Find research datasets worth reusing

Data from: Diflunisal inhibits prestin by chloride-dependent mechanism

The motor protein prestin is a member of the SLC26 family of anion antiporters and is essential to the electromotility of cochlear outer hair cells and for hearing. The only direct inhibitor of electromotility and the associated charge transfer is salicylate, possibly through direct interaction with an anion-binding site on prestin. In a screen to identify other inhibitors of prestin activity, we explored the effect of the non-steroid anti-inflammatory drug diflunisal, which is a derivative of salicylate. We recorded prestin activity by whole-cell patch clamping HEK cells transiently expressing prestin and mouse outer hair cells. We monitored the impact of diflunisal on the prestin-dependent non-linear capacitance and electromotility. We found that diflunisal triggers two prestin-associated effects: a chloride independent increase in the surface area and the specific capacitance of the membrane, and a chloride dependent inhibition of the charge transfer and the electromotility in outer hair cells. We conclude that diflunisal affects the cell membrane organization and inhibits prestin-associated charge transfer and electromotility at physiological chloride concentrations. The inhibitory effects on hair cell function are noteworthy given the proposed use of diflunisal to treat neurodegenerative diseases.

opencc-zeroDec 2014View details →

Data from: Effect of lysyl oxidase inhibition on angiotensin II-induced arterial hypertension, remodeling, and stiffness

It is well accepted that angiotensin II (Ang II) induces altered vascular stiffness through responses including both structural and material remodeling. Concurrent with remodeling is the induction of the enzyme lysyl oxidase (LOX) through which ECM proteins are cross-linked. The study objective was to determine the effect of LOX mediated cross-linking on vascular mechanical properties. Three-month old mice were chronically treated with Ang II with or without the LOX blocker, β -aminopropionitrile (BAPN), for 14 days. Pulse wave velocity (PWV) from Doppler measurements of the aortic flow wave was used to quantify in vivo vascular stiffness in terms of an effective Young's modulus. The increase in effective Young's modulus with Ang II administration was abolished with the addition of BAPN, suggesting that the material properties are a major controlling element in vascular stiffness. BAPN inhibited the Ang II induced collagen cross-link formation by 2-fold and PWV by 44% (P<0.05). Consistent with this observation, morphometric analysis showed that BAPN did not affect the Ang II mediated increase in medial thickness but significantly reduced the adventitial thickness. Since the hypertensive state contributes to the measured in vivo PWV stiffness, we removed the Ang II infusion pumps on Day 14 and achieved normal arterial blood pressures. With pump removal we observed a decrease of the PWV in the Ang II group to 25% above that of the control values (P=0.002), with a complete return to control values in the Ang II plus BAPN group. In conclusion, we have shown that the increase in vascular stiffness with 14 day Ang II administration results from a combination of hypertension-induced wall strain, adventitial wall thickening and Ang II mediated LOX ECM cross-linking, which is a major material source of vascular stiffening, and that the increased PWV was significantly inhibited with co-administration of BAPN.

opencc-zeroDec 2017View details →

Data from: Early modulation of intra-cortical inhibition during the observation of action mistakes

Errors while performing an action are fundamental for learning. During interaction others' errors must be monitored and taken into account to allow joint action coordination and imitation learning. This monitoring relies on an action observation network (AON) mainly based on parietofrontal recurrent circuits. Although different studies suggest that inappropriate actions may rapidly be inhibited during execution, little is known about the modulation of the AON when an action misstep is shown. Here we used single and paired pulse transcranial magnetic stimulation to assess corticospinal excitability, intracortical facilitation and intracortical inhibition at different time intervals (120, 180, 240 ms) after the visual presentation of a motor execution error. Results show a specific and early (120 ms) decrease of intracortical inhibition likely because of a significant mismatch between the observed erroneous action and observer's expectations. Indeed, as proposed by the top-down predictive framework, the motor system may be involved in the generation of these error signals and our data show that this mechanism could rely on the early decrease of intracortical inhibition within the corticomotor system.

