Find research datasets worth reusing

opencc-by-4.0Dec 2021View details →

Statin therapy inhibits fatty acid synthase via dynamic protein modifications

Statins are a class of drugs widely prescribed to prevent cardiovascular disease, with pleiotropic cellular effects. Statins inhibit HMG-CoA reductase (HMGCR), which converts the metabolite HMG-CoA into mevalonate. Recent discoveries revealed HMG-CoA is a reactive metabolite that can non-enzymatically modify proteins and impact their activity. Therefore, we predicted that inhibition of HMGCR by statins might increase HMG-CoA levels and protein modifications. We observed a substantial increase in HMG-CoA levels upon statin treatment, and only a single protein was modified. Mass spectrometry revealed fatty acid synthase (FAS) was modified on active site residues, and surprisingly, the modification is located on non-lysine side-chains. The dynamic modifications occur only on a sub-pool of FAS near HMGCR and alter cellular signaling around the ER and Golgi. These results uncover communication between cholesterol and lipid biosynthesis by the substrate of one pathway inhibiting another in a rapid and reversible manner.

opencc-zeroMar 2022View details →

Host preferences inhibit transmission from potential superspreader host species

Host species that are particularly abundant, infectious, and/or infected tend to contribute disproportionately to symbiont (parasite or mutualist) maintenance in multi-host systems. Therefore, in a facultative multi-host system where two host species had high densities, high symbiont infestation intensities, and high infestation prevalence, we expected interspecific transmission rates to be high. Instead, we found that interspecific symbiont transmission rates to caged sentinel hosts were an order of magnitude lower than intraspecific transmission rates in the wild. Using laboratory experiments to decompose transmission rates, we found that opportunities for interspecific transmission were frequent, where interspecific and intraspecific contact rate functions were statistically indistinguishable. But most interspecific contacts did not lead to transmission events due to a previously unrecognized transmission barrier: strong host preferences. During laboratory choice experiments, the symbiont preferred staying on or dispersing to its current host species, even though the oligochaete symbiont is a globally distributed host generalist that can survive and reproduce on many snail species. These surprising results suggest that when managing symbiont transmission, identifying key host species is still important, but it may be equally important to identify and manage transmission barriers that keep potential superspreader host species in check.

opencc-by-4.0Apr 2022View details →

Metabolic data: Inhibition of mitochondrial complex I reverses NOTCH1-driven metabolic reprogramming in T-cell acute lymphoblastic leukemia

T-cell acute lymphoblastic leukemia (T-ALL) is commonly driven by activating mutations in NOTCH1 that facilitate glutamine oxidation. Here we identify oxidative phosphorylation (OxPhos) as a critical pathway for leukemia cell survival and demonstrate a direct relationship between NOTCH1, elevated OxPhos gene expression, and acquired chemoresistance in pre-leukemic and leukemic models. Disrupting OxPhos with IACS-010759, an inhibitor of mitochondrial complex I, causes potent growth inhibition through induction of metabolic shut-down and redox imbalance in NOTCH1-mutated and less so in NOTCH1-wt T-ALL cells. Mechanistically, inhibition of OxPhos induces metabolic reprogramming into glutaminolysis. We show that pharmacological blockade of OxPhos combined with inducible knock-down of glutaminase, the key glutamine enzyme, confers synthetic lethality in mice harboring NOTCH1-mutated T-ALL. We leverage this synthetic lethal interaction to demonstrate that IACS-010759 in combination with chemotherapy containing L-asparaginase, an enzyme that uncovers the glutamine dependency of leukemic cells, causes reduced glutaminolysis and profound tumor reduction in pre-clinical models of human T-ALL. In summary, this metabolic dependency of T-ALL on OxPhos provides a rational therapeutic target.

opencc-zeroMay 2022View details →

Elevated O3 inhibited isoprene emission of a diploid and a triploid genotype of Populus tomentosa by different mechanisms

