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6,818 results for “inhibition”
Sedimentation inhibits macroalgal priming on an emergent plant decomposition in the littoral zone of an eutrophic lake, China
<p>The data presented in this manuscript (MS# 2020JG005630) are original and are available in zondo.</p>
Function and evolution of B-Raf loop dynamics relevant to cancer recurrence under drug inhibition
<p>Oncogenic mutations in the kinase domain of the B-Raf protein have long been associated with cancers involving the RAF-MEK-ERK pathway. One constitutive ERK activating mutation in B-Raf, the V600E (valine to glutamate) replacement occurring adjacent to a site of threonine phosphorylation (T599) occurs in many types of cancer, and in a large percentage of certain cancers, such as melanoma. Because natural ATP binding activity and the V600E mutation are both known to alter the physical behavior of the activation loop in the ATP binding domain, this system is especially amenable to comparative functional analyses using molecular dynamics of drug classes and genetic variants at all-atom resolution. Here, we employ machine learning enabled identification of functionally conserved protein dynamics to compare how disease pertinent molecular variations impact conserved loop dynamics during the binding of four ATP competitive B-Raf inhibitors (sorafenib, vemurafenib, dabrafenib, and PLX7904) that differ in their effectiveness in preventing cancer recurrence. We demonstrate that drug development targeting B-Raf has progressively moved towards ATP competitive inhibitors that demonstrate less tendency to mimic the functional dynamic shifts associated with ATP binding in this domain. We argue this functional dynamic mimicry in first generation B-Raf inhibitors increases the side effect of hyperactivation (i.e. inducing MAPK activation in non-tumorous cells in the absence of secondary mutation). Within the context of the binding interaction of each inhibitor, we compare the functional dynamic impacts of V600E and other sensitizing and drug resistance causing mutations in the activation and P-loops, confirming sites of low mutational tolerance in these two functional regions. Lastly, we investigate V600E sensitivity of B-Raf loop dynamics in an evolutionary context, demonstrating that while it probably shares partial origin with its early evolution in primitive eukaryotes, the functional sensitivity to V600E was secondarily increased during early jawed vertebrate evolution.</p>
QSAR dataset for anti melanogenic agents - tyrosinase inhibition
<p>Kindly cite if you are using the dataset for predicting the tyrosinase inhibitory activity for your compounds.</p> <p>We generated a validated QSAR model with a dataset consisting of 69 thio-semicarbazone derivatives to elucidate the physicochemical properties of compounds essential for tyrosinase inhibition and to identify novel lead molecules with enhanced tyrosinase inhibitory activity and bioavailability.</p> <p> </p> <p>Thanks,</p> <p>Authors</p>
Data from: The enemy within: how does a bacterium inhibit the foraging aptitude and risk management behavior of Allenby's gerbils?
<p>Microbes inhabiting multi-cellular organisms have complex, often subtle effects on their hosts. <i>Gerbillus andersoni allenbyi </i>are commonly infected with the <i>Mycoplasma haemomuris-</i>like bacteria, which may cause mild nutrient (choline, arginine) deficiencies. However, are there more serious ecological consequences of infection such as effects on foraging aptitudes and risk management? We tested alternatives: 1) <i>nutrient compensation hypothesis</i>, does nutrient deficiency induce infected gerbils to make up for the shortfall by foraging more and taking greater risks? or 2) <i>lethargy hypothesis</i>, do sick gerbils forage less, and are they compromised in their ability to detect predators or risky microhabitats? We compared the foraging and risk management behavior of infected and non-infected gerbils. We experimentally infected gerbils with the bacteria, which allowed us to compare between non-infected, acutely infected (peak infection loads), and chronically infected (low infection loads) individuals. Our findings supported the <i>lethargy hypothesis </i>over the <i>nutrient compensation hypothesis. </i>Infected individuals incurred dramatically elevated foraging costs, including less efficient foraging, diminished "quality" of time spent vigilant, and increased owl predation. Interestingly, gerbils that were chronically infected (lower bacteria load) experienced larger ecological costs than acutely infected individuals (i.e. peak infection loads). This suggests that the debilitating effects of infection occur gradually, with a progressive decline in the quality of time gerbils allocated to foraging and managing risk. These increased long-term costs of infection demonstrate how small direct physiological costs of infection can lead to large indirect ecological costs. The indirect ecological costs of this parasite appear much greater than the direct physiological costs.</p>
Data from: Spatial structure maintains diversity of pyocin inhibition in household Pseudomonas aeruginosa