Data from: Experimental inhibition of a key cellular antioxidant affects vocal communication

1.There is substantial interest of evolutionary ecologists in the proximate mechanisms that modulate vocal communication. In recent times, there has been growing interest in the role of oxidative stress as a mediator of avian song expression. 2.Here we tested whether the experimental inhibition of the synthesis of a key cellular antioxidant (glutathione) reduces song rate metrics of male European starlings (Sturnus vulgaris). We measured the effect of our treatment on total song rate and on its two components, undirected and nest-box oriented song, outside the breeding season. 3.Treated males that did not own a nest-box (subordinate males likely to be of lower quality) suffered increased oxidative stress relative to untreated males, while treated males that owned a nest-box (dominant males likely to be of higher quality) did not. Treated non-owners also reduced their undirected song rate, whereas treated nest-box owners did not suffer any reduction in song rate. 4.Our results revealed that inhibition of a key cellular antioxidant results in decreased vocal communication in a social vertebrate, and that this effect is dependent on its social status (nest-box owner versus non-owner). 5.This work provides support for the hypothesis that acoustic signals may honestly convey information about the individual oxidative status and capacity to regulate the oxidative balance. Our findings raise the possibility of hitherto unexplored impacts of oxidative stress on fitness traits in social species.

Data from: Positive selection inhibits gene mobilization and transfer in soil bacterial communities

Horizontal gene transfer (HGT) between bacterial lineages is a fundamental evolutionary process that accelerates adaptation. Sequence analyses show that conjugative plasmids are principal agents of HGT in natural communities. However, we lack understanding of how the ecology of bacterial communities and their environments affect the dynamics of plasmid-mediated gene mobilization and transfer. Here we show, in simple experimental soil bacterial communities containing a conjugative mercury resistance plasmid, the repeated, independent mobilization of transposon-borne genes from chromosome to plasmid, plasmid to chromosome and, in the absence of mercury selection, interspecific gene transfers from the chromosome of one species to the other via the plasmid. By reducing conjugation, positive selection for plasmid-encoded traits, like mercury resistance, can consequently inhibit HGT. Our results suggest that interspecific plasmid-mediated gene mobilization is most likely to occur in environments where plasmids are infectious, parasitic elements rather than those where plasmids are positively selected, beneficial elements.

opencc-zeroDec 2018View details →

Data from: Precise excitation-inhibition balance controls gain and timing in the hippocampus

Excitation-inhibition (EI) balance controls excitability, dynamic range, and input gating in many brain circuits. Subsets of synaptic input can be selected or 'gated' by precise modulation of finely tuned EI balance, but assessing the granularity of EI balance requires combinatorial analysis of excitatory and inhibitory inputs. Using patterned optogenetic stimulation of mouse hippocampal CA3 neurons, we show that hundreds of unique CA3 input combinations recruit excitation and inhibition with a nearly identical ratio, demonstrating precise EI balance at the hippocampus. Crucially, the delay between excitation and inhibition decreases as excitatory input increases from a few synapses to tens of synapses. This creates a dynamic millisecond-range window for postsynaptic excitation, controlling membrane depolarization amplitude and timing via subthreshold divisive normalization. We suggest that this combination of precise EI balance and dynamic EI delays forms a general mechanism for millisecond-range input gating and subthreshold gain control in feedforward networks.

opencc-zeroDec 2018View details →

Data from: Adsorption and corrosion inhibition behavior of new theophylline-triazole based derivatives for steel in acidic medium