Ozone (O3) pollution affects plant growth and isoprene (ISO) emission. However, the response mechanism of isoprene emission rate (ISOrate) to elevated O3 (EO3) remains poorly understood. ISOrate was investigated in two genotypes (diploid and triploid) of Chinese white poplar (Populus tomentosa Carr.) exposed to EO3 in an open top chamber (OTC) system. The triploid genotype had higher photosynthesis rate (A) and stomatal conductance (gs) than the diploid one. EO3 significantly decreased A, gs, and ISOrate of middle and lower leaf positions in both genotypes. In the diploid genotype, the reduction of ISOrate was caused by a systematic decrease related to ISO synthesis capacity, as indicated by decreased contents of isoprene precursor dimethylallyl diphosphate (DMADP) and isoprene synthase (ISPS) protein and activity of ISPS. On the other hand, the negative effect of O3 on ISOrate of the triploid genotype did not result from inhibited ISO synthesis capacity, but from increased ISO oxidative loss within the leaf. Our findings will be useful for breeding poplar genotypes with high-yield and lower ISOrate, depending on local atmospheric VOC/NOx ratio, to cope with both the rising O3 concentrations and increasing biomass demand. They can also enlighten the incorporation of O3 effects into process-based models of isoprene emission.

opencc-by-4.0May 2022View details →

Original data for publication: The Atomically Precise Gold/Captopril Nanocluster Au25(Capt)18 Gains Anticancer Activity by Inhibiting Mitochondrial Oxidative Phosphorylation

Original data for publication: The Atomically Precise Gold/Captopril Nanocluster Au25(Capt)18 Gains Anticancer Activity by Inhibiting Mitochondrial Oxidative Phosphorylation, ACS Applied Materials & Interfaces

opencc-by-4.0Jun 2022View details →

Data set for "Learning-related congruent and incongruent changes of excitation and inhibition in distinct cortical areas"

Data set for: Esmaeili V, Oryshchuk A, Asri R, Tamura K, Foustoukos G, Liu Y, Guiet R, Crochet S, Petersen CCH (2022) Learning-related congruent and incongruent changes of excitation and inhibition in distinct cortical areas. PLoS Biol 20: e3001667. doi: 10.1371/journal.pbio.3001667 There are 2 files in this upload: 1. The file named "2022_Esmaeili_PLOSBiol.pdf" is the Open Access pdf of the online publication in PLoS Biology. 2. The file named "Esmaeili_data_code.zip" (~3 GB) is a zipped version of a folder "Esmaeili_data_code" (~3 GB), which contains four subfolders named as “data”, “codes”, “figures” and “excel files” and a README.txt file with the descriptions of files and required toolboxes to run the codes. To access the data and codes, first unzip the file. The “code” subfolder contains all the Matlab codes and their dependencies for generating all the main and supplementary figures. The “data” subfolder contains the data analysed in the study used to generate different figures. When running the code, you will have to select the path of the unzipped data containing the subfolders data, code, figures and excel files (\Esmaeili_data_code\). Some parts of the code rely upon previous results, and need to be executed sequentially in the order of the figure panels in the journal publication. Running the codes will save the figure panels and the related excel files in the “figures” and “excel files” subfolders respectively.

opencc-zeroAug 2022View details →

Temperature shifts associated with bat arousals during hibernation inhibit the growth of Pseudogymnoascus destructans

Temperature is a critically important factor in many infectious disease systems because it can regulate responses in both the host and the pathogen. White-nose syndrome (WNS) in bats is a severe infectious disease caused by the temperature-sensitive fungus, Pseudogymnoascus destructans (Pd). One feature of WNS is an increase in the frequency of arousal bouts (i.e., when bat body temperatures are elevated) in Pd-infected bats during hibernation. While several studies have proposed that increased frequency of arousals may play a role in the pathophysiology of WNS, it is unknown if the temperature fluctuations might mediate Pd growth. We hypothesized that exposure to a high frequency of elevated temperatures would reduce Pd growth due to thermal constraints on the pathogen. We simulated the thermal conditions for arousal bouts of uninfected and infected bats during hibernation (fluctuating from 8 - 25 °C at two different rates) and quantified Pd growth in vitro. We found that increased exposure to high temperatures significantly reduced Pd growth. Because temperature is one of the most critical abiotic factors mediating host-pathogen interactions, resolving how Pd responds to fluctuating temperatures will provide insights for understanding WNS in bats and other fungal diseases.

opencc-zeroSep 2022View details →

Data from: A causal role of anterior prefrontal-putamen circuit for response inhibition revealed by transcranial ultrasound stimulation in humans

Stopping an inappropriate response requires the involvement of the prefrontal-subthalamic hyperdirect pathway. However, how the prefrontal-striatal indirect pathway contributes to stopping is poorly understood. In this study, transcranial ultrasound stimulation is used to perform interventions in a task-related region in the striatum. Functional magnetic resonance imaging (MRI) reveals activation in the right anterior part of the putamen during response inhibition, and ultrasound stimulation to the anterior putamen, as well as the subthalamic nucleus, results in significant impairments in stopping performance. Diffusion imaging further reveals prominent structural connections between the anterior putamen and the right anterior part of the inferior frontal cortex (IFC), and ultrasound stimulation to the anterior IFC also shows significant impaired stopping performance. These results demonstrate that the right anterior putamen and right anterior IFC causally contribute to stopping and suggest that the anterior IFC-anterior putamen circuit in the indirect pathway serves as an essential route for stopping.

opencc-zeroAug 2022View details →

AAA+ ATPase Thorase Inhibits mTOR Signaling Through the Disassembly of the mTOR Complex 1

The mechanistic target of rapamycin (mTOR) signals through the mTOR complex 1 (mTORC1) and the mTOR complex 2 to maintain cellular and organismal homeostasis. Failure to finely tune mTOR activity results in metabolic dysregulation and disease. While there is substantial understanding of the molecular events leading mTORC1 activation at the lysosome, remarkably little is known about what terminates mTORC1 signaling. Here, we show that the AAA+ ATPase Thorase directly binds mTOR, thereby orchestrating the disassembly and inactivation of mTORC1. Thorase disrupts the association of mTOR to Raptor at the mitochondria-lysosome interface and this action is sensitive to amino acids. Lack of Thorase causes accumulation of mTOR-Raptor complexes and altered mTORC1 disassembly/re-assembly dynamics upon changes in amino acid availability. The resulting excessive mTORC1 can be counteracted with rapamycin in vitro and in vivo. Collectively, we reveal Thorase as a key component of the mTOR pathway that disassembles and thus inhibits mTORC1.

opencc-by-4.0Sep 2022View details →

Use of A Molecular Switch Probe to Activate or Inhibit GIRK1 Heteromers In Silico Reveals a Novel Gating Mechanism

GIRK channel structure models (PDB structure files) used for Molecular Dynamics simulations.

opencc-by-4.0Sep 2022View details →

"Efficacy of Plant-derived Fungicides at Inhibiting Batrachochytrium salamandrivorans Growth" Dataset and Code

The emerging fungal amphibian pathogen, Batrachochytrium salamandrivorans (Bsal), is currently spreading across Europe and given its estimated invasion potential, has the capacity to decimate salamander populations worldwide. Fungicides are a promising in situ management strategy for Bsal due to their ability to treat the environment and infected individuals. However, antifungal drugs or pesticides could adversely affect the environment and non-target hosts, thus identifying safe, effective candidate fungicides for in situ treatment is needed. Here, we estimated the inhibitory fungicidal efficacy of five plant-derived fungicides (thymol, curcumin, allicin, 6-gingerol, and Pond Pimafix®) and one chemical fungicide (Virkon® Aquatic) against Bsal zoospores in vitro. We used a broth microdilution method in 48-well plates to test the efficacy of six concentrations per fungicide on Bsal zoospore viability. Following plate incubation, we performed cell viability assays and agar plate growth trials to estimate the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of each fungicide. All six fungicides exhibited inhibitory and fungicidal effects against Bsal growth, with estimated MIC concentrations ranging from 60 to 0.156 μg/mL for the different compounds. Allicin showed the greatest efficacy (i.e., lowest MIC and MFC) against Bsal zoospores followed by curcumin, Pond Pimafix®, thymol, 6-gingerol, and Virkon® Aquatic, respectively. Our results provide evidence that plant-derived fungicides are effective at inhibiting and killing Bsal zoospores in vitro and may be useful for in situ treatment. Additional studies are needed to estimate the efficacy of these fungicides at inactivating Bsal in the environment and treating Bsal-infected amphibians.

opencc-by-4.0Jan 2018View details →

Data from "Effects of a brief mindfulness-meditation intervention on neural measures of response inhibition in cigarette smokers", Plos One 2017

32-channel(+8) raw data (Biosemi Active two, 10-20, 512Hz) unfiltered from the 2018 Plos ONE paper "Effects of a brief mindfulness-meditation intervention on neural measures of response inhibition in cigarette smokers"

opencc-by-4.0Nov 2017View details →

INHIBITION OF NITRIC OXIDE SYNTHESIS PROMOTES INCREASED MORTALITY DESPITE REDUCTION OF PARASITEMIA IN Plasmodium berghei-INFECTED MICE

Backgrounds: Nitric oxide (NO) is an important mediator molecule in inflammatory processes, but its role in the pathophysiology of malaria is still uncertain. Methods: To investigate the NO synthesis inhibition on the oxidative changes induced by Plasmodium berghei infection in mice, malaria was induced in 150 animals, of which 75 animals were treated with NO inhibitor L-NAME; the remaining are sham controls. All animals underwent euthanasia after 1, 5, 10, 15 or 20 days after the infection for the collection of lungs, brain, and blood. Parasitemia was determined and the survival of the animals evaluated. Tissue samples were assayed for nitrites and nitrates (NN), thiobarbituric acid reactive substances (TBARS), and total Trolox equivalent antioxidant capacity (TEAC). A histopathological study was performed. Results: Mortality rates in the L-NAME were always higher in relation to the controls. In brains, NN was lower in groups L-NAME. Parasitemia and its progression rate were greater in control groups. From the 5th day of infection, mice treated with L-NAME showed cerebral edema and interstitial pneumonia of greater intensity than controls. Conclusions: Anti-inflammatory and hemodynamic effects of NO surpasses its pro-oxidant role in murine malaria. Backgrounds: Nitric oxide (NO) is an important mediator molecule in inflammatory processes, but its role in the pathophysiology of malaria is still uncertain. Methods: To investigate the NO synthesis inhibition on the oxidative changes induced by Plasmodium berghei infection in mice, malaria was induced in 150 animals, of which 75 animals were treated with NO inhibitor L-NAME; the remaining are sham controls. All animals underwent euthanasia after 1, 5, 10, 15 or 20 days after the infection for the collection of lungs, brain, and blood. Parasitemia was determined and the survival of the animals evaluated. Tissue samples were assayed for nitrites and nitrates (NN), thiobarbituric acid reactive substances (TBARS), and total Trolox equivalent antioxidant capacity (TEAC). A histopathological study was performed. Results: Mortality rates in the L-NAME were always higher in relation to the controls. In brains, NN was lower in groups L-NAME. Parasitemia and its progression rate were greater in control groups. From the 5th day of infection, mice treated with L-NAME showed cerebral edema and interstitial pneumonia of greater intensity than controls. Conclusions: Anti-inflammatory and hemodynamic effects of NO surpasses its pro-oxidant role in murine malaria.

opencc-zeroApr 2024View details →

Mutant IDH1 inhibition induces dsDNA sensing to activate tumor immunity

Isocitrate Dehydrogenase 1 (IDH1) is the most commonly mutated metabolic gene across human cancers. Mutant IDH1 (mIDH1) generates the oncometabolite (R)-2-hydroxyglutarate, disrupting enzymes involved in epigenetics and other processes. A hallmark of IDH1-mutant solid tumors is T cell exclusion, whereas mIDH1 inhibition in preclinical models restores anti-tumor immunity. Here, we define a cell-autonomous mechanism of mIDH1-driven immune evasion. IDH1-mutant solid tumors show striking, selective hypermethylation and silencing of the cytoplasmic dsDNA sensor, CGAS, compromising innate immune signaling. mIDH1 inhibition restores DNA demethylation, derepressing CGAS and transposable element (TE) subclasses. dsDNA produced by TE-reverse transcriptase activates cGAS, triggering viral mimicry and stimulating anti-tumor immunity. Thus, we demonstrate that mIDH1 epigenetically suppresses innate immunity and link endogenous reverse transcriptase activity to the mechanism of action of an FDA-approved oncology drug.

AL589863.1 inhibits the progression of pancreatic cancer through regulating miR-671-5p/THBS1 axis

We obtained <a name="OLE_LINK1"></a>mRNA and lncRNA expression profiles from 178 PC tissues and 4 normal pancreatic tissues in the TCGA database. We further downloaded the high throughput database of 167 normal tissues of the pancreas in the GTEx database. Then, the TCGA and GTEx datasets were integrated for further analysis. Three microarray datasets, including mRNA (GSE15471 and GSE62165) and miRNA (<a name="OLE_LINK2"></a>GSE32678), were downloaded from the GEO database. GSE15471 contained 39 pairs of <a name="OLE_LINK41"></a>pancreatic ductal adenocarcinoma tumors (PDAC) and adjacent normal tissues. GSE62165 included 118 PDAC and 13 adjacent normal samples. GSE32678 covered 25 PC samples and 7 adjacent normal samples.  The Limma package in R was carried out to identify DEGs, <a name="_Hlk146015254"></a>DEmiRNAs, and DEl<a name="OLE_LINK4"></a>ncRNAs. We identified the DEGs with threshold values of |log 2 FC|> 1.5 and adjusted. <a name="OLE_LINK3"></a>p-value< 0.05. DEmiRNAs and DElncRNAs were determined with <a name="_Hlk146015501"></a>|log 2 FC|> 1.5/2.0 and p-value< 0.05. Additionally, volcano plots were drawn to better visualize these DElncRNAs, DEmiRNAs, and DEGs using R software.

Adaptative Survival of Aspergillus fumigatus to Echinocandins Arises from Cell Wall Remodeling Beyond β-1,3-glucan Synthesis Inhibition

Unprocessed Solid-state NMR and Molecular Dynamics data sets for the manuscript titled "Adaptative Survival of Aspergillus fumigatus to Echinocandins Arises from Cell Wall Remodeling Beyond β-1,3-glucan Synthesis Inhibition"

Molecular Dynamics Simulation and Docking Studies Reveals Inhibition of NF-kB signaling as a Promising Therapeutic Drug Target for reduction in Cytokines Storms

The complexes of the top identified molecules with NF-kB-kB site, as well as all the designed molecules used in the screening process.

Data of Fig 4 "Assessment of the potential risk of oteseconazole and two other tetrazole antifungals to inhibit adrenal steroidogenesis and peripheral metabolism of corticosteroids"

Dataset containes all data of Figure 4 of the publication "Assessment of the potential risk of oteseconazole and two other tetrazole antifungals to inhibit adrenal steroidogenesis and peripheral metabolism of corticosteroids" (DOI: 10.3389/fphar.2024.1394846)

Figure 5 "Assessment of the potential risk of oteseconazole and two other tetrazole antifungals to inhibit adrenal steroidogenesis and peripheral metabolism of corticosteroids"

Dataset containes all data of Figure 5 of the publication "Assessment of the potential risk of oteseconazole and two other tetrazole antifungals to inhibit adrenal steroidogenesis and peripheral metabolism of corticosteroids" (DOI: 10.3389/fphar.2024.1394846)

Dataset of Fig 3 "Assessment of the potential risk of oteseconazole and two other tetrazole antifungals to inhibit adrenal steroidogenesis and peripheral metabolism of corticosteroids"

Dataset containes all data of Figure 3 of the publication "Assessment of the potential risk of oteseconazole and two other tetrazole antifungals to inhibit adrenal steroidogenesis and peripheral metabolism of corticosteroids" (DOI: 10.3389/fphar.2024.1394846)