scholarly journals Functional specification of CCK+ interneurons by alternative isoforms of Kv4.3 auxiliary subunits

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Viktor János Oláh ◽  
David Lukacsovich ◽  
Jochen Winterer ◽  
Antónia Arszovszki ◽  
Andrea Lőrincz ◽  
...  
Keyword(s):  
Low Voltage ◽  
Auxiliary Subunits ◽  
Functional Specification ◽  
Gene Profiles ◽  
Hippocampal Activity ◽  
Hippocampal Ca3 ◽  
Underlying Mechanisms ◽  
Firing Properties ◽  
A Minor ◽  
Whole Transcriptome

CCK-expressing interneurons (CCK+INs) are crucial for controlling hippocampal activity. We found two firing phenotypes of CCK+INs in rat hippocampal CA3 area; either possessing a previously undetected membrane potential-dependent firing or regular firing phenotype, due to different low-voltage-activated potassium currents. These different excitability properties destine the two types for distinct functions, because the former is essentially silenced during realistic 8–15 Hz oscillations. By contrast, the general intrinsic excitability, morphology and gene-profiles of the two types were surprisingly similar. Even the expression of Kv4.3 channels were comparable, despite evidences showing that Kv4.3-mediated currents underlie the distinct firing properties. Instead, the firing phenotypes were correlated with the presence of distinct isoforms of Kv4 auxiliary subunits (KChIP1 vs. KChIP4e and DPP6S). Our results reveal the underlying mechanisms of two previously unknown types of CCK+INs and demonstrate that alternative splicing of few genes, which may be viewed as a minor change in the cells’ whole transcriptome, can determine cell-type identity.

scholarly journals Functional specification of CCK+ interneurons by alternative isoforms of Kv4.3 auxiliary subunits

2019 ◽  
Author(s):  
Viktor János Oláh ◽  
David Lukacsovich ◽  
Jochen Winterer ◽  
Andrea Lőrincz ◽  
Zoltan Nusser ◽  
...  
Keyword(s):  
Low Voltage ◽  
Distinct Cell Type ◽  
Auxiliary Subunits ◽  
Functional Specification ◽  
Gene Profiles ◽  
Hippocampal Activity ◽  
Distinct Cell ◽  
Underlying Mechanisms ◽  
Firing Properties ◽  
A Minor

AbstractCCK-expressing interneurons (CCK+INs) are crucial for controlling hippocampal activity. We found two firing phenotypes of CCK+INs in rat CA3 area; either possessing a previously undetected membrane potential-dependent firing or regular firing phenotype, due to different low-voltage-activated potassium currents. These different excitability properties destine the two types for distinct functions, because the former is essentially silenced during realistic 8-15 Hz oscillations. The general excitability, morphology and gene-profiles of the two types were surprisingly similar. Even the expression of Kv4.3 channels were comparable, despite evidences showing that Kv4.3-mediated currents underlie the distinct firing properties. Instead, the firing phenotypes were correlated with the presence of distinct isoforms of Kv4 auxiliary subunits (KChIP1 vs. KChIP4e and DPP6S). Our results reveal the underlying mechanisms of two previously unknown types of CCK+INs and demonstrate that alternative splicing of few genes, which may be viewed as a minor event in the cells’ whole transcriptome, can underlie distinct cell-type identity.

RyR1 exhibits lower gain of CICR activity than RyR3 in the SR: evidence for selective stabilization of RyR1 channel

2004 ◽  
Vol 287 (1) ◽  
pp. C36-C45 ◽  
Author(s):  
Takashi Murayama ◽  
Yasuo Ogawa
Keyword(s):  
Binding Sites ◽  
Skeletal Muscles ◽  
Specific Activity ◽  
Adenine Nucleotides ◽  
Minor Effect ◽  
Mammalian Skeletal Muscle ◽  
Selective Stabilization ◽  
Underlying Mechanisms ◽  
A Minor

We showed that frog α-ryanodine receptor (α-RyR) had a lower gain of Ca2+-induced Ca2+ release (CICR) activity than β-RyR in sarcoplasmic reticulum (SR) vesicles, indicating selective “stabilization” of the former isoform (Murayama T and Ogawa Y. J Biol Chem 276: 2953–2960, 2001). To know whether this is also the case with mammalian RyR1, we determined [3H]ryanodine binding of RyR1 and RyR3 in bovine diaphragm SR vesicles. The value of [3H]ryanodine binding (B) was normalized by the number of maximal binding sites (Bmax), whereby the specific activity of each isoform was expressed. This B/Bmax expression demonstrated that ryanodine binding of individual channels for RyR1 was <15% that for RyR3. Responses to Ca2+, Mg2+, adenine nucleotides, and caffeine were not substantially different between in situ and purified isoforms. These results suggest that the gain of CICR activity of RyR1 is markedly lower than that of RyR3 in mammalian skeletal muscle, indicating selective stabilization of RyR1 as is true of frog α-RyR. The stabilization was partly eliminated by FK506 and partly by solubilization of the vesicles with CHAPS, each of which was additive to the other. In contrast, high salt, which greatly enhances [3H]ryanodine binding, caused only a minor effect on the stabilization of RyR1. None of the T-tubule components, coexisting RyR3, or calmodulin was the cause. The CHAPS-sensitive intra- and intermolecular interactions that are common between mammalian and frog skeletal muscles and the isoform-specific inhibition by FKBP12, which is characteristic of mammals, are likely to be the underlying mechanisms.

scholarly journals Penicillium simplicissimum NL-Z1 Induced an Imposed Effect to Promote the Leguminous Plant Growth

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiayao Zhuang ◽  
Chao Liu ◽  
Xiaoxue Wang ◽  
Tongxin Xu ◽  
Hao Yang
Keyword(s):  
Plant Growth ◽  
Rock Slope ◽  
Plant Biomass ◽  
Control Treatment ◽  
Leguminous Plant ◽  
Penicillium Simplicissimum ◽  
Nodule Biomass ◽  
Underlying Mechanisms ◽  
Phosphate Solubilizing ◽  
A Minor

It is found effective for phytoremediation of the guest soil spraying method by adding microbes to promote the growth of arbor leguminous plant on a high and steep rock slope. However, its underlying mechanisms remain elusive. Here, some experiments were conducted to explore the multifunctions of Penicillium simplicissimum NL-Z1 on rock weathering, nodule growth, and beneficial microbial regulation. The results show that P. simplicissimum NL-Z1 significantly increased the release of phosphorus, potassium, calcium, and magnesium from the rock by 226, 29, 24, and 95%, respectively, compared with that of the control. A significant increase of 153% in Indigofera pseudotinctoria Matsum nodule biomass, accompanied by an increase of 37% in the leguminous plant biomass was observed in the P. simplicissimum NL-Z1 treatment than in the control treatment. Interestingly, even though P. simplicissimum NL-Z1 itself became a minor microbial community in the soil, it induced a significant increase in Mortierella, which, as a beneficial microbe, can promote phosphate-solubilizing and plant growth. The results suggest that P. simplicissimum NL-Z1 could induce an imposed effect to promote leguminous plant growth, which may be conducive to the development of the phytoremediation technique for high and steep rock slope. The study provides a novel thought of using the indirect effect of microbes, i.e., promoting other beneficial microbes, to improve soil environment.

scholarly journals SARS-CoV-2 and the Brain: What Do We Know about the Causality of ‘Cognitive COVID?

2021 ◽  
Vol 10 (15) ◽  
pp. 3441
Author(s):  
Hashir Ali Awan ◽  
Mufaddal Najmuddin Diwan ◽  
Alifiya Aamir ◽  
Muneeza Ali ◽  
Massimo Di Giannantonio ◽  
...  
Keyword(s):  
Olfactory Pathway ◽  
Cognitive Sequelae ◽  
Significant Burden ◽  
Inflammatory State ◽  
Underlying Mechanisms ◽  
Acute Changes ◽  
A Minor