The design and synthesis of a series of theophylline derivatives containing 1,2,3-triazole moieties is presented. The corrosion inhibition activities of these new triazole-theophylline compounds were evaluated by studying the corrosion of API 5L X52 steel in 1 M HCl media. The results showed that an increase in the concentration of the theophylline-triazole derivatives also increases the charge transference resistance (Rct) value, enhancing inhibition efficiency and decreasing the corrosion process. The electrochemical impedance spectroscopy under static conditions studies revealed that the best inhibition efficiencies (~90%) at 50 ppm are presented by the all- substituted compounds. According to the Langmuir isotherm, the compounds 4 and 5 analyzed exhibit physisorption-chemisorption process, with exception of the hydrogen 3, bromo 6 and iodo 7 substituted compound, which exhibit chemisorption process. The corrosion when submerging a steel bar in 1 M HCl was studied using SEM-EDS. This experiment showed that the corrosion process decreases considerably in the presence of 50 ppm of the organic inhibitors. Finally, theoretical study showed a correlation between EHOMO, hardness (η), electrophilicity (W), atomic charge and the inhibition efficiency in which the iodo 7 substituted compound presents the best inhibitor behavior.

Data from: Nucleolar sub-compartments in motion during rRNA synthesis inhibition: contraction of nucleolar condensed chromatin and gathering of fibrillar centers are concomitant

The nucleolus produces the large polycistronic transcript (47S precursor) containing the 18S, 5.8S and 28S rRNA sequences and hosts most of the nuclear steps of pre-rRNA processing. Among numerous components it contains condensed chromatin and active rRNA genes which adopt a more accessible conformation. For this reason, it is a paradigm of chromosome territory organization. Active rRNA genes are clustered within several fibrillar centers (FCs), in which they are maintained in an open configuration by Upstream Binding Factor (UBF) molecules. Here, we used the reproducible reorganization of nucleolar components induced by the inhibition of rRNA synthesis by Actinomycin D (AMD) to address the steps of the spatiotemporal reorganization of FCs and nucleolar condensed chromatin. To reach that goal, we used two complementary approaches: i) time-lapse confocal imaging of cells expressing one or several GFP-tagged proteins (fibrillarin, UBF, histone H2B) and ii) ultrastructural identification of nucleolar components involved in the reorganization. Data obtained by time lapse confocal microscopy were analyzed through detailed 3D imaging. This allowed us to demonstrate that AMD treatment induces no fusion and no change in the relative position of the different nucleoli contained in one nucleus. In contrast, for each nucleolus, we observed step by step gathering and fusion of both FCs and nucleolar condensed chromatin. To analyze the reorganization of FCs and condensed chromatin at a higher resolution, we performed correlative light and electron microscopy electron microscopy (CLEM) imaging of the same cells. We demonstrated that threads of intranucleolar condensed chromatin are localized in a complex 3D network of vacuoles. Upon AMD treatment, these structures coalesce before migrating toward the perinucleolar condensed chromatin, to which they finally fuse. During their migration, FCs, which are all linked to ICC, are pulled by the latter to gather as caps disposed at the periphery of nucleoli.

opencc-zeroDec 2013View details →

Data from: Zinc supplementation inhibits complement activation in age-related macular degeneration

Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. AMD is a multifactorial disorder but complement-mediated inflammation at the level of the retina plays a pivotal role. Oral zinc supplementation can reduce the progression of AMD but the precise mechanism of this protective effect is as yet unclear. We investigated whether zinc supplementation directly affects the degree of complement activation in AMD and whether there is a relation between serum complement catabolism during zinc administration and the complement factor H (CFH) gene or the Age-Related Maculopathy susceptibility 2 (ARMS2) genotype. In this open-label clinical study, 72 randomly selected AMD patients in various stages of AMD received a daily supplement of 50 mg zinc sulphate and 1 mg cupric sulphate for three months. Serum complement catabolism–defined as the C3d/C3 ratio–was measured at baseline, throughout the three months of supplementation and after discontinuation of zinc administration. Additionally, downstream inhibition of complement catabolism was evaluated by measurement of anaphylatoxin C5a. Furthermore, we investigated the effect of zinc on complement activation in vitro. AMD patients with high levels of complement catabolism at baseline exhibited a steeper decline in serum complement activation (p<0.001) during the three month zinc supplementation period compared to patients with low complement levels. There was no significant association of change in complement catabolism and CFH and ARMS2 genotype. In vitro zinc sulphate directly inhibits complement catabolism in hemolytic assays and membrane attack complex (MAC) deposition on RPE cells. This study provides evidence that daily administration of 50 mg zinc sulphate can inhibit complement catabolism in AMD patients with increased complement activation. This could explain part of the mechanism by which zinc slows AMD progression.

opencc-by-4.0Nov 2023View details →

Data for: "Insights into the various mechanisms by which Shewanella spp. induce and inhibit steel corrosion"

Open the record for dataset details and reuse information.

opencc-by-4.0Dec 2023View details →

RAW DATA for "Kalium channelrhodopsins effectively inhibit neurons in the small model animals"

Open the record for dataset details and reuse information.

opencc-by-4.0Feb 2024View details →

Data for LRRK2 kinase inhibition reverses G2019S mutation-dependent effects on tau pathology spread

Data that was analyzed and used to create figures in the paper.

opencc-by-4.0Dec 2024View details →

Unveiling the inhibition mechanism of host-defense peptide cathelicidin LL-37 on the amyloid aggregation of human islet amyloid polypeptide

Open the record for dataset details and reuse information.

opencc-by-4.0Oct 2021View details →

JNK inhibition in Rett Syndrome models

Datasets produced and used during the current study. Data are mean ± SEM.

opencc-zeroJan 2022View details →

Transcriptome for: MYB42 inhibits hypocotyl cell elongation by coordinating brassinosteroid homeostasis and signaling in Arabidopsis

The precise control of brassinosteroids (BRs) homeostasis and signaling is a prerequisite for hypocotyl cell elongation in plants. Little is known, however, of such regulators of BR homeostasis and signaling. Here, we have demonstrated that MYB42 negatively regulates hypocotyl elongation through partial inhibition of BRASSINAZOLE-RESISTANT 1 (BZR1) signaling and promotion of BR inactivation. Transgenic Arabidopsis plants repressing the expression of MYB42 and its paralog MYB85 (MYB85 RNAi;myb42) exhibited longer hypocotyls than wild-type (WT) plants in darkness, while MYB42 or MYB85 overexpression inhibits hypocotyl elongation. Hypocotyl length of MYB85 RNAi;myb42 plants can be resorted into WT level by MYB42 overexpression. MYB42 inhibits hypocotyl elongation by mediating BR signaling, because MYB42 expression is repressed with BR treatment and in the dominant BR mutant bzr1-1D, and mutation of both MYB42 and MYB85 enhances the dwarf phenotype of the BR receptor mutant bri1-5. BZR1 directly represses MYB42 expression in response to BR, and the hypocotyl length of bzr1-1D is reduced in MYB42 overexpression plants but increased in MYB85 RNAi;myb42 plants. These results show MYB42 is a negative target of BZR1. Transcriptome data revealed that a number of BZR1-induced genes associated with cell elongation are down-regulated by MYB42, suggesting that MYB42 may partially inhibit BZR1 signaling. In addition, MYB42 enlarges its action in BR signaling through feedback activation of the BR-inactivating enzyme DOGT1. The present study shows a MYB42-mediated multilevel system that contributes to fine regulation of BR-induced hypocotyl elongation.

opencc-by-4.0Jun 2020View details →

Selective Modulation of the Protease Activated Protein C Using Exosite Inhibiting Aptamers

Activated protein C (APC) is a serine protease with anticoagulant and cytoprotective activities. Nonanticoagulant APC mutants show beneficial effects as cytoprotective agents. To study, if such biased APC signaling can be achieved by APC-binding ligands, the aptamer technology has been used. A G-quadruplex-containing aptamer, G-NB3, has been selected that binds to the basic exosite of APC with a KD of 0.2 nM and shows no binding to APC-related serine proteases or the zymogen protein C. G-NB3 inhibits the inactivation of activated cofactors V and VIII with IC50 values of 11.6 and 13.1 nM, respectively, without inhibiting the cytoprotective and anti-inflammatory functions of APC as tested using a staurosporine-induced apoptosis assay and a vascular barrier protection assay. In addition, G-NB3 prolongs the plasma half-life of APC through inhibition of APC-serine protease inhibitor complex formation. These physicochemical and functional characteristics qualify G-NB3 as a promising therapeutic agent usable to enhance the cytoprotective functions of APC without increasing the risk of APC-related hemorrhage.

Figure 3 from: Laksmiani NPL, Widiantara IWA, Pawarrangan ABS (2022) Potency of moringa (Moringa oleifera L.) leaves extract containing quercetin as a depigmentation agent inhibiting the tyrosinase enzyme using in-silico and in-vitro assay. Pharmacia 69(1): 85-92. https://doi.org/10.3897/pharmacia.69.e73132

Figure 3 The interaction of hydrogen bonds between the target protein of the tyrosinase with kojic acid. a: docking conformation kojic acid to tyrosinase, b: 3D interaction visualization of tyrosinase amino acid residues with kojic acid, c: 2D interaction visualization of tyrosinase amino acid residues with kojic acid.

Figure 5 from: Laksmiani NPL, Widiantara IWA, Pawarrangan ABS (2022) Potency of moringa (Moringa oleifera L.) leaves extract containing quercetin as a depigmentation agent inhibiting the tyrosinase enzyme using in-silico and in-vitro assay. Pharmacia 69(1): 85-92. https://doi.org/10.3897/pharmacia.69.e73132

Figure 5 TLC-chromatogram of Moringa Leaves extract at UV 254 nm (A) and UV 366 nm (B). Quercetin standard 100, 200, 400, 800, 1600 and 3200 ng (1–6); Moringa Leaves Maceration extract (7); reflux extract (8), soxhlation extract (9); quercetin standard 800 ng (10–11); UV spectrum of spot with Rf 0.4 from quercetin standard (C); UV spectrum of spot with Rf 0.4 from maceration extract of Moringa Leaves (D); UV spectrum of spot with Rf 0.4 from soxhlation extract of Moringa Leaves (E).

Figure 1 from: Laksmiani NPL, Widiantara IWA, Pawarrangan ABS (2022) Potency of moringa (Moringa oleifera L.) leaves extract containing quercetin as a depigmentation agent inhibiting the tyrosinase enzyme using in-silico and in-vitro assay. Pharmacia 69(1): 85-92. https://doi.org/10.3897/pharmacia.69.e73132

Figure 1 Redocking visualization between tyrosinase enzyme and native ligand. 1: The structure of the tyrosinase enzyme (PDB ID: 2Y9X), 2a: tyrosinase enzyme structure without native ligand, 2b: native ligand (tropolone) structure, 3a: redocking conformation, 3b: 3D interaction of amino acid residues from tyrosinase enzyme with native ligand, 3c: 2D interaction of amino acid residues from tyrosinase enzyme with native ligand.

Figure 4 from: Laksmiani NPL, Widiantara IWA, Pawarrangan ABS (2022) Potency of moringa (Moringa oleifera L.) leaves extract containing quercetin as a depigmentation agent inhibiting the tyrosinase enzyme using in-silico and in-vitro assay. Pharmacia 69(1): 85-92. https://doi.org/10.3897/pharmacia.69.e73132

Figure 4 The interaction of hydrogen bonds between the target protein of the tyrosinase with quercetin. a: docking conformation between quercetin and tyrosinase, b: 3D interaction visualization of tyrosinase amino acid residues with quercetin, c: 2D interaction visualization of tyrosinase amino acid residues with quercetin.