Endoplasmic reticulum of all eukaryotic cells is a membrane-bound organelle. Under electron microscope it appears as parallel arrays of “rough membranes” and a maze of “smooth vesicles” respectively. ...It performs various functions in cell, i.e., synthesis of proteins to degradation of xenobiotics. Bioaccumulation of drugs/chