposite directions, which creates a response conflict. This conflict could be resolved by the third group of caudate neurons, which might give rise to the suppression (indirect) pathway and attenuate inappropriate saccade commands toward the stimulus.
Dopamine–oxytocin interactions in penile erection
Authors: Baskerville T. A. , Allard J. , Wayman C. , Douglas A. J. 
Published: November 2009

AbstractDopamine and oxytocin have established roles in the central regulation of penile erection in rats; however, the neural circuitries involved in a specific erectile context and the interaction between dopamine and oxytocin mechanisms remain to be elucidated. The medial preoptic area (MPOA), supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus may serve as candidate sites because they contain oxytocin cells, receive dopaminergic inputs and have been implicated in mediating masculine sexual behavior. Double immunofluorescence revealed that substantial numbers of oxytocin cells in the MPOA, SON and PVN possess dopamine D2, D3 and D4 receptors. In anaesthetized rats, using intracavernous pressure as a physiological indicator of erection, blockade of lumbosacral oxytocin receptors (UK, 427843) reduced erectile responses to a nonselective dopamine agonist (apomorphine), suggesting that dopamine recruits a paraventriculospinal oxytocin pathway. In conscious males in the absence of a female, penile erection elicited by a D2/D3 (Quinelorane) but not D4 (PD168077) agonist was associated with activation of medial parvocellular PVN oxytocin cells. In another experiment where males were given full access to a receptive female, a D4 (L‐745870) but not D2 or D3 antagonist (L‐741626; nafadotride) inhibited penile erection (intromission), and this was correlated with SON magnocellular oxytocin neuron activation. Together, the data suggest dopamine’s effects on hypothalamic oxytocin cells during penile erection are context‐specific. Dopamine may act via different parvocellular and magnocellular oxytocin subpopulations to elicit erectile responses, depending upon whether intromission is performed. This study demonstrates the potential existence of interaction between central dopamine and oxytocin pathways during penile erection, with the SON and PVN serving as integrative sites.
Long‐term synaptic plasticity is impaired in rats with lesions of the ventrolateral preoptic nucleus
Authors: Arrigoni Elda , Lu Jun , Vetrivelan Ramalingam , Saper Clifford B. 
Published: November 2009

AbstractImpairment of memory functions has been frequently reported in models of sleep deprivation. Similarly, hippocampal long‐term synaptic plasticity has been shown to be sensitive to sleep loss caused by acute sleep restriction. However, such approaches are limited by the stressful nature of sleep deprivation, and because it is difficult to study long‐term sleep restriction in animals. Here, we report the effects of chronic sleep loss on hippocampal long‐term potentiation (LTP) in a rodent model of chronic partial sleep deprivation. We studied LTP of the Schaffer collateral–CA1 synapses in hippocampal slices prepared from rats with lesions of the ventrolateral preoptic nucleus (VLPO), which suffered reductions in total sleep time for several weeks after lesions. In slices prepared from VLPO‐lesioned rats, LTP was impaired proportionally to the amount of sleep loss, and the decline in LTP followed a single exponential function over the amount of accumulated sleep debt. As compared with sham‐lesioned controls, hippocampal slices from VLPO‐lesioned rats showed a greater response to adenosine antagonists and greater paired‐pulse facilitation (PPF). However, exogenous adenosine depressed evoked synaptic transmission and increased PPF in VLPO‐lesioned and sham‐lesioned rats by equal amounts, suggesting that the greater endogenous adenosine inhibitory tone in the VLPO‐lesioned rats is associated with greater ligand accumulation rather than a change in adenosine receptor sensitivity or adenosine‐mediated neurotransmitter release probability. LTP in VLPO‐lesioned animals was partially restored by adenosine antagonists, suggesting that adenosine accumulation in VLPO‐lesioned animals could account for some of the observed synaptic plasticity deficits.
Extinction of cued fear memory involves a distinct form of depotentiation at cortical input synapses onto the lateral amygdala
Authors: Hong Ingie , Song Beomjong , Lee Sukwon , Kim Jihye , Kim Jeongyeon , Choi Sukwoo 
Published: November 2009

