595 research outputs found

    Spindle oscillations are generated in the dorsal thalamus and modulated by the thalamic reticular nucleus

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    Spindle waves occur during the early stage of slow wave sleep and are thought to arise in the thalamic reticular nucleus (TRN), causing inhibitory postsynaptic potential spindle-like oscillations in the dorsal thalamus that are propagated to the cortex. We have found that thalamocortical neurons exhibit membrane oscillations that have spindle frequencies, consist of excitatory postsynaptic potentials, and co-occur with electroencephalographic spindles. TRN lesioning prolonged oscillations in the medial geniculate body (MGB) and auditory cortex (AC). Injection of GABA~A~ antagonist into the MGB decreased oscillation frequency, while injection of GABA~B~ antagonist increased spindle oscillations in the MGB and cortex. Thus, spindles originate in the dorsal thalamus and TRN inhibitory inputs modulate this process, with fast inhibition facilitating the internal frequency and slow inhibition limiting spindle occurrence

    Correlation between the cystathionine-r-lyase (CES) and the severity of peptic ulcer disease

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    Background: The infection of Helicobacter pylori (H. pylori) is one of the most important causes of gastric ulcer disease. The role of hydrogen sulfide (H2S) production in H. pylori-induced gastric ulcer disease. Aim: The expression of cystathionine-γ-lyase (CSE) was determined, and correlated with the severity of gastric ulcer disease. Methods: 108 patients were selected based on the determination of gastric ulcer and the infection of Helicobacter pylori (H. pylori), including 36 normal control, 36 patients with H. Pylori-negative gastric ulcer, and 36 patients with H. Pylori-positive gastric ulcer. RT-PCR determination was performed to determine the expression of CSE, NF-κB and IL-8. Results: The expression of CSE, NF-κB and IL-8 was higher in gastric ulcer group than control group (p < 0.05). Compared with the H.pylori-negative gastric ulcer, the expression of CSE, NF-κB and IL-8 was higher than H.pylori-positive gastric ulcer group (p < 0.05). For H.pylori-negative gastric ulcer group, the expression of CSE positively correlated with the expression of NF-κB (r=0.98, p < 0.05) and IL-8 (r=0.95, p 0.05). For H.pylori-positive gastric ulcer group, the expression of CSE also positively correlated with the expression of NF-κB (r=0.99, p < 0.05) and IL-8 (r=0.85, p < 0.05). Conclusion: The expression of CSE was positively correlated with the severity of gastric ulcer.Keywords: Helicobacter pylori (H. pylori), gastric ulcer, hydrogen sulfide (H2S), cystathionine-γ-lyase (CSE)African Health sciences Vol 14 No. 1 March 201

    How tyramine β-hydroxylase controls the production of octopamine, modulating the mobility of beetles

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    Biogenic amines perform many kinds of important physiological functions in the central nervous system (CNS) of insects, acting as neuromodulators, neurotransmitters, and neurohormones. The five most abundant types of biogenic amines in invertebrates are dopamine, histamine, serotonin, tyramine, and octopamine (OA). However, in beetles, an important group of model and pest insects, the role of tyramine beta-hydroxylase (T beta H) in the OA biosynthesis pathway and the regulation of behavior remains unknown so far. We therefore investigated the molecular characterization and spatiotemporal expression profiles of T beta H in red flour beetles (Triboliun castaneum). Most importantly, we detected the production of OA and measured the crawling speed of beetles after dsTcT beta H injection. We concluded that TcT beta H controls the biosynthesis amount of OA in the CNS, and this in turn modulates the mobility of the beetles. Our new results provided basic information about the key genes in the OA biosynthesis pathway of the beetles, and expanded our knowledge on the physiological functions of OA in insects

    mGluR5 antagonism inhibits cocaine reinforcement and relapse by elevation of extracellular glutamate in the nucleus accumbens via a CB1 receptor mechanism.

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    Metabotropic glutamate receptor 5 (mGluR5) antagonism inhibits cocaine self-administration and reinstatement of drug-seeking behavior. However, the cellular and molecular mechanisms underlying this action are poorly understood. Here we report a presynaptic glutamate/cannabinoid mechanism that may underlie this action. Systemic or intra-nucleus accumbens (NAc) administration of the mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) dose-dependently reduced cocaine (and sucrose) self-administration and cocaine-induced reinstatement of drug-seeking behavior. The reduction in cocaine-taking and cocaine-seeking was associated with a reduction in cocaine-enhanced extracellular glutamate, but not cocaine-enhanced extracellular dopamine (DA) in the NAc. MPEP alone, when administered systemically or locally into the NAc, elevated extracellular glutamate, but not DA. Similarly, the cannabinoid CB1 receptor antagonist, rimonabant, elevated NAc glutamate, not DA. mGluR5s were found mainly in striatal medium-spiny neurons, not in astrocytes, and MPEP-enhanced extracellular glutamate was blocked by a NAc CB1 receptor antagonist or N-type Ca++ channel blocker, suggesting that a retrograde endocannabinoid-signaling mechanism underlies MPEP-induced glutamate release. This interpretation was further supported by our findings that genetic deletion of CB1 receptors in CB1-knockout mice blocked both MPEP-enhanced extracellular glutamate and MPEP-induced reductions in cocaine self-administration. Together, these results indicate that the therapeutic anti-cocaine effects of mGluR5 antagonists are mediated by elevation of extracellular glutamate in the NAc via an endocannabinoid-CB1 receptor disinhibition mechanism

    PIH1D3-knockout rats exhibit full ciliopathy features and dysfunctional pre-assembly and loading of dynein arms in motile cilia

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    Background: Recessive mutation of the X-linked gene, PIH1 domain-containing protein 3 (PIH1D3), causes familial ciliopathy. PIH1D3 deficiency is associated with the defects of dynein arms in cilia, but how PIH1D3 specifically affects the structure and function of dynein arms is not understood yet. To gain insights into the underlying mechanisms of the disease, it is crucial to create a reliable animal model. In humans, rats, and mice, one copy of the PIH1D3 gene is located on the X chromosome. Interestingly, mice have an additional, intronless copy of the Pih1d3 gene on chromosome 1. To develop an accurate disease model, it is best to manipulate the X-linked PIH1D3 gene, which contains essential regulatory sequences within the introns for precise gene expression. This study aimed to develop a tailored rat model for PIH1D3-associated ciliopathy with the ultimate goal of uncovering the intricate molecular mechanisms responsible for ciliary defects in the disease.Methods: Novel Pih1d3-knockout (KO) rats were created by using TALEN-mediated non-homologous DNA recombination within fertilized rat eggs and, subsequently, underwent a comprehensive characterization through a battery of behavioral and pathological assays. A series of biochemical and histological analyses were conducted to elucidate the identity of protein partners that interact with PIH1D3, thus shedding light on the intricate molecular mechanisms involved in this context.Results: PIH1D3-KO rats reproduced the cardinal features of ciliopathy including situs inversus, defects in spermatocyte survival and mucociliary clearance, and perinatal hydrocephalus. We revealed the novel function of PIH1D3 in cerebrospinal fluid circulation and elucidated the mechanism by which PIH1D3 deficiency caused communicating hydrocephalus. PIH1D3 interacted with the proteins required for the pre-assembly and uploading of outer (ODA) and inner dynein arms (IDA), regulating the integrity of dynein arm structure and function in cilia.Conclusion: PIH1D3-KO rats faithfully reproduced the cardinal features of ciliopathy associated with PIH1D3 deficiency. PIH1D3 interacted with the proteins responsible for the pre-assembly and uploading of dynein arms in cilia, and its deficiency led to dysfunctional cilia and, thus, to ciliopathy by affecting the pre-assembly and uploading of dynein arms. The resultant rat model is a valuable tool for the mechanistic study of PIH1D3-caused diseases

    Vertical habitat preferences shape the fish gut microbiota in a shallow lake

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    Understanding the interactions between fish gut microbiota and the aquatic environment is a key issue for understanding aquatic microorganisms. Environmental microorganisms enter fish intestines through feeding, and the amount of invasion varies due to different feeding habits. Traditional fish feeding habitat preferences are determined by fish morphology or behavior. However, little is known about how the feeding behavior of fish relative to the vertical structure in a shallow lake influences gut microbiota. In our study, we used nitrogen isotopes to measure the trophic levels of fish. Then high-throughput sequencing was used to describe the composition of environmental microbiota and fish gut microbiota, and FEAST (fast expectation-maximization for microbial source tracking) method was used to trace the source of fish gut microbiota. We investigated the microbial diversity of fish guts and their habitats in Lake Sanjiao and verified that the sediments indeed played an important role in the assembly of fish gut microbiota. Then, the FEAST analysis indicated that microbiota in water and sediments acted as the primary sources in half of the fish gut microbiota respectively. Furthermore, we classified the vertical habitat preferences using microbial data and significant differences in both composition and function of fish gut microbiota were observed between groups with distinct habitat preferences. The performance of supervised and unsupervised machine learning in classifying fish gut microbiota by habitat preferences actually exceeded classification by fish species taxonomy and fish trophic level. Finally, we described the stability of fish co-occurrence networks with different habitat preferences. Interestingly, the co-occurrence network seemed more stable in pelagic fish than in benthic fish. Our results show that the preferences of fish in the vertical structure of habitat was the main factor affecting their gut microbiota. We advocated the use of microbial interactions between fish gut and their surrounding environment to reflect fish preferences in vertical habitat structure. This approach not only offers a novel perspective for understanding the interactions between fish gut microbiota and environmental factors, but also provides new methods and ideas for studying fish habitat selection in aquatic ecosystems

    Surface characterization, mechanical properties and corrosion behaviour of ternary based ZneZnOeSiO2composite coating of mild steel

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    Zinc coatings are obtained either from cyanide, non-cyanide alkaline or acid solutions. Because of the pollution and high cost associated with cyanide, deposition from other baths is gaining importance. In order to develop a bath with additive that could produce a quality coating is the motivation behind this present work which is surface modification of Zne8ZnOeSiO2 nano composite coating on mild steel surface by electrodeposition route. The influence of SiO2 on Zne8ZnO sulphate electrolyte on the properties and microstructure of the produced nano-coatings were investigated. The SiO2 was varied from 0 to 16wt%. The microstructure characteristics of these produced series composites coating were investigated using scanning electron microscopy couple with energy dispersive spectroscopy (SEM/EDS), X-ray diffraction and atomic force microscopy (AFM). The corrosion degradation properties in 3.65% NaCl medium were studied using potentiodynamic polarization technique and characterized by high resolution optical microscope (HR-OPM). The hardness and wear of the composite coating were measured with high diamond microhardness tester and dry abrasive MTR-300 testers respectively. The results showed that average hardness value of 142.5 and 251.2HV and corrosion rate of 0.13088 and 0.00122 mm/yr were obtained for the 0 and 16wt% SiO2 in Zne8ZnO. The work have established that upto 16% SiO2 in Zne8ZnO composite coating on mild steel can be used in improving the microhardness, wear loss and corrosion resistance of mild stee

    A study of clinical and serological correlation of early myocardial injury in elderly patients infected with the Omicron variant

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    IntroductionMyocardial injury in elderly Omicron variant patients is a leading cause of severe disease and death. This study focuses on elucidating the clinical characteristics and potential risk factors associated with myocardial injury in elderly patients infected with the Omicron variant.MethodsMyocardial injury was defined based on elevated cardiac troponin concentrations exceeding the 99th percentile upper reference limit. Among 772 elderly Omicron-infected patients, categorized into myocardial injury (n = 263) and non-myocardial injury (n = 509) groups. The stratified log-rank statistic was used to compare the probability of patients developing intensive care. Receiver operating characteristic curves were used to determine the best cut-off values of clinical and laboratory data for predicting myocardial injury. Univariate and multivariate logistic regression was adopted to analyze the risk factors for myocardial injury.ResultsThe occurrence of myocardial injury in Omicron variant-infected geriatric patients was up to 34.07% and these patients may have a higher rate of requiring intensive care (P < 0.05). By comparing myocardial injury patients with non-myocardial injury patients, notable differences were observed in age, pre-existing medical conditions (e.g., hypertension, coronary heart disease, cerebrovascular disease, arrhythmia, chronic kidney disease, and heart failure), and various laboratory biomarkers, including cycle threshold-ORF1ab gene (Ct-ORF1ab), cycle threshold-N gene (Ct-N), white blood cell count, neutrophil (NEUT) count, NEUT%, lymphocyte (LYM) count, LYM%, and D-dimer, interleukin-6, procalcitonin, C-reactive protein, serum amyloid A, total protein, lactate dehydrogenase, aspartate aminotransferase, glomerular filtration rate, blood urea nitrogen, and serum creatinine (sCr) levels (P < 0.05). Furthermore, in the multivariable logistic regression, we identified potential risk factors for myocardial injury in Omicron variant–infected elderly patients, including advanced age, pre-existing coronary artery disease, interleukin-6 > 22.69 pg/ml, procalcitonin > 0.0435 ng/ml, D-dimer > 0.615 mg/L, and sCr > 81.30 μmol/L.ConclusionThis study revealed the clinical characteristics and potential risk factors associated with myocardial injury that enable early diagnosis of myocardial injury in Omicron variant-infected elderly patients, providing important reference indicators for early diagnosis and timely clinical intervention
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