Autophagy is primarily considered a non‐selective degradation process induced by starvation. Nutrient‐independent basal autophagy, in contrast, imposes intracellular QC by selective disposal of ...aberrant protein aggregates and damaged organelles, a process critical for suppressing neurodegenerative diseases. The molecular mechanism that distinguishes these two fundamental autophagic responses, however, remains mysterious. Here, we identify the ubiquitin‐binding deacetylase, histone deacetylase‐6 (HDAC6), as a central component of basal autophagy that targets protein aggregates and damaged mitochondria. Surprisingly, HDAC6 is not required for autophagy activation; rather, it controls the fusion of autophagosomes to lysosomes. HDAC6 promotes autophagy by recruiting a cortactin‐dependent, actin‐remodelling machinery, which in turn assembles an F‐actin network that stimulates autophagosome–lysosome fusion and substrate degradation. Indeed, HDAC6 deficiency leads to autophagosome maturation failure, protein aggregate build‐up, and neurodegeneration. Remarkably, HDAC6 and F‐actin assembly are completely dispensable for starvation‐induced autophagy, uncovering the fundamental difference of these autophagic modes. Our study identifies HDAC6 and the actin cytoskeleton as critical components that define QC autophagy and uncovers a novel regulation of autophagy at the level of autophagosome–lysosome fusion.
This study examines the energy requirement and energy input–output relationship of colocasia-based cropping systems viz., Colocasia–onion–frenchbean, colocasia–gardenpea–frenchbean, ...colocasia–wheat–okra, colocasia–radish–potato, colocasia–cabbage–frenchbean, colocasia–coriander–cauliflower–frenchbean, colocasia–corinder–tomato and rice–wheat in the Indian Himalayas. Results revealed that potato consumed the highest total input energy (25084 MJ/ha) and the least was in coriander (5108 MJ/ha). System productivity in terms of colocasia equivalent yield was highest with colocasia–onion–frenchbean system (52.38 t/ha). Mineral fertilizers (50–62%), seed (8–26%) and irrigation water (11–17%) consumed the bulk of the input energy for all cropping systems. The total input energy was highest under colocasia–radish–potato (59919 MJ/ha) and the lowest in rice–wheat (38244 MJ/ha). Colocasia–onion–frenchbean, with the highest system productivity, produced the highest energy productivity (1.203 kg/MJ). Colocasia–coriander–tomato, with the highest system biomass, produced higher energy ratio (30.4), human energy profitability (2813.4) and energy profitability (29.43). Colocasia–wheat–okra (1362928 MJ/ha) recorded the highest total energy output. Human energy profitability was highest under colocasia–coriander–tomato (2813.4) indicating that it was the most labor energy efficient cropping system. Hence, the colocasia–corinder–tomato and colocasia–onion–frenchbean cropping systems are more suitable in the Indian Himalayas for their higher energy use efficiency and energy productivity, respectively, and are advised for wide adoption.
Abstract
Nepal is seeking carbon-free alternative fuels due to environmental concerns and economic issues resulting from fossil fuel usage. Carbon-neutral SNG has the potential as an alternative to ...LPG gas in domestic cooking, but traditional LPG equipment may not be compatible with SNG. Computational Fluid Dynamics (CFD) was used to study the compatibility of traditional LPG equipment with SNG, and it was found that essential optimization is needed to obtain optimal cooking conditions by SNG combustion. Engineering Equation Solver (EES) was used to determine the optimum inlet pressure for varying nozzle sizes. Based on the results of the study, it was determined that the optimal nozzle size for the selected type of burner is 1.15 mm. This particular nozzle size was found to provide better uniformity of flame temperature and complete combustion, resulting in an average temperature of 1700 K at a fuel inlet pressure of 2.75 kPa. This makes it a potentially better option for cooking compared to LPG, as it could potentially provide faster cooking times. The results were verified using the Python CANTERA model. A 40-50% increase in the nozzle orifice size from the traditional LPG nozzle orifice size is suggested for such conversions.
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•Novel pH sensitive surfactant-stabilized Fe3O4 nanocarriers were developed.•Nanocarriers are water-dispersible, non-toxic and protein resistant in nature.•Capable of simultaneous ...loading of hydrophilic and hydrophobic anticancer agents.•Possess potential therapeutic efficacy upon conjugated with anticancer drugs.•Nanocarriers also show excellent heating efficacy under AC magnetic field.
