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1.
Sci Rep ; 9(1): 9506, 2019 Jun 26.
Article in English | MEDLINE | ID: mdl-31239448

ABSTRACT

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.

2.
Sci Rep ; 8(1): 8963, 2018 06 12.
Article in English | MEDLINE | ID: mdl-29895973

ABSTRACT

The stellate ganglia are the predominant source of sympathetic innervation to the heart. Remodeling of the nerves projecting to the heart has been observed in several cardiovascular diseases, however studies of adult stellate ganglia are limited. A profile of the baseline transcriptomic and neurochemical characteristics of the stellate ganglia in adult C57Bl6j mice, a common model for the study of cardiovascular diseases, may aid future investigations. We have generated a dataset of baseline measurements of mouse stellate ganglia using RNAseq, HPLC and mass spectrometry. Expression differences between male and female mice were identified. These differences included physiologically important genes for growth factors, receptors and ion channels. While the neurochemical profiles of male and female stellate ganglia were not different, minor differences in neurotransmitter content were identified in heart tissue.


Subject(s)
Gene Expression Profiling , Gene Expression Regulation/physiology , Sex Characteristics , Stellate Ganglion/metabolism , Animals , Brain Chemistry/physiology , Female , Male , Mice , Stellate Ganglion/cytology
3.
Mol Psychiatry ; 22(1): 134-141, 2017 01.
Article in English | MEDLINE | ID: mdl-27046647

ABSTRACT

Norepinephrine released from sympathetic nerves is removed from the neuroeffector junction via the action of the norepinephrine transporter (NET). NET impairment is evident in several clinically important conditions including major depressive disorder (MDD), panic disorder (PD), essential hypertension and the postural orthostatic tachycardia syndrome (POTS). We aimed to determine whether a single nucleotide polymorphism (SNP) in the 3' untranslated region (UTR) of the NET gene is associated with NET impairment and to elucidate the mechanisms involved. The analyses were carried out in two cohorts of European ancestry, which included healthy controls and MDD, PD, hypertensive and POTS patients. Compared with controls, cases had significantly higher prevalence of the T allele of rs7194256 (C/T), arterial norepinephrine, depression and anxiety scores, larger left ventricular mass index, higher systolic and diastolic blood pressures, and heart rate. Bioinformatic analysis identified that the microRNA miR-19a-3p could bind preferentially to the sequence created by the presence of the T allele. This was supported by results of luciferase assays. Compared with controls, cases had significantly lower circulating miR-19a-3p, which was associated with pathways related to blood pressure and regulation of neurotransmission. In vitro norepinephrine downregulated miR-19a-3p. In conclusion, the T allele of the rs7194256 SNP in the 3'UTR of the NET gene is more prevalent in diseases where NET impairment is evident. This might be explained by the creation of a binding site for the microRNA miR-19a-3p. A defect in NET function may potentiate the sympathetic neurochemical signal, predisposing individuals with affective diseases to increased risk of cardiovascular disease development.


Subject(s)
Norepinephrine Plasma Membrane Transport Proteins/genetics , 3' Untranslated Regions/genetics , Adult , Alleles , Binding Sites , Cardiovascular Diseases , Cohort Studies , Computational Biology , Depressive Disorder, Major/genetics , Essential Hypertension , Female , Heart Rate , Humans , Hypertension/genetics , Male , MicroRNAs/genetics , Middle Aged , Norepinephrine/metabolism , Norepinephrine Plasma Membrane Transport Proteins/metabolism , Panic Disorder/genetics , Polymorphism, Single Nucleotide/genetics , Postural Orthostatic Tachycardia Syndrome/genetics , White People/genetics
4.
Theor Appl Genet ; 118(4): 695-702, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19034409

