Apoptosis signal-regulating kinase 1 (ASK1) is a serine-threonine kinase that is ubiquitously expressed in nucleated cells and is responsible for the activation of multiple mitogen-activated protein ...kinases (MAPK) to regulate cell stress. Activation of ASK1 via cellular stress leads to activation of downstream signaling components, activation of transcription factors, and proinflammatory cytokine production. ASK1 is also expressed in anucleate platelets and is a key player in platelet activation as it is important for signaling. Interestingly, the mechanism of ASK1 activation is cell type-dependent. In this review we will explore how ASK1 regulates a variety of cellular processes from innate immune function to thrombosis and hemostasis. We will discuss how ASK1 influences FcγRIIA-mediated platelet reactivity and how that reactivity drives platelet clearance. Furthermore, we will explore the role of ASK1 in thromboxane (TxA
) generation, which highlights differences in the way ASK1 functions in mouse and human platelets.
Bitter gourd (Momordica charantia L.) is a nutritious vegetable crop of Asian origin, used as a medicinal herb in Indian and Chinese traditional medicine. Molecular breeding in bitter gourd is in its ...infancy, due to limited molecular resources, particularly on functional markers for traits such as gynoecy. We performed de novo transcriptome sequencing of bitter gourd using Illumina next-generation sequencer, from root, flower buds, stem and leaf samples of gynoecious line (Gy323) and a monoecious line (DRAR1). A total of 65,540 transcripts for Gy323 and 61,490 for DRAR1 were obtained. Comparisons revealed SNP and SSR variations between these lines and, identification of gene classes. Based on available transcripts we identified 80 WRKY transcription factors, several reported in responses to biotic and abiotic stresses; 56 ARF genes which play a pivotal role in auxin-regulated gene expression and development. The data presented will be useful in both functions studies and breeding programs in bitter gourd.
Stellar streams in chameleon gravity Naik, A. P.; Evans, N. W.; Puchwein, E. ...
Physical review. D,
10/2020, Letnik:
102, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Theories of gravity that incorporate new scalar degrees of freedom typically require "screening mechanisms" to ensure consistency with Solar System tests. One widely studied mechanism-the chameleon ...mechanism-can lead to violations of the equivalence principle (EP), as screened and unscreened objects fall differently. If the stars are screened but the surrounding dark matter is not, EP violation can lead to asymmetry between leading and trailing streams from tidally disrupted dwarf galaxies in the Milky Way halo. We provide analytic estimates of the magnitude of this effect for realistic Galactic mass distributions, demonstrating that it is an even more sensitive probe than suggested previously. Using a restricted N-body code, we simulate four satellites with a range of masses and orbits, together with a variety of strengths of the fifth force and screening levels of the Milky Way and satellite. The ratio of the cumulative number function of stars in the leading and trailing stream as a function of longitude from the satellite is computable from simulations and measurable from the stellar data and can provide a direct test of chameleon gravity. We forecast constraints for streams at large Galactocentric distances, which probe deeper into chameleon parameter space, using the specific example case of Hu-Sawicki f(R) gravity. Streams in the outer reaches of the Milky Way halo (with apocenters between 100 and 200 kpc) provide easily attainable constraints at the level of |fR0| = 10−7. Still more stringent constraints at the level of 10−7.5 or even 10−8 are plausible provided the environmental screening of the satellite is accounted for, and screening of the Milky Way's outer halo by the Local Group is not yet triggered in this range. These would be among the tightest astrophysical constraints to date. We note three further signatures of chameleon gravity: (i) the trailing stellar stream may become detached from the dark matter progenitor if all the stars are lost, (ii) in the extreme fifth force regime, striations in the stellar trailing tail may develop from material liberated at successive pericentric passages, and (iii) if the satellite is fully screened, its orbital frequency is lower than that of the associated dark matter, which is preferentially liberated into the leading tidal tail.
Purpose: To correlate the severity of meibomian gland dysfunction (MGD) with the serum lipoprotein levels. Methods: The study was conducted as a prospective observational study over a period of 18 ...months. Ninety patients diagnosed with MGD were enrolled after they gave their informed consent according to the inclusion-exclusion criteria. Meibomian gland status was evaluated by meibum quality, expressibility, and numerical scoring. Lipid profile was done from an overnight fasting blood sample and evaluated for total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides (TGs). Results: Patients with higher stages of MGD more often had serum TGs >150 mg/dL, total cholesterol >200 mg/dL, an LDL >130 mg/dL, and serum HDL >40 mg/dL, and there exists an association between increasing stage of MGD, and age, female sex, and increasing values of all the lipid profile components. Conclusion: A very strong association exists between increasing age and increasing severity of stage of MGD. A positive association exists between female sex and increasing severity of stage of MGD. A positive association exists between increasing severity of MGD and increasing levels of all the components of lipid profiles, namely LDL, HDL, total cholesterol, and triglycerides.