Highly water-dispersible surfactant-stabilized Fe3O4 magnetic nanocarriers (SMNCs) were prepared by self-assembly of anionic surfactant, sodium dodecyl sulphate (SDS) on hydrophobic (oleic acid coated) nanoparticles and their biomedical applications were investigated. These nanocarriers have an average size of about 10nm and possess tunable surface charge properties. The formation of an organic coating of SDS was evident from infrared spectroscopy, dynamic light scattering, zeta-potential and thermogravimetric measurements. These nanocarriers were used for loading of both hydrophilic and hydrophobic anticancer agents such as doxorubicin hydrochloride (DOX) and curcumin (CUR), respectively. DOX was conjugated onto the surface of nanocarriers through electrostatic interaction, whereas CUR was encapsulated into the hydrophobic interlayer between oleic acid and SDS. The toxicity and cellular internalization of drug loaded nanocarriers were investigated against WEHI-164 cancer cell line. Specifically, the drug loading, pH sensitive drug release and cellular internalization studies suggested that these nanocarriers are suitable for dual drug delivery. Furthermore, they show good heating ability under AC magnetic field, thus can be used as effective heating source for hyperthermia treatment of cancer.
We present results based on follow-up observations of the Type II-plateau supernova (II-P SN) 2013ej at six epochs spanning a total duration of ∼37 d. The R
C-band linear polarimetric observations ...were carried out between the end of the plateau and the beginning of the nebular phase, as demarcated in the photometric light-curve. The contribution arising from interstellar polarization (ISP) was constrained using two approaches, namely based on observations of foreground stars lying within a 5-arcmin and a 10
$\deg$
radius of the SN location, and by investigating the extinction arising from the Milky Way and host galaxy in the direction of the SN. Our analysis revealed that in general the intrinsic polarization of the SN was higher than the polarization values for the foreground stars and exhibited an increasing trend during our observations. After correcting for the ISP of ∼0.6 per cent,the maximum intrinsic polarization of SN 2013ej was found to be 2.14 ± 0.57 per cent. Such a strong polarization has rarely been seen in II-P SNe. If this procedure is justified (i.e. the ‘polarization bias’ effect is indeed negligible) the polarization could be caused by the asymmetry of the inner ejecta of the SN, because the ISP towards the SN location is estimated to be, at most, 0.6 per cent.
The presence of dust grains profoundly affects the diffusion of the magnetic field in molecular clouds. When the electrons and ions are well coupled to the magnetic field and charged grains are only ...indirectly coupled, emergent Hall diffusion may dominate over all the other non-ideal magnetohydrodynamic (MHD) effects in a partially ionized dusty cloud. The low-frequency, long (∼0.01-1 pc) wavelength dispersive MHD waves will propagate in such a medium with the polarization of the waves determined by the dust charge density or the dust size distribution. In the presence of shear flows, these waves may become Kelvin-Helmholtz unstable with the dust charge density or the grain size distribution operating as a switch to the instability. When Hall diffusion time is long (compared to the time over which waves are sheared), the growth rate of the instability in the presence of sub-Alfvénic flow increases with the charge number on the grain, while it is quenched in the presence of Alfvénic or super-Alfvénic flows. However, when Hall diffusion is fast, the growth rate of the instability depends on the dust charge only indirectly.
ABSTRACT
We present radio and optical afterglow observations of the TeV-bright long gamma-ray burst 190114C at a redshift of z = 0.425, which was detected by the Major Atmospheric Gamma Imaging ...Cherenkov telescope. Our observations with Atacama Large Millimeter/submillitmeter Array, Australia Telescope Compact Array, and upgraded Giant Metre-wave Radio Telescope were obtained by our low frequency observing campaign and range from ∼1 to ∼140 d after the burst and the optical observations were done with three optical telescopes spanning up to ∼25 d after the burst. Long-term radio/mm observations reveal the complex nature of the afterglow, which does not follow the spectral and temporal closure relations expected from the standard afterglow model. We find that the microphysical parameters of the external forward shock, representing the share of shock-created energy in the non-thermal electron population and magnetic field, are evolving with time. The inferred kinetic energy in the blast-wave depends strongly on the assumed ambient medium density profile, with a constant density medium demanding almost an order of magnitude higher energy than in the prompt emission, while a stellar wind-driven medium requires approximately the same amount energy as in prompt emission.