AbstractThe amygdala is known to be a critical storage site of conditioned fear memory. Among the two major pathways to the lateral amygdala (LA), the cortical pathway is known to display a presynaptic long‐term potentiation which is occluded with fear conditioning. Here we show that fear extinction results in a net depression of conditioning‐induced potentiation at cortical input synapses onto the LA (C‐LA synapses). Fear conditioning induced a significant potentiation of excitatory postsynaptic currents at C‐LA synapses compared with naïve and unpaired controls, whereas extinction apparently reversed this potentiation. Paired‐pulse low‐frequency stimulation (pp‐LFS) induced synaptic depression in the C‐LA pathway of fear‐conditioned rats, but not in naïve or unpaired controls, indicating that the pp‐LFS‐induced depression is specific to associative learning‐induced changes (pp‐LFS‐induced depotentiationex vivo). Importantly, extinction occluded pp‐LFS‐induced depotentiationex vivo, suggesting that extinction shares some mechanisms with the depotentiation. pp‐LFS‐induced depotentiationex vivo required NMDA receptor (NMDAR) activity, consistent with a previous finding that blockade of amygdala NMDARs impaired fear extinction. In addition, pp‐LFS‐induced depotentiationex vivo required activity of group II metabotropic glutamate receptors (mGluRs), known to be present at presynaptic terminals, but not AMPAR internalization, consistent with a presynaptic mechanism for pp‐LFS‐induced depotentiationex vivo. This result is in contrast with another form of ex vivo depotentiation in the thalamic pathway that requires both group I mGluR activity and AMPAR internalization. We thus suggest that extinction of conditioned fear involves a distinct form of depotentiation at C‐LA synapses, which depends upon both NMDARs and group II mGluRs.
Embryonic striatal grafts restore bi‐directional synaptic plasticity in a rodent model of Huntington’s disease
Authors: Mazzocchi‐Jones David , Döbrössy Máté , Dunnett Stephen B. 
Published: November 2009

AbstractEmbryonic striatal grafts integrate with the host striatal circuitry, forming anatomically appropriate connections capable of influencing host behaviour. In addition, striatal grafts can influence host behaviour via a variety of non‐specific, trophic and pharmacological mechanisms; however, direct evidence that recovery is dependent on circuit reconstruction is lacking. Recent studies suggest that striatal grafts alleviate simple motor deficits, and also that learning of complex motor skills and habits can also be restored. However, although the data suggest that such ‘re‐learning’ requires integration of the graft into the host striatal circuitry, little evidence exists to demonstrate that such integration includes functional synaptic connections. Here we demonstrate that embryonic striatal grafts form functional connections with the host striatal circuitry, capable of restoring stable synaptic transmission, within an excitotoxic lesion model of Huntington’s disease. Furthermore, such ‘functional integration’ of the striatal graft enables the expression of host–graft bi‐directional synaptic plasticity, similar to the normal cortico‐striatal circuit. These results indicate that striatal grafts express synaptic correlates of learning, and thereby provide direct evidence of functional neuronal circuit repair, an essential component of ‘functional integration’.
Activity‐driven mobilization of post‐synaptic proteins
Authors: Gutiérrez R. Carolina , Flynn Robyn , Hung Johanna , Kertesz Audrey C. , Sullivan Andrea , Zamponi Gerald W. , El‐Husseini Alaa , Colicos Michael A. 
Published: November 2009

AbstractSynapses established during central nervous system development can be modified through synapse elimination and formation. These processes are, in part, activity dependent and require regulated trafficking of post‐synaptic components. Here, we investigate the activity‐driven remodeling of cultured rat hippocampal neurons at 14 days in vitro, focusing on the post‐synaptic proteins PSD‐95, Shank, neuroligin (NL)1 and actin. Using live imaging and photoconductive stimulation, we found that high‐frequency activity altered the trajectory, but not velocity, of PSD‐95‐GFP and Shank‐YFP clusters, whereas it reduced the speed and increased the number of NL1 clusters. Actin‐CFP reorganized into puncta following activity and ∼50% of new puncta colocalized with NL1 clusters. Actin reorganization was enhanced by the overexpression of NL1 and decreased by the expression of an NL1 mutant, NL1‐R473C. These results demonstrate activity‐dependent changes that may result in the formation of new post‐synaptic sites and suggest that NL1 modulates actin reorganization. The results also suggest that a common mechanism underlies both the developmental and activity‐dependent remodeling of excitatory synapses.
The relation of ventromedial prefrontal cortex activity and heart rate fluctuations at rest
Authors: Ziegler Gabriel , Dahnke Robert , Yeragani Vikram K. , Bär Karl‐Jürgen 
Published: November 2009