ABSTRACT

Fusarium head blight (FHB) is an important disease of wheat worldwide. Soissons is one of the most resistant varieties grown in UK. The current study was undertaken to identify QTL for FHB resistance in Soissons and to determine whether the semi-dwarfing alleles Rht-B1b and Rht-D1b have a similar influence on susceptibility to FHB. A Soissons (Rht-B1b; Rht-D1a) x Orvantis (Rht-B1a; Rht-D1b) doubled haploid (DH) population was assessed for FHB resistance in three trials. Soissons contributed a single, stable major FHB QTL linked to the Rht-D1 locus. In contrast, the Rht-B1b allele (contributed by Soissons) conferred no negative effect on FHB resistance, even conferring a very minor positive effect in one trial. The influence of the Rht-B1b and Rht-D1b alleles on FHB resistance was further investigated using both Mercia and Maris Huntsman near-isogenic lines. Under high disease pressure both Rht-B1b and Rht-D1b significantly decreased Type 1 resistance (resistance to initial infection). However, whilst Rht-D1b has no effect on Type 2 resistance (resistance to spread of the fungus within the spike), Rht-B1b significantly increased Type 2 resistance. Our study demonstrates that the choice of semi-dwarfing gene used in plant breeding programmes may be a significant consideration where resistance to FHB is an important breeding target.


Subject(s)
Immunity, Innate/genetics , Plant Diseases/microbiology , Plant Proteins/genetics , Quantitative Trait Loci/genetics , Triticum/genetics , Analysis of Variance , Chromosome Mapping , Crosses, Genetic , DNA Primers/genetics , Fusarium , Genotype , Plant Diseases/genetics , Triticum/growth & development
5.
Infect Immun ; 68(10): 5546-51, 2000 Oct.
Article in English | MEDLINE | ID: mdl-10992452

ABSTRACT

Recombinant beta-toxin from Clostridium perfringens type C was found to increase the conductance of bilayer lipid membranes (BLMs) by inducing channel activity. The channels exhibited a distribution of conductances within the range of 10 to 380 pS, with the majority of the channels falling into two categories of conductance at 110 and 60 pS. The radii of beta-toxin pores found for the conductance states of 110 and 60 pS were 12.7 and 11.1 A, respectively. The single channels and the steady-state currents induced by beta-toxin across the BLMs exhibited ideal monovalent cation selectivity. Addition of divalent cations (Zn(2+), Cd(2+), or Mg(2+)) at a concentration of 2 mM increased the rate of beta-toxin insertion into BLMs and the single-channel conductance, while application of 5 mM Zn(2+) to a beta-toxin-induced steady-state current decreased the inward current by approximately 45%. The mutation of arginine 212 of beta-toxin to aspartate, previously shown to increase the 50% lethal dose of beta-toxin for mice nearly 13-fold, significantly reduced the ability of beta-toxin to form channels. These data support the hypothesis that the lethal action of beta-toxin is based on the formation of cation-selective pores in susceptible cells.


Subject(s)
Bacterial Toxins/toxicity , Clostridium perfringens/pathogenicity , Ion Channels/metabolism , Lipid Bilayers/metabolism , Animals , Bacterial Toxins/genetics , Cations/metabolism , Clostridium Infections/microbiology , Clostridium perfringens/metabolism , Female , Membrane Potentials , Mice , Recombinant Fusion Proteins/toxicity , Swine
6.
Biol Psychol ; 30(1): 21-33, 1990 Feb.
Article in English | MEDLINE | ID: mdl-2223933

ABSTRACT

Attention-related changes in the human auditory brainstem response and the short-latency somatosensory evoked potential (SLSEP) were demonstrated in separate experiments. In Experiment 1, ABRs were recorded during conditions in which subjects awaited the presentation of either auditory or somatosensory target stimuli. In Experiment 2, median nerve SLSEPs were recorded in a similar task context. Analyses of ABR and SLSEP component amplitudes and latencies revealed that the auditory nerve (wave II) and rostral brainstem (wave V) components of the ABR, and the cervical component (N12) of the SLSEP, were facilitated when attention was directed toward stimuli that were presented in the same sensory modality and receptive field as the EP-eliciting stimuli. These results suggest that central mechanisms can modulate the transmission of auditory and somatosensory information at an early, precortical stage and that these mechanisms play a role in auditory and somatosensory selective attention.


Subject(s)
Arousal/physiology , Attention/physiology , Auditory Perception/physiology , Cerebral Cortex/physiology , Electroencephalography , Sensation/physiology , Adult , Evoked Potentials, Auditory, Brain Stem/physiology , Evoked Potentials, Somatosensory/physiology , Humans , Male
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