The second year of the COVID-19 (coronavirus disease) pandemic has seen the need to identify and assess the long-term consequences of a SARS-CoV-2 infection on an individual’s overall wellbeing, including adequate cognitive functioning. ‘Cognitive COVID’ is an informal term coined to interchangeably refer to acute changes in cognition during COVID-19 and/or cognitive sequelae with various deficits following the infection. These may manifest as altered levels of consciousness, encephalopathy-like symptoms, delirium, and loss of various memory domains. Dysexecutive syndrome is a peculiar manifestation of ‘Cognitive COVID’ as well. In the previous major outbreaks of viruses like SARS-CoV, MERS-CoV and Influenza. There have been attempts to understand the underlying mechanisms describing the causality of similar symptoms following SARS-CoV-2 infection. This review, therefore, is attempting to highlight the current understanding of the various direct and indirect mechanisms, focusing on the role of neurotropism of SARS-CoV-2, the general pro-inflammatory state, and the pandemic-associated psychosocial stressors in the causality of ‘Cognitive COVID.’ Neurotropism is associated with various mechanisms including retrograde neuronal transmission via olfactory pathway, a general hematogenous spread, and the virus using immune cells as vectors. The high amounts of inflammation caused by COVID-19, compounded with potential intubation, are associated with a deleterious effect on the cognition as well. Finally, the pandemic’s unique psychosocial impact has raised alarm due to its possible effect on cognition. Furthermore, with surfacing reports of post-COVID-vaccination cognitive impairments after vaccines containing mRNA encoding for spike glycoprotein of SARS-CoV-2, we hypothesize their causality and ways to mitigate the risk. The potential impact on the quality of life of an individual and the fact that even a minor proportion of COVID-19 cases developing cognitive impairment could be a significant burden on already overwhelmed healthcare systems across the world make it vital to gather further evidence regarding the prevalence, presentation, correlations, and causality of these events and reevaluate our approach to accommodate early identification, management, and rehabilitation of patients exhibiting cognitive symptoms.

Influence of Post-Injection Parameters on Soot Formation and Oxidation in a Common-Rail-Diesel Engine Using Multi-Color-Pyrometry

2012 ◽  
Author(s):  
Christophe Barro ◽  
Frédéric Tschanz ◽  
Peter Obrecht ◽  
Konstantinos Boulouchos
Keyword(s):  
Oxidation Rate ◽  
Time Window ◽  
Soot Formation ◽  
General Rule ◽  
Soot Oxidation ◽  
Lower Amount ◽  
Post Injection ◽  
Heat Addition ◽  
Underlying Mechanisms ◽  
A Minor

The emission trade-off between soot and NOx is an issue of major concern in automotive diesel applications. Measures need to be taken both on the engine and on the aftertreatment sides in order to optimize the engine emissions while maintaining the highest possible efficiency. It is known that post injections have a potential for exhaust soot reduction without any significant influence in the NOx emissions. However, an accurate and general rule of how to parameterize a post injection such that it provides a maximum reduction of soot emissions does not exist. Moreover, the underlying mechanisms are not understood in detail. The experimental investigation presented here provides insight into the fundamental mechanisms of soot formation and reduction due to post injections under different turbulence and reaction kinetic conditions. In parallel to the measurement of soot elementary carbon in the exhaust (using a Photo Acoustic Soot Sensor), the in-cylinder soot formation and oxidation process have been investigated with an Optical Light Probe (OLP). This sensor provides crank angle resolved information about the in-cylinder soot evolution. The experiments confirm conclusions of earlier works that soot reduction due to a post injection is mainly based on two reasons: increased turbulence (from the post injection) during soot oxidation and lower soot formation due to lower amount of fuel in the main combustion at similar load conditions. A third effect of heat addition during the soot oxidation, which was often mentioned in the literature, could not be confirmed. In addition, the experiments show that variations of turbulence (from swirl) and reaction kinetics have a minor influence on the diffusion controlled heat release rate. However, the time phasing of the soot evolution is highly influenced by these variations with only small changes in the peak soot concentration. It is shown that the soot reduction of a post injection depends on the timing. More precisely, the soot reduction capability of a post injection decreases rapidly as soon as its timing is late in the soot oxidation phase. The soot oxidation rate can only be improved by increased turbulence and heat addition from the post injection in a time window before the in-cylinder soot peak occurs. Depending on EGR and swirl level, a maximum dwell time can be defined after which the post injection effect becomes counterproductive with respect to the soot oxidation rate.

scholarly journals Prebiotic Xylo-Oligosaccharides Ameliorate High-Fat-Diet-Induced Hepatic Steatosis in Rats

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3225
Author(s):  
Sanna Lensu ◽  
Raghunath Pariyani ◽  
Elina Mäkinen ◽  
Baoru Yang ◽  
Wisam Saleem ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Alcoholic Fatty Liver ◽  
Branched Chain Fatty Acids ◽  
Hepatic Fat ◽  
Branched Chain ◽  
Underlying Mechanisms ◽  
A Minor ◽  
Alcoholic Fatty Liver Disease

Understanding the importance of the gut microbiota (GM) in non-alcoholic fatty liver disease (NAFLD) has raised the hope for therapeutic microbes. We have shown that high hepatic fat content associated with low abundance of Faecalibacterium prausnitzii in humans and, further, the administration of F. prausnitzii prevented NAFLD in mice. Here, we aimed at targeting F. prausnitzii by prebiotic xylo-oligosaccharides (XOS) to treat NAFLD. First, the effect of XOS on F. prausnitzii growth was assessed in vitro. Then, XOS was supplemented or not with high (HFD, 60% of energy from fat) or low (LFD) fat diet for 12 weeks in Wistar rats (n = 10/group). XOS increased F. prausnitzii growth, having only a minor impact on the GM composition. When supplemented with HFD, XOS ameliorated hepatic steatosis. The underlying mechanisms involved enhanced hepatic β-oxidation and mitochondrial respiration. Nuclear magnetic resonance (1H-NMR) analysis of cecal metabolites showed that, compared to the HFD, the LFD group had a healthier cecal short-chain fatty acid profile and on the HFD, XOS reduced cecal isovalerate and tyrosine, metabolites previously linked to NAFLD. Cecal branched-chain fatty acids associated positively and butyrate negatively with hepatic triglycerides. In conclusion, XOS supplementation can ameliorate NAFLD by improving hepatic oxidative metabolism and affecting GM.

RNA Profiling of Neuropathic Pain-Associated Human DRGs Reveal Sex-differences in Neuro-immune Interactions Promoting Pain

2021 ◽  
Author(s):  
Pradipta Ray ◽  
Stephanie Shiers ◽  
Diana Tavares Ferreira ◽  
Ishwarya Sankaranarayanan ◽  
Megan L Uhelski ◽  
...  
Keyword(s):  
Sex Differences ◽  
Neuropathic Pain ◽  
Signaling Pathways ◽  
Expression Profiles ◽  
Cytokine Signaling ◽  
Protein Coding ◽  
Rna Profiling ◽  
Cellular Expression ◽  
Underlying Mechanisms ◽  
Whole Transcriptome

Neuropathic pain is a leading cause of high impact pain, is often disabling and is poorly managed by current therapeutics. Here we focused on a unique group of neuropathic pain patients undergoing thoracic vertebrectomy where the DRG is removed as part of the surgery allowing for molecular characterization and identification of mechanistic drivers of neuropathic pain independently of preclinical models. Our goal was to quantify whole transcriptome RNA abundances using RNA-seq in pain-associated human DRGs from these patients, allowing comprehensive identification of molecular changes in these samples by contrasting them with non-pain associated DRGs. We sequenced 70 human DRGs, including over 50 having mRNA libraries with neuronal mRNA. Our expression analysis revealed profound sex differences in differentially expressed genes including increase of IL1B, TNF, CXCL14, and OSM in male and including CCL1, CCL21, PENK and TLR3 in female DRGs associated with neuropathic pain. Co-expression modules revealed enrichment in members of JUN-FOS signaling in males, and centromere protein coding genes in females. Neuro-immune signaling pathways revealed distinct cytokine signaling pathways associated with neuropathic pain in males (OSM, LIF, SOCS1) and females (CCL1, CCL19, CCL21). We validated cellular expression profiles of a subset of these findings using RNAscope in situ hybridization. Our findings give direct support for sex differences in underlying mechanisms of neuropathic pain in patient populations.