We present a multiwavelength study of the radio-loud narrow-line Seyfert 1 galaxy (NLSy1) 1H 0323+342, detected by the Fermi Gamma-Ray Space Telescope. Multiband light curves show many orphan X-ray ...and optical flares having no corresponding gamma-ray counterparts. Such anomalous variability behavior can be due to different locations of the emission region from the central source. During a large flare, a gamma-ray flux doubling timescale as small as ~3 hr is noticed. We built spectral energy distributions (SEDs) during different activity states and modeled them using a one-zone leptonic model. The shape of the optical/UV component of the SEDs is dominated by accretion disk emission in all the activity states. In the X-ray band, significant thermal emission from the hot corona is inferred during quiescent and first flaring states; however, during subsequent flares, the nonthermal jet component dominates. The gamma-ray emission in all the states can be well explained by inverse-Compton scattering of accretion disk photons reprocessed by the broad-line region. The source showed violent intra-night optical variability, coinciding with one of the high gamma-ray activity states. An analysis of the overall X-ray spectrum fitted with an absorbed power-law plus relativistic reflection component hints at the presence of an Fe Kalpha line and returns a high black hole spin value of a = 0.96 + or - 0.14. We argue that 1H 0323+342 possesses dual characteristics, akin to both flat-spectrum radio quasars (FSRQs) and radio-quiet NLSy1 galaxies, though at a low jet power regime compared to powerful FSRQs.
The recent identification of a neurodevelopmental disorder with cerebellar atrophy and motor dysfunction (NEDCAM) has resulted in an increased interest in GEMIN5, a multifunction RNA-binding protein. ...As the largest member of the survival motor neuron complex, GEMIN5 plays a key role in the biogenesis of small nuclear ribonucleoproteins while also exhibiting translational regulatory functions as an independent protein. Although many questions remain regarding both the pathogenesis and pathophysiology of this new disorder, considerable progress has been made in the brief time since its discovery. In this review, we examine GEMIN5 within the context of NEDCAM, focusing on the structure, function, and expression of the protein specifically in regard to the disorder itself. Additionally, we explore the current animal models of NEDCAM, as well as potential molecular pathways for treatment and future directions of study. This review provides a comprehensive overview of recent advances in our understanding of this unique member of the survival motor neuron complex.
•MN capped with optimum amount of OA show reduced cytotoxicity and increased SAR.•OA capped MN (MN-OA) interact mainly with the surface/membrane of the tumor cells.•MN-OA show enhanced hyperthermic ...killing ability on tumor cells.•MN-OA in combination with induction heating kill tumor cells by apoptosis.
In the present study, oleic acid (OA) functionalized Fe3O4 magnetic nanoparticles (MN) were synthesized following modified wet method of MN synthesis. The optimum amount of OA required for capping of MN and the amount of bound and unbound/free OA was determined by thermogravimetric analysis (TGA). Further, we have studied the effect of water molecules, associated with MN, on the variation in their induction heating ability under alternating current (AC) magnetic field conditions. We have employed a new approach to achieve dispersion of OA functionalized MN (MN-OA) in aqueous medium using sodium carbonate, which improves their biological applicability. Interactions amongst MN, OA and sodium carbonate were studied by Fourier transform infrared spectroscopy (FT-IR). Intracellular localization of MN-OA was studied in mouse fibrosarcoma cells (WEHI-164) by prussian blue staining and confocal laser scanning microscopy (CLSM) using nile blue A as a fluorescent probe. Results showed MN-OA to be interacting mainly with the cell membrane. Their hyperthermic killing ability was evaluated in WEHI-164 cells by trypan blue method. Cells treated with MN-OA in combination with induction heating showed decreased viability as compared to respective induction heating controls. These results were supported by altered cellular morphology after treatment of MN-OA in combination with induction heating. Further, the magnitude of apoptosis was found to be ~5 folds higher in cells treated with MN-OA in combination with induction heating as compared to untreated control. These results suggest the efficacy of MN-OA in killing of tumor cells by cellular hyperthermia.
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