Williams S

References (9)

Title : Resting skeletal muscle PNPLA2 (ATGL) and CPT1B are associated with peak fat oxidation rates in men and women but do not explain observed sex differences - Chrzanowski-Smith_2021_Exp.Physiol_106_1208
Author(s) : Chrzanowski-Smith OJ , Edinburgh RM , Smith E , Thomas MP , Walhin JP , Koumanov F , Williams S , Betts JA , Gonzalez JT
Ref : Exp Physiol , 106 :1208 , 2021
Abstract : NEW FINDINGS: What is the central question of this study? What is the relationship between proteins in skeletal muscle and adipose tissue determined at rest and at peak rates of fat oxidation in men and women? What is the main finding and its importance? The resting contents of proteins in skeletal muscle involved in triglyceride hydrolysis and mitochondrial lipid transport were more strongly associated with peak fat oxidation rates than proteins related to lipid transport or hydrolysis in adipose tissue. Although females displayed higher relative rates of fat oxidation than males, this was not explained by the proteins measured in this study, suggesting that other factors determine sex differences in fat metabolism. ABSTRACT: We explored key proteins involved in fat metabolism that might be associated with peak fat oxidation (PFO) and account for sexual dimorphism in fuel metabolism during exercise. Thirty-six healthy adults [15 women; 40 +/- 11 years of age; peak oxygen consumption 42.5 +/- 9.5 ml (kg body mass)(-1) min(-1) ; mean +/- SD] completed two exercise tests to determine PFO via indirect calorimetry. Resting adipose tissue and/or skeletal muscle biopsies were obtained to determine the adipose tissue protein content of PLIN1, ABHD5 (CGI-58), LIPE (HSL), PNPLA2 (ATGL), ACSL1, CPT1B and oestrogen receptor alpha (ERalpha) and the skeletal muscle protein content of FABP 3 (FABPpm), PNPLA2 (ATGL), ACSL1, CTP1B and ESR1 (ERalpha). Moderate strength correlations were found between PFO [in milligrams per kilogram of fat-free mass (FFM) per minute] and the protein content of PNPLA2 (ATGL) [r(s) = 0.41 (0.03-0.68), P < 0.05] and CPT1B [r(s) = 0.45 (0.09-0.71), P < 0.05] in skeletal muscle. No other statistically significant bivariate correlations were found consistently. Females had a greater relative PFO than males [7.1 +/- 1.9 vs. 4.5 +/- 1.3 and 7.3 +/- 1.7 vs. 4.8 +/- 1.2 mg (kg FFM)(-1) min(-1) in the adipose tissue (n = 14) and skeletal muscle (n = 12) subgroups, respectively (P < 0.05)]. No statistically significant sex differences were found in the content of these proteins. The regulation of PFO might involve processes relating to intramyocellular triglyceride hydrolysis and mitochondrial fatty acid transport, and adipose tissue is likely to play a more minor role than muscle. Sex differences in fat metabolism are likely to be attributable to factors other than the resting content of proteins in skeletal muscle and adipose tissue relating to triglyceride hydrolysis and fatty acid transport.
ESTHER : Chrzanowski-Smith_2021_Exp.Physiol_106_1208
PubMedSearch : Chrzanowski-Smith_2021_Exp.Physiol_106_1208
PubMedID: 33675111

Title : Enhancement of attentional performance by selective stimulation of alpha4beta2(*) nAChRs: underlying cholinergic mechanisms - Howe_2010_Neuropsychopharmacology_35_1391
Author(s) : Howe WM , Ji J , Parikh V , Williams S , Mocaer E , Trocme-Thibierge C , Sarter M
Ref : Neuropsychopharmacology , 35 :1391 , 2010
Abstract : Impairments in attention are a major component of the cognitive symptoms of neuropsychiatric and neurodegenerative disorders. Using an operant sustained attention task (SAT), including a distractor condition (dSAT), we assessed the putative pro-attentional effects of the selective alpha4beta2(*) nicotinic acetylcholine receptor (nAChR) agonist S 38232 in comparison with the non-selective agonist nicotine. Neither drug benefited SAT performance. However, in interaction with the increased task demands implemented by distractor presentation, the selective agonist, but not nicotine, enhanced the detection of signals during the post-distractor recovery period. This effect is consistent with the hypothesis that second-long increases in cholinergic activity ('transients') mediate the detection of cues and that nAChR agonists augment such transients. Electrochemical recordings of prefrontal cholinergic transients evoked by S 38232 and nicotine indicated that the alpha4beta2(*) nAChR agonist evoked cholinergic transients that were characterized by a faster rise time and more rapid decay than those evoked by nicotine. Blockade of the alpha7 nAChR 'sharpens' nicotine-evoked transients; therefore, we determined the effects of co-administration of nicotine and the alpha7 nAChR antagonist methyllycaconitine on dSAT performance. Compared with vehicle and nicotine alone, this combined treatment significantly enhanced the detection of signals. These results indicate that compared with nicotine, alpha4beta2(*) nAChR agonists significantly enhance attentional performance and that the dSAT represents a useful behavioral screening tool. The combined behavioral and electrochemical evidence supports the hypothesis that nAChR agonist-evoked cholinergic transients, which are characterized by rapid rise time and fast decay, predict robust drug-induced enhancement of attentional performance.
ESTHER : Howe_2010_Neuropsychopharmacology_35_1391
PubMedSearch : Howe_2010_Neuropsychopharmacology_35_1391
PubMedID: 20147893