AbstractRecent studies applying functional magnetic resonance imaging have focused on the description of cerebral substrates of changes in cardiac function during diverse autonomic maneuvers or stressful cognitive tasks. These studies might be limited by the indistinguishable neuronal activity due to cognitive processes, which are known to influence autonomic function, and the ‘baseline’ activity in the central autonomic network. We therefore investigated 26 healthy volunteers in the magnetic resonance scanner to simultaneously obtain functional brain images and RR intervals (intervals between ventricular depolarizations) of the high‐resolution electrocardiogram. The mean RR interval length within each functional scan was computed, which was finally convolved with the canonical hemodynamic response function to obtain a regressor for the functional time series. The resulting individual contrast image indicated a positive covariation of the blood oxygen level‐dependent signal and RR interval length in the ventromedial prefrontal cortex (vmPFC). Furthermore, a reduced mean cross‐approximate entropy value was shown for the interaction between the vmPFC and individual RR intervals. This suggests reduced asynchrony between the heart rate and vmPFC activity in contrast to other brain areas. Our findings confirm data obtained in animals describing the vmPFC as an important forebrain structure of the central autonomic network and an influence of the vmPFC in the cortical generation of efferent vagal activity. This finding needs to be investigated in diseases with known suppression of efferent vagal modulation.
Engineering neuronal nicotinic acetylcholine receptors with functional sensitivity to α‐bungarotoxin: a novel α3‐knock‐in mouse
Authors: Caffery Philip M. , Krishnaswamy Arjun , Sanders Tanya , Liu Jing , Hartlaub Hilary , Klysik Jan , Cooper Ellis , Hawrot Edward 
Published: November 2009

AbstractWe report here the construction of a novel knock‐in mouse expressing chimeric α3 nicotinic acetylcholine receptor (nAChR) subunits with pharmacological sensitivity to α‐bungarotoxin (αBTX). Sensitivity was generated by substituting five amino acids in the loop C (β9–β10) region of the mouse α3 subunit with the corresponding residues from the α1 subunit of the muscle type receptor from Torpedo californica. To demonstrate the utility of the underlying concept, expressed α3[5] subunits were characterized in the superior cervical ganglia (SCG) of homozygous knock‐in mice, where the synaptic architecture of postsynaptic α3‐containing nAChR clusters could now, for the first time, be directly visualized and interrogated by live‐staining with rhodamine‐conjugated αBTX. Consistent with the postsynaptic localization of ganglionic nAChRs, the αBTX‐labeled puncta colocalized with a marker for synaptic varicosities. Following in vivo deafferentation, these puncta persisted but with significant changes in intensity and distribution that varied with the length of the recovery period. Compound action potentials and excitatory postsynaptic potentials recorded from SCG of mice homozygous for α3[5] were abolished by 100 nmαBTX, even in an α7 null background, demonstrating that synaptic throughput in the SCG is completely dependent on the α3‐subunit. In addition, we observed that the genetic background of various inbred and outbred mouse lines greatly affects the functional expression of α3[5]‐nAChRs, suggesting a powerful new approach for exploring the molecular mechanisms underlying receptor assembly and trafficking. As αBTX‐sensitive sequences can be readily introduced into other nicotinic receptor subunits normally insensitive to αBTX, the findings described here should be applicable to many other receptors.
Efficacy and safety of monotherapy of sitagliptin compared with metformin in patients with type 2 diabetes
Authors: Aschner P. , Katzeff H. L. , Guo H. , Sunga S. , Williams‐Herman D. , Kaufman K. D. , Goldstein B. J. ,   for the Sitagliptin Study 049 Group
Published: November 2009

Aim: To compare the efficacy and safety of monotherapy with sitagliptin and metformin in treatment‐naïve patients with type 2 diabetes. Methods: In a double‐blind study, 1050 treatment‐naïve patients (i.e. not taking an antihyperglycaemic agent for ≥16 weeks prior to study entry) with type 2 diabetes and an HbA1c 6.5–9% were randomized (1:1) to treatment with once‐daily sitagliptin 100 mg (N = 528) or twice‐daily metformin 1000 mg (N = 522) for 24 weeks. Metformin was up‐titrated from 500 to 2000 mg per day (or maximum tolerated daily dose ≥1000 mg) over a period of 5 weeks. The primary analysis used a per‐protocol (PP) approach to assess whether sitagliptin was non‐inferior to metformin based on HbA1c change from baseline at week 24. Non‐inferiority was to be declared if the upper boundary of the 95% confidence interval (CI) for the between‐group difference in this endpoint was <0.40%. Results: From a mean baseline HbA1c of 7.2% in the PP population, HbA1c change from baseline was −0.43% with sitagliptin (n = 455) and −0.57% with metformin (n = 439). The between‐group difference (95% CI) was 0.14% (0.06, 0.21), thus confirming non‐inferiority. Baseline HbA1c influenced treatment response, with larger reductions in HbA1c observed in patients with baseline HbA1c≥8% in the sitagliptin (–1.13%; n = 74) and metformin (–1.24%; n = 73) groups. The proportions of patients at week 24 with HbA1c values at the goals of <7 or <6.5% were 69 and 34% with sitagliptin and 76 and 39% with metformin, respectively. Fasting plasma glucose changes from baseline were −11.5 mg/dL (–0.6 mmol/l) and −19.4 mg/dl (–1.1 mmol/l) with sitagliptin and metformin, respectively (difference in LS mean change from baseline [95% CI] = 8.0 mg /dl [4.5,11.4]). Both treatments led to similar improvements from baseline in measures of homeostasis model assessment‐β cell function (HOMA‐β) and insulin resistance (HOMA‐IR). The incidence of hypoglycaemia was 1.7% with sitagliptin and 3.3% with metformin (p = 0.116). The incidence of gastrointestinal‐related adverse experiences was substantially lower with sitagliptin (11.6%) compared with metformin (20.7%) (difference in incidence [95% CI] = −9.1% [−13.6,−4.7]), primarily because of significantly decreased incidences of diarrhoea (3.6 vs. 10.9%; p < 0.001) and nausea (1.1 vs. 3.1%; p = 0.032). Body weight was reduced from baseline with both sitagliptin (LS mean change [95% CI] = −0.6 kg [−0.9,−0.4]) and metformin (–1.9 kg [–2.2, −1.7]) (p < 0.001 for sitagliptin vs. metformin). Conclusions: In this 24‐week monotherapy study, sitagliptin was non‐inferior to metformin in improving HbA1c in treatment‐naïve patients with type 2 diabetes. Although both treatments were generally well tolerated, a lower incidence of gastrointestinal‐related adverse experiences was observed with sitagliptin.
A one‐year study to assess the safety and efficacy of the CB1R inverse agonist taranabant in overweight and obese patients with type 2 diabetes
Authors: Kipnes M. S. , Hollander P. , Fujioka K. , Gantz I. , Seck T. , Erondu N. , Shentu Y. , Lu K. , Suryawanshi S. , Chou M. , Johnson‐Levonas A. O. , Heymsfield S. B. , Shapiro D. , Kaufman K. D. , Amatruda J. M. 
Published: November 2009

Aim: To evaluate the efficacy and safety of taranabant in overweight and obese patients with type 2 diabetes mellitus (T2DM). Methods: This was a multicenter, double‐blind, randomized, placebo‐controlled study in overweight and obese patients with T2DM (ages ≥ 18 and ≤ 75 years) with a BMI ≥ 27 kg/m2 and ≤ 43 kg/m2 and HbA1c ≥7.0 and ≤ 10.0%, who were either not on an antihyperglycaemic agent or on a stable dose of metformin (≥ 1500 mg/day). After a 2‐week placebo run‐in, patients were randomized to placebo (N = 156) or taranabant 0.5‐mg (N = 155), 1‐mg (N = 157), or 2‐mg (N = 155) once daily for 52 weeks. Primary efficacy endpoints were changes from baseline in body weight (BW) and HbA1c at Week 36, with results at Week 52 being key secondary endpoints. Results: In the all‐patients‐treated population, using a last‐observation‐carried‐forward analysis, reductions in BW were −2.5, −3.7, −4.5 and −5.1 kg at Week 36 and −2.4, −4.0, −4.6 and −5.3 kg at Week 52 in the placebo, 0.5‐, 1‐ and 2‐mg groups, respectively (all doses significant vs. placebo at both time points). The proportion of patients who lost ≥ 5 and ≥ 10% of their baseline BW was significantly greater in the 1‐ and 2‐mg groups vs. placebo at Week 36 and all taranabant groups vs. placebo at Week 52. Reductions in HbA1c were −0.40, −0.47, −0.68 and −0.71% at Week 36 and −0.30, −0.43, −0.65 and −0.64% at Week 52, in the placebo, 0.5‐, 1‐ and 2‐mg groups, respectively (1‐ and 2‐mg doses significant vs. placebo at both time points). After 52 weeks, the incidences of adverse experiences classified in the gastrointestinal (diarrhoea, nausea, vomiting), nervous system‐related (dizziness, sensory‐related), and psychiatric (irritability, depression‐related) organ systems were numerically higher or statistically significantly higher in all taranabant groups compared with the placebo group. Conclusions: After 36 and 52 weeks, treatment with taranabant at the 1‐ and 2‐mg doses led to clinically significant weight loss and improvement in glycaemic parameters in overweight and obese patients with T2DM that was associated with dose‐related increases in adverse experiences. Based on these data and data from other Phase III clinical studies, it was determined that the overall safety and efficacy profile of taranabant did not support further development for the treatment of obesity.