Alzheimer's Disease (AD) is related to the total loss of presynaptic neurotransmitters of the cholinergic system in regions of the brain related to memory. Approximately 15% of the population beyond ...the age of 65 years are suffering from dementia due to AD and the rate is rising exponentially with age.
The objective of this research was the synthesis of a series of 1-(4-substituted-2- thioxoquinolin-1(2H)-yl)-2-substituted ethanoneV (a-c(1-4)) by undergoing acetylation at the nitrogen of 4-hydroxyquinolin-2-(1H)-one and replacing its oxygen atom with sulphur moiety via the process of thionation. To carry out-docking studies of the title compounds were carried out using Molegro Virtual Docker (MVD-2013, 6.0) software and in-vitro screening of anti-alzheimer's activity by Ellman assay method.
The synthesis of the title compounds was carried out via the sequential reaction from the initial dianilide to ring closure to the substituted quinoline-2-ones using polyphosphoric acid as a cyclising agent. These substituted quinoline-2-ones on thionation by phosphorous pentasulphide in aluminium trioxide gave quinoline-2-thiones and on further condensation with chloroacetyl chloride, they resulted in compounds with a leaving group. Nucleophilic substitution reaction of chloroacetylquinoline- 2-thiones with secondary amines resulted in the title compounds 1-(4-substituted-2- thioxoquinolin-1(2H)-yl)-2-substituted ethanone V(a-c(1-4)). The pharmacophore mapping of synthesized compounds was performed by using Molegro Virtual Docker (MVD-2013,6.0). The title compounds were tested for their in vitro anti-Alzheimer's activity using the Ellman assay method.
All the synthesized compounds were characterized by IR,
H NMR,
C NMR, and Mass spectral data. Docking studies of all the synthesized compounds were carried out using a structural mechanism for the inhibition of CDK5-p25 by roscovitine, aloisine, and indirubin (PDB ID: 1UNG), showed favourable results, with compound (Vb3) showing a MolDock score of -85.9788 that was comparable to that of the active ligand (ALH_1288 B) with MolDock score of - 87.7609.
The synthesized derivatives possessed the potential to bind with some of the amino acid residues of the active site. Compound 2-(6-chloro-4-hydroxy-2-thioxoquinolin-1(2H)-yl-1-piperazin- 1-ethanone (Vb3) was found to be the most active among the synthesized derivatives, with IC
values of 32 ± 0.1681. All the synthesized compounds showed potent to moderate activity in comparison to the reference standard donepezil.
An experimental investigation is conducted to study the mechanics of underwater implosion of cylindrical bonded sandwich composite shells. Sandwich structures comprised of concentric ...carbon-fiber/epoxy shells with PVC foam cores of different densities are imploded in a large-diameter pressure vessel. High-speed photography in conjunction with Digital Image Correlation (DIC) measurements are employed to obtain full-field displacements of the dynamic collapse process. Local dynamic pressure histories are also simultaneously recorded to investigate fluid structure interaction during implosion. Observations of collapse mode, radial displacement and velocity of collapse, interaction between the concentric shells and the foam core and post-buckling failure sequence are made. Increasing foam core shear modulus linearly increases the experimental buckling pressures. Weaker growth of incipient modal deformations are understood to play a pivotal role in obtaining higher critical buckling pressures from bonded sandwich shells than previously studied unbonded sandwich constructions. Three dynamic collapse behaviors as determined by the relative orientation of collapse between the inner and outer shell are observed. Core foam density and imperfections also strongly influence the impulse, energy and pressure pulses released from the implosions.
A series of peptide-like 25–28 membered macrocycles containing 1,3,4-oxadiazoles and pyridines bearing a chiral center scaffold have been synthesized by using known coupling reagents and common ...protecting groups. The yield of the purified macrocycles was poor on an average, yet it seems to be independent of amino acid substitution or stereochemistry. These macrocycles represent a new class of structures for further development and for future application in high-throughput screening against a variety of biological targets.
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