Title : Distinct electrophysiological properties of glutamatergic, cholinergic and GABAergic rat septohippocampal neurons: novel implications for hippocampal rhythmicity - Sotty_2003_J.Physiol_551_927
Author(s) : Sotty F , Danik M , Manseau F , Laplante F , Quirion R , Williams S
Ref : Journal of Physiology , 551 :927 , 2003
Abstract : The medial septum-diagonal band complex (MSDB) contains cholinergic and non-cholinergic neurons known to play key roles in learning and memory processing, and in the generation of hippocampal theta rhythm. Electrophysiologically, several classes of neurons have been described in the MSDB, but their chemical identity remains to be fully established. By combining electrophysiology with single-cell RT-PCR, we have identified four classes of neurons in the MSDB in vitro. The first class displayed slow-firing and little or no Ih, and expressed choline acetyl-transferase mRNA (ChAT). The second class was fast-firing, had a substantial Ih and expressed glutamic acid decarboxylase 67 mRNA (GAD67), sometimes co-localized with ChAT mRNAs. A third class exhibited fast- and burst-firing, had an important Ih and expressed GAD67 mRNA also occasionally co-localized with ChAT mRNAs. The ionic mechanism underlying the bursts involved a low-threshold spike and a prominent Ih current, conductances often associated with pacemaker activity. Interestingly, we identified a fourth class that expressed transcripts solely for one or two of the vesicular glutamate transporters (VGLUT1 and VGLUT2), but not ChAT or GAD. Some putative glutamatergic neurons displayed electrophysiological properties similar to ChAT-positive slow-firing neurons such as the occurrence of a very small Ih, but nearly half of glutamatergic neurons exhibited cluster firing with intrinsically generated voltage-dependent subthreshold membrane oscillations. Neurons belonging to each of the four described classes were found among septohippocampal neurons by retrograde labelling. We provide results suggesting that slow-firing cholinergic, fast-firing and burst-firing GABAergic, and cluster-firing glutamatergic neurons, may each uniquely contribute to hippocampal rhythmicity in vivo.
ESTHER : Sotty_2003_J.Physiol_551_927
PubMedSearch : Sotty_2003_J.Physiol_551_927
PubMedID: 12865506

Title : Widely expressed transcripts for chemokine receptor CXCR1 in identified glutamatergic, gamma-aminobutyric acidergic, and cholinergic neurons and astrocytes of the rat brain: a single-cell reverse transcription-multiplex polymerase chain reaction study - Danik_2003_J.Neurosci.Res_74_286
Author(s) : Danik M , Puma C , Quirion R , Williams S
Ref : Journal of Neuroscience Research , 74 :286 , 2003
Abstract : Increasing evidence suggests that the chemokine interleukin (IL)-8/CXCL8 plays important roles in CNS development, neuronal survival, modulation of excitability, and neuroimmune response. Recently, we have shown that CXCL8 can acutely modulate ion channel activity in septal neurons expressing receptors CXCR1 and/or CXCR2. This was a surprising finding, insofar as CXCR1 expression had not been described for the mammalian brain. Here we investigated whether CXCR1 transcripts are present in other brain regions, whether they are expressed at the single-cell level in molecularly identified neurons and astrocytes, and how they are regulated during early postnatal development. In addition, possible cellular colocalization of CXCR1 and CXCR2 transcripts was examined. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) revealed that CXCR1 mRNAs were expressed in the septum, striatum, hippocampus, cerebellum, and cortex (temporoparietal and entorhinal) at different levels and appeared to be regulated independently from CXCR2 during development. By using RT multiplex PCR on acutely dissociated cells from these brain regions, we show that CXCR1 transcripts were expressed in 83% of 84 sampled neurons displaying cholinergic (choline acetyltransferase mRNAs), gamma-aminobutyric acidergic (glutamic acid decarboxylases 65 and 67 mRNAs), or glutamatergic (vesicular glutamate transporters 1 and 2 mRNAs) phenotypes. CXCR1 and CXCR2 transcripts were colocalized in 45% of neurons sampled and also were present in some glial fibrillary acidic protein mRNA-expressing astrocytes. This is the first study to demonstrate the widespread expression of CXCR1 transcripts in the brain and suggests that CXCR1 may have hitherto unsuspected roles in neuromodulation and inflammation.
ESTHER : Danik_2003_J.Neurosci.Res_74_286
PubMedSearch : Danik_2003_J.Neurosci.Res_74_286
PubMedID: 14515358