<p><span><span><span><span><span><span><span><span><span><span><span>Nearly all bacteria produce narrow-spectrum antibiotics called bacteriocins. Studies have shown that bacteriocins can mediate microbial interactions, but the mechanisms underlying patterns of inhibition are less well understood. We assembled a spatially structured collection of isolates of <i>Pseudomonas aeruginosa</i> from bathroom and kitchen sink drains in nine households. Growth inhibition of these <i>P. aeruginosa </i>by bacteriocins, known as pyocins in this species, was measured using pairwise inhibition assays. Carbon source usage of these isolates was measured and genetic distance was estimated using multilocus sequencing. We found that as the distance between sites of isolation increased, there was a significantly higher probability of inhibition, and that pyocin inhibition and susceptibility vary greatly among isolates collected from different houses. We also detected support for other mechanisms influencing diversity: inhibition outcomes were influenced by the type of drain from which isolates were collected, and while we found no indication that carbon source utilization influences inhibition, inhibition was favored at an intermediate genetic distance. Overall, these results suggest that the combined effects of dispersal limitation among sites and competitive exclusion within them maintain diversity in pyocin inhibition and susceptibility phenotypes, and that additional processes such as local adaptation and effects of phylogenetic distance could further contribute to spatial variability.</span></span></span></span></span></span></span></span></span></span></span></p>
Inhibition of Cdc42 activity extends lifespan and decreases circulating inflammatory cytokines in aged female C57BL/6 mice
<p>Cdc42 is a small RhoGTPase regulating multiple functions in eukaryotic cells. The activity of Cdc42 is significantly elevated in several tissues of aged mice, while the Cdc42 gain-of-activity mouse model presents with a pre-mature aging-like phenotype and with decreased lifespan. These data suggest a causal connection between elevated activity of Cdc42, aging and reduced lifespan. Here, we demonstrate that systemic treatment of aged (75-week old) female C57BL/6 mice with a Cdc42 activity specific inhibitor (CASIN) for 4 consecutive days significantly extends average and maximum lifespan. Moreover, aged CASIN-treated animals displayed a youthful level of the aging-associated cytokines IL-1b, IL-1a and INFg in serum and a significantly younger epigenetic clock as based on DNA methylation levels in blood cells. Overall, our data show that systemic administration of CASIN to reduce Cdc42 activity in aged mice extends murine lifespan.</p>
Plasticity of GABA Inhibition in the Early Visual Cortex of Human Adults: Exp1 dataset
<p>Dataset from Exp1 in "Proulx, Sébastien, Sheynin, Yasha, Hess, Robert, & Farivar, Reza. (2020). Plasticity of GABA Inhibition in the Early Visual Cortex of Human Adults (in preparation).</p> <p>Metadata included in the 'data' variable of the exp1Data.mat file.</p>
Inhibition of firefly luciferase activity by a HIF prolyl hydroxylase inhibitor
<p>The three hypoxia-inducible factor (HIF) prolyl-4-hydroxylase domain (PHD) 1–3 enzymes confer oxygen sen-sitivity to the HIF pathway and are novel therapeutic targets for treatment of renal anemia. Inhibition of thePHDs may further be beneficial in other hypoxia-associated diseases, including ischemia and chronic in-flammation. Several pharmacologic PHD inhibitors (PHIs) are available, but our understanding of their selectivity and its chemical basis is limited.We here report that the PHI JNJ-42041935 (JNJ-1935) is structurally similar to the firefly luciferase substrate D-luciferin. Our results demonstrate that JNJ-1935 is a novel inhibitor of firefly luciferase enzymatic activity. In contrast, the PHIs FG-4592 (roxadustat) and FG-2216 (ICA,BIQ,IOX3,YM311) did not affect firefly luciferase. The JNJ-1935 mode of inhibition is competitive with a Ki of 1.36 μM. D-luciferin did not inhibit the PHDs, despite its structural similarity to JNJ-1935. This study provides insights into a previously unknown JNJ-1935 off-target effect as well as into the chemical requirements for firefly luciferase and PHD inhibitors and may inform the development of novel compounds targeting these enzymes.</p>
Data from: Niche differentiation of bacterial versus archaeal soil nitrifiers induced by ammonium inhibition along a management gradient
<p>Soil nitrification, mediated mainly by ammonia oxidizing archaea (AOA) and bacteria (AOB), converts ammonium (NH4+) to nitrite (NO2−) and thence nitrate (NO3−). To better understand ecological differences between AOA and AOB, we investigated the nitrification kinetics of AOA and AOB under eight replicated cropped and unmanaged ecosystems (including two fertilized natural systems) along a long-term management intensity gradient in the upper U.S. Midwest. For five of eight ecosystems, AOB but not AOA exhibited Haldane kinetics (inhibited by high NH4+ additions), especially in perennial and successional systems. In contrast, AOA predominantly exhibited Michaelis-Menten kinetics, suggesting greater resistance to high nitrogen inputs than AOB. These responses suggest the potential for NH4+-induced niche differentiation between AOA and AOB. Additionally, long-term fertilization significantly enhanced maximum nitrification rates (Vmax) in the early successional systems for both AOA and AOB, but not in the deciduous forest systems. This was likely due to pH suppression of nitrification in the acidic forest soils, corroborated by a positive correlation of Vmax with soil pH but not with amoA gene abundance. Results also demonstrated that soil nitrification potentials were relatively stable, as there were no seasonal differences. Overall, results suggest that (1) NH4+ inhibition of AOB but not AOA could be another factor contributing to niche differentiation between AOA and AOB in soil, and (2) nitrification by both AOA and AOB can be significantly promoted by long-term nitrogen inputs.</p>
Inhibition mechanism and antibacterial activity of natural antibacterial agent citral on bamboo mold and its anti- mildew effect on bamboo
<p><span><span>Bamboo, a natural material, has been widely used in the fields of decoration, architecture and furniture. However, bamboo is easy to mildew and lose its use value. In this paper, inhibition mechanism and antibacterial activity of natural antibacterial agent citral on bamboo mold and its anti- mildew effect on bamboo were studied. The results showed that citral could change the shape of mycelium, destroy the integrity of mycelium structure, cell wall, and cell membrane structure, thereby causing leakage of nucleic acid, protein, and other substances in the cell, as well as destroy the pH balance of the inside and outside of the cell, to inhibit or kill mold. When the concentration of citral is 100mg/mL, the antibacterial rates of citral against <i>Penicillium citrinum </i>(PC), <i>Trichoderma viride</i> (TV), <i>Aspergillus niger</i> (AN) and a hybrid fungi group comprising PC, TV, and AN (Hun) were more than 100%. However, compared with the direct effect of citral on mold, the antibacterial property of bamboo treated with citral was significantly reduced, the mildew proof effect can be achieved only if the concentration of citral to treat bamboo is increased to more than 2 times of the concentration of citral directly acting on mold.</span></span></p>
Traffic noise inhibits cognitive performance in a songbird
<p>Noise pollution is commonly associated with human environments and mounting evidence indicates that noise has a variety of negative effects on wildlife. Noise has also been linked to cognitive impairment in humans and because many animals use cognitively-intensive processes to overcome environmental challenges, noise pollution has the potential to interfere with cognitive function in animals living in urban areas or near roads. We experimentally examined how road traffic noise impacts avian cognitive performance by testing adult zebra finches (Taeniopygia guttata) on a battery of foraging tasks in the presence or absence of traffic noise playback. Here we show that traffic noise reduces cognitive performance, including inhibitory control, motor learning, spatial memory, and social learning, but not associative color learning. This study demonstrates a novel mechanism through which anthropogenic noise can impact animals, namely through cognitive interference, and suggests that noise pollution may have previously unconsidered consequences for animals.</p>
Data from: Peptides derived from cadherin juxtamembrane region inhibit platelet function
The juxtamembrane domains (JMD) of transmembrane proteins are rich in critical peptide sequences that participate in dynamic cell signaling events. Synthetic JMD peptides derived from cadherin cell adhesion proteins have previously been shown to modulate platelet function. In this study, we aimed to develop functional bioactive agents from bioinformatically-identified critical peptide sequences. We synthesized overlapping 12-15 amino acids peptides from E- and N-cadherin JMD and assessed their effect on platelet aggregation and platelet ATP secretion. Peptides derived from close to the membrane proximal region inhibit platelet function. Sequential deletion of amino acids from the N- and C-termini of the inhibitory E-cadherin peptides identified the short K756EPLLP763 motif as a critical bioactive sequence. Alanine scanning studies further identified that the dileucine (LL) motif and positively charged lysine (K) are crucial for peptide activity. Moreover, scrambled peptides failed to show any effect on platelet activity. We conclude that peptides derived from JMD of E-cadherin provide potential lead peptides for the development of anti-thrombotic agents and to enable further understanding of the role of cadherins in platelet function.
Data from: Intraspecific predator inhibition, not a prey size refuge, enables oyster population persistence during predator outbreaks
Predators commonly structure natural communities, but predation effects can vary greatly. For example, increasing predator densities may not reduce prey populations as expected if intraspecific predator interactions suppress foraging efficiency or if prey size refuges exist. In northeastern Florida (USA), outbreaks of the predatory crown conch Melongena corona have contributed to declines in oyster populations and the commercial oyster fishery. However, despite expectations of oyster population collapse, reefs have persisted, albeit with reduced adult oyster size and living reef biomass. To investigate the mechanism(s) underlying this unexpected persistence, we used field observations and experiments to examine the effects of predator density and prey size on predation rates. Multi-year surveys indicated that large oysters did not experience a predation size refuge, and further suggested that predation rates declined with increased predator density. Consistent with field surveys, field experiments demonstrated that conchs selectively consumed larger oysters (potentially explaining the absence of large oysters on natural reefs) and that high conch densities suppressed per capita predation rates, likely due to intraspecific antagonistic interactions. A Type III ratio-dependent model best described the experimental conch functional response, explaining >50% of the variation in per capita prey consumption and including a signal of reduced attack rates at high predator densities. Thus, although large aggregations of predators have the potential to deplete prey populations, our study illustrates intraspecific predator interactions that possibly prevent the local extirpation of an important habitat-forming prey species.
Data from: CRISPR-Cas9 mediated CD133 knockout inhibits colon cancer invasion through reduced epithelial-mesenchymal transition
We previously reported that CD133, as a putative cancer stem cell marker, plays an important role in cell proliferation and invasion in colon cancer. To understand the role of CD133 expression in colon cancer, we evaluated the inhibitory effect of CD133 in colon cancer cells. In this study, we generated CD133knockout colon cancer cells (LoVo) using the CRISPR-Cas9 gene editing system. CD133+ colon cancer cells (LoVo) were infected with the lentiviral vector carrying CD133 gRNA and purified cell by culturing single cell colonies. CD133knockout cells was validated by western blot and flow cytometry analysis. In functional study, we observed a significant reduction in cell proliferation and colony formation in CRISPR-Cas9 mediated CD133 knockout cells in compare with control (P < 0.001). We also found the anticancer effect of stattic was dependent on CD133 expression in colon cancer cells. Although CD133knockout cells could not completely block the tumorigenic property, they showed remarkable inhibitory effects on the ability of cell migration and invasion (P < 0.001). In addition, we examined the epithelial mesenchymal transition (EMT)-related protein expression by western blot. The result clearly showed a loss of vimentin expression in CD133knockout cells. Therefore, CRISPR-Cas9 mediated CD133knockout can be an effective treatment modality for CD133+ colon cancer through reducing the characteristics of cancer stem cells.
Data from: Temporally autocorrelated environmental fluctuations inhibit the evolution of stress tolerance
As global environmental conditions continue to change at an unprecedented rate many species will experience increases in natural and anthropogenic stress. Generally speaking, selection is expected to favor adaptations that reduce the negative impact of environmental stress (i.e., stress tolerance). However, natural environmental variables typically fluctuate, exhibiting various degrees of temporal autocorrelation, known as environmental 'colors,' which may complicate evolutionary responses to stress. Here we combine experiments and theory to show that temporal environmental autocorrelation can determine long-term evolutionary responses to stress, without affecting the total amount of stress experienced over time. Experimental evolution of RNA virus lineages in differing environmental autocorrelation treatments agreed closely with predictions from our theoretical models that stress tolerance is favored in less autocorrelated (whiter) environments but disfavored in more autocorrelated ('redder)ned' environments. This is explained by an interaction between environmental color autocorrelation and a phenotypic tradeoff between stress tolerance and reproductive ability. The degree to which environmental color autocorrelation influences evolutionary trajectories depends on the shape of this tradeoff as well as the relative level of tolerance exhibited by novel mutants. These results suggest that long-term evolutionary dynamics depend not only on the overall strength of selection, but also on the way that selection is distributed over time.
Data from: Artificial night lighting inhibits feeding in moths
One major, yet poorly studied, change in the environment is nocturnal light pollution, which strongly alters habitats of nocturnally active species. Artificial night lighting is often considered as driving force behind rapid moth population declines in severely illuminated countries. To understand these declines, the question remains whether artificial light causes only increased mortality or also sublethal effects. We show that moths subjected to artificial night lighting spend less time feeding than moths in darkness, with the shortest time under light conditions rich in short wavelength radiation. These findings provide evidence for sublethal effects contributing to moth population declines. Because effects are strong under various types of light compared with dark conditions, the potential of spectral alterations as a conservation tool may be overestimated. Therefore, restoration and maintenance of darkness in illuminated areas is essential for reversing declines of moth populations.
Microsaccades inhibition triggered by a repetitive visual distractor is not subject to habituation: implications for the programming of reflexive saccades
<p>Dataset relative to the manuscript entitled "<strong>Microsaccades inhibition triggered by a repetitive visual distractor is not subject to habituation: implications for the programming of reflexive saccades</strong>"</p>
BX-795 inhibits HSV-1 and HSV-2 replication in a JNK/p38-dependent manner, but not through interfering PDK1 activity
<p>The two files contain the methods and result data of submitted paper, <em>BX-795 inhibits HSV-1 and HSV-2 replication in a JNK/p38-dependent manner, but not through interfering PDK1 activity.</em></p>
Dataset of "Vertical pathway inhibition of receptor tyrosine kinases and BAD with synergistic efficacy in triple negative breast cancer"
Open the record for dataset details and reuse information.
Data from Differential Inhibition of Intra- and Inter- Molecular Protease Cleavages by Antiviral Compounds
<p>Updated gel images to correspond to specific figures</p>
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