Neurochemical mechanisms behind gill microcirculatory responses to hypoxia in trout: in vivo microscopy study

1997 ◽  
Vol 272 (2) ◽  
pp. R576-R585 ◽  
Author(s):  
L. Sundin ◽  
G. E. Nilsson
Keyword(s):  
Blood Flow ◽  
Microscopy Study ◽  
Distal Portion ◽  
Additional Treatment ◽  
Systemic Resistance ◽  
In Vivo Microscopy ◽  
Alpha Adrenoceptor ◽  
Underlying Mechanisms ◽  
A Minor

In vivo microscopy combined with systemic blood flow and pressure measurements were used to examine the hemodynamic and microcirculatory responses to hypoxia in gills of rainbow trout and to clarify if the underlying mechanisms are adrenergic, cholinergic, serotonergic, or adenosinergic. Hypoxia (P(O2) 1.07-1.33 kPa) reduced, halted, or reversed the blood flow in the distal portion of the efferent filamental artery (EFA). Simultaneously, a large overflow to the central venous system appeared, allowing a continuous flow through many of the secondary lamellae. No vasoconstriction could be observed in this portion of the filament, showing that a vasoconstriction occurred elsewhere, possibly at the EFA sphincter, because the gill resistance (R(G)) increased. These effects were mimicked by prebranchial injection of acetylcholine, a treatment that also strongly constricted the distal efferent filamental vasculature. Atropine blocked most of the hypoxia-induced hemodynamic changes, although a minor increase in R(G) remained. The latter appeared to be of a nonadrenergic noncholinergic origin, being unaffected by additional treatment with an alpha-adrenoreceptor antagonist. It was also unaffected by blockers of serotonin and adenosine-A1 receptors. Other responses seen included a cholinergic maintenance of the systemic resistance during hypoxia and an alpha-adrenoceptor-mediated posthypoxic hypertension. This study demonstrates that hypoxia evoked a cholinergic reflex vasoconstriction located at proximal parts of the efferent filamental vasculature.

scholarly journals Delayed functional therapy after acute lateral ankle sprain increases subjective ankle instability – the later, the worse: a retrospective analysis

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Christian Raeder ◽  
Janina Tennler ◽  
Arthur Praetorius ◽  
Tobias Ohmann ◽  
Christian Schoepp
Keyword(s):  
Ankle Sprain ◽  
Ankle Instability ◽  
Diagnostic Code ◽  
Functional Therapy ◽  
International Consensus ◽  
Lateral Ankle Sprain ◽  
Lateral Ankle ◽  
Underlying Mechanisms ◽  
A Minor ◽  
Ankle Function

Abstract Background The lateral ankle sprain (LAS) is one of the most common injuries in everyday and sports activities. Approximately 20–40 % of patients with LAS develop a chronic ankle instability (CAI). The underlying mechanisms for CAI have not yet been clearly clarified. An inadequate rehabilitation after LAS can be speculated, since the LAS is often handled as a minor injury demanding less treatment. Therefore, the aims of this retrospective study were to determine the CAI rate depending on age and sex and to identify possible determinants for developing CAI. Methods Between 2015 and 2018 we applied the diagnostic code “sprain of ankle” (ICD S93.4) to identify relevant cases from the database of the BG Klinikum Duisburg, Germany. Patients received a questionnaire containing the Tegner-Score, the Cumberland Ankle Instability Tool (CAIT) and the Foot and Ankle Disability Index. Additionally, there were questions about the modality and beginning of therapy following LAS and the number of recurrent sprains. There was a total of 647 completed datasets. These were divided into a CAI and non-CAI group according to a CAIT cut-off-score with CAI ≤ 24 and non-CAI > 24 points, representing one out of three criteria for having CAI based on international consensus. Results The overall CAI rate was 17.3 %. We identified a higher CAI rate in females and within the age segment of 41 to 55 years. A later start of therapy (> 4 weeks) after acute LAS significantly increases ankle instability in CAIT (p < .05). There was a significantly higher CAIT score in patients having no recurrent sprain compared to patients having 1–3 recurrent sprains or 4–5 recurrent sprains (p < .001). Conclusions Females over 41 years show a higher CAI rate which implies to perform specific prevention programs improving ankle function following acute LAS. A delayed start of therapy seems to be an important determinant associated with the development of CAI. Another contributing factor may be a frequent number of recurrent sprains that are also linked to greater levels of subjective ankle instability. Therefore, we would recommend an early start of functional therapy after acute LAS in the future to minimize the development of CAI.

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