Title : PET imaging of brain acetylcholinesterase using [11C]CP-126,998, a brain selective enzyme inhibitor - Bencherif_2002_Synapse_45_1
Author(s) : Bencherif B , Endres CJ , Musachio JL , Villalobos A , Hilton J , Scheffel U , Dannals RF , Williams S , Frost JJ
Ref : Synapse , 45 :1 , 2002
Abstract : PET and [(11)C]CP-126,998, an N-benzylpiperidinebenzisoxazole, were used to image brain acetylcholinesterase (AChE) distribution in healthy controls before and after administration of 5 mg donepezil p.o., a reversible AChE inhibitor. Logan plots were used to compute distribution volumes (V(T)). The V(T) of [(11)C]CP-126,998 was highest in the basal ganglia and cerebellum and lowest in the cerebral cortex, thalamus, amygdala, and hippocampus. The regional V(T) values correlated well with AChE concentration measured in vitro. Donepezil, given 4 h before PET scanning, induced a substantial inhibition of [(11)C]CP-126,998 binding (43-62%) in all brain regions when compared to the baseline PET study. The results of this study indicate that PET imaging of [(11)C]CP-126,998 may be useful in quantifying the distribution of regional brain AChE. This new PET radiotracer may potentially be employed in the diagnosis and treatment of patients with disorders of cholinergic neurotransmission, such as Alzheimer's disease.
ESTHER : Bencherif_2002_Synapse_45_1
PubMedSearch : Bencherif_2002_Synapse_45_1
PubMedID: 12112408

Title : The sequence of the human genome - Venter_2001_Science_291_1304
Author(s) : Venter JC , Adams MD , Myers EW , Li PW , Mural RJ , Sutton GG , Smith HO , Yandell M , Evans CA , Holt RA , Gocayne JD , Amanatides P , Ballew RM , Huson DH , Wortman JR , Zhang Q , Kodira CD , Zheng XH , Chen L , Skupski M , Subramanian G , Thomas PD , Zhang J , Gabor Miklos GL , Nelson C , Broder S , Clark AG , Nadeau J , McKusick VA , Zinder N , Levine AJ , Roberts RJ , Simon M , Slayman C , Hunkapiller M , Bolanos R , Delcher A , Dew I , Fasulo D , Flanigan M , Florea L , Halpern A , Hannenhalli S , Kravitz S , Levy S , Mobarry C , Reinert K , Remington K , Abu-Threideh J , Beasley E , Biddick K , Bonazzi V , Brandon R , Cargill M , Chandramouliswaran I , Charlab R , Chaturvedi K , Deng Z , Di Francesco V , Dunn P , Eilbeck K , Evangelista C , Gabrielian AE , Gan W , Ge W , Gong F , Gu Z , Guan P , Heiman TJ , Higgins ME , Ji RR , Ke Z , Ketchum KA , Lai Z , Lei Y , Li Z , Li J , Liang Y , Lin X , Lu F , Merkulov GV , Milshina N , Moore HM , Naik AK , Narayan VA , Neelam B , Nusskern D , Rusch DB , Salzberg S , Shao W , Shue B , Sun J , Wang Z , Wang A , Wang X , Wang J , Wei M , Wides R , Xiao C , Yan C , Yao A , Ye J , Zhan M , Zhang W , Zhang H , Zhao Q , Zheng L , Zhong F , Zhong W , Zhu S , Zhao S , Gilbert D , Baumhueter S , Spier G , Carter C , Cravchik A , Woodage T , Ali F , An H , Awe A , Baldwin D , Baden H , Barnstead M , Barrow I , Beeson K , Busam D , Carver A , Center A , Cheng ML , Curry L , Danaher S , Davenport L , Desilets R , Dietz S , Dodson K , Doup L , Ferriera S , Garg N , Gluecksmann A , Hart B , Haynes J , Haynes C , Heiner C , Hladun S , Hostin D , Houck J , Howland T , Ibegwam C , Johnson J , Kalush F , Kline L , Koduru S , Love A , Mann F , May D , McCawley S , McIntosh T , McMullen I , Moy M , Moy L , Murphy B , Nelson K , Pfannkoch C , Pratts E , Puri V , Qureshi H , Reardon M , Rodriguez R , Rogers YH , Romblad D , Ruhfel B , Scott R , Sitter C , Smallwood M , Stewart E , Strong R , Suh E , Thomas R , Tint NN , Tse S , Vech C , Wang G , Wetter J , Williams S , Williams M , Windsor S , Winn-Deen E , Wolfe K , Zaveri J , Zaveri K , Abril JF , Guigo R , Campbell MJ , Sjolander KV , Karlak B , Kejariwal A , Mi H , Lazareva B , Hatton T , Narechania A , Diemer K , Muruganujan A , Guo N , Sato S , Bafna V , Istrail S , Lippert R , Schwartz R , Walenz B , Yooseph S , Allen D , Basu A , Baxendale J , Blick L , Caminha M , Carnes-Stine J , Caulk P , Chiang YH , Coyne M , Dahlke C , Mays A , Dombroski M , Donnelly M , Ely D , Esparham S , Fosler C , Gire H , Glanowski S , Glasser K , Glodek A , Gorokhov M , Graham K , Gropman B , Harris M , Heil J , Henderson S , Hoover J , Jennings D , Jordan C , Jordan J , Kasha J , Kagan L , Kraft C , Levitsky A , Lewis M , Liu X , Lopez J , Ma D , Majoros W , McDaniel J , Murphy S , Newman M , Nguyen T , Nguyen N , Nodell M , Pan S , Peck J , Peterson M , Rowe W , Sanders R , Scott J , Simpson M , Smith T , Sprague A , Stockwell T , Turner R , Venter E , Wang M , Wen M , Wu D , Wu M , Xia A , Zandieh A , Zhu X
Ref : Science , 291 :1304 , 2001
Abstract : A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.
ESTHER : Venter_2001_Science_291_1304
PubMedSearch : Venter_2001_Science_291_1304
PubMedID: 11181995
Gene_locus related to this paper: human-AADAC , human-ABHD1 , human-ABHD10 , human-ABHD11 , human-ACHE , human-BCHE , human-LDAH , human-ABHD18 , human-CMBL , human-ABHD17A , human-KANSL3 , human-LIPA , human-LYPLAL1 , human-NDRG2 , human-NLGN3 , human-NLGN4X , human-NLGN4Y , human-PAFAH2 , human-PREPL , human-RBBP9 , human-SPG21

Title : The chemokine interleukin-8 acutely reduces Ca(2+) currents in identified cholinergic septal neurons expressing CXCR1 and CXCR2 receptor mRNAs - Puma_2001_J.Neurochem_78_960
Author(s) : Puma C , Danik M , Quirion R , Ramon F , Williams S
Ref : Journal of Neurochemistry , 78 :960 , 2001
Abstract : The chemokine IL-8 is known to be synthesized by glial cells in the brain. It has traditionally been shown to have an important role in neuroinflammation but recent evidence indicates that it may also be involved in rapid signaling in neurons. We investigated how IL-8 participates in rapid neuronal signaling by using a combination of whole-cell recording and single-cell RT-PCR on dissociated rat septal neurons. We show that IL-8 can acutely reduce Ca(2+) currents in septal neurons, an effect that was concentration-dependent, involved the closure of L- and N-type Ca(2+) channels, and the activation of G(ialpha1) and/or G(ialpha2) subtype(s) of G-proteins. Analysis of the mRNAs from the recorded neurons revealed that the latter were all cholinergic in nature. Moreover, we found that all cholinergic neurons that responded to IL-8, expressed mRNAs for either one or both IL-8 receptors CXCR1 and CXCR2. This is the first report of a chemokine that modulates ion channels in neurons via G-proteins, and the first demonstration that mRNAs for CXCR1 are expressed in the brain. Our results suggest that IL-8 release by glial cells in vivo may activate CXCR1 and CXCR2 receptors on cholinergic septal neurons and acutely modulate their excitability by closing calcium channels.
ESTHER : Puma_2001_J.Neurochem_78_960
PubMedSearch : Puma_2001_J.Neurochem_78_960
PubMedID: 11553670

Title : GABAergic input to cholinergic nucleus basalis neurons - Khateb_1998_Neurosci_86_937
Author(s) : Khateb A , Fort P , Williams S , Serafin M , Muhlethaler M , Jones BE
Ref : Neuroscience , 86 :937 , 1998
Abstract : The potential influence of GABAergic input to cholinergic basalis neurons was studied in guinea-pig basal forebrain slices. GABA and its agonists were applied to electrophysiologically-identified cholinergic neurons, of which some were labelled with biocytin and confirmed to be choline acetyltransferase-immunoreactive. Immunohistochemistry for glutamate decarboxylase was also performed in some slices and revealed GABAergic varicosities in the vicinity of the biocytin-filled soma and dendrites of electrophysiologically-identified cholinergic cells. From rest (average - 63 mV), the cholinergic cells were depolarized by GABA. The depolarization was associated with a decrease in membrane resistance and diminution in firing. The effect was mimicked by muscimol, the specific agonist for GABA(A) receptors, and not by baclofen, the specific agonist for GABA(B) receptors, which had no discernible effect. The GABA- and muscimol-evoked depolarization and decrease in resistance were found to be postsynaptic since they persisted in the presence of solutions containing either high Mg2+/low Ca2+ or tetrodotoxin. They were confirmed as being mediated by a GABA(A) receptor, since they were antagonized by bicuculline. The reversal potential for the muscimol effect was estimated to be approximately -45 mV, which was -15 mV above the resting membrane potential. Finally, in some cholinergic cells, spontaneous subthreshold depolarizing synaptic potentials (average 5 mV in amplitude), which were rarely associated with action potentials, were recorded and found to persist in the presence of glutamate receptor antagonists but to be eliminated by bicuculline. These results suggest that GABAergic input may be depolarizing, yet predominantly inhibitory to cholinergic basalis neurons.
ESTHER : Khateb_1998_Neurosci_86_937
PubMedSearch : Khateb_1998_Neurosci_86_937
PubMedID: 9692729

Title : Modulation of cholinergic nucleus basalis neurons by acetylcholine and N-methyl-D-aspartate - Khateb_1997_Neurosci_81_47
Author(s) : Khateb A , Fort P , Williams S , Serafin M , Jones BE , Muhlethaler M
Ref : Neuroscience , 81 :47 , 1997
Abstract : Known to exert an important modulatory influence on the cerebral cortex, the cholinergic neurons of the basal forebrain are modulated in turn by neurotransmitters which may include acetylcholine released from processes of brainstem or forebrain neurons. In the present study, we examined the effect of carbachol, a non-specific cholinergic agonist, either alone or in the presence of N-methyl-D-aspartate upon electrophysiologically identified cholinergic basalis neurons in guinea-pig basal forebrain slices. Carbachol produced a direct postsynaptic hyperpolarization, accompanied by a decrease in membrane resistance. Muscarine could mimic this hyperpolarizing effect, whereas nicotine produced a direct postsynaptic membrane depolarization. The interaction of carbachol with N-methyl-D-aspartate was subsequently tested since, in a prior study, N-methyl-D-aspartate was shown to induce rhythmic bursting in cholinergic cells when they were hyperpolarized by continuous injection of outward current. Applied simultaneously with N-methyl-D-aspartate in the absence of current injection, carbachol was also found to promote rhythmic bursting in half of the cells tested. Since the bursts under these conditions were markedly longer in duration than those observed in the presence of N-methyl-D-aspartate alone, it was hypothesized that carbachol might have another action, in addition to the membrane hyperpolarization. Using dissociated cells, it was found that brief applications of carbachol could indeed diminish the slow afterhyperpolarizations that follow single spikes, short bursts or long trains of action potentials in cholinergic basalis neurons. These results indicate that, through its dual ability to hyperpolarize cholinergic neurons and to reduce their afterhyperpolarizations, acetylcholine can promote the occurrence of rhythmic bursting in the presence of N-methyl-D-aspartate. Accordingly, whether derived from brainstem or local sources, acetylcholine may facilitate rhythmic discharge in cholinergic basalis neurons which could in turn impose a rhythmic modulation upon cortical activity during particular states across the sleep-waking cycle.
ESTHER : Khateb_1997_Neurosci_81_47
PubMedSearch : Khateb_1997_Neurosci_81_47
PubMedID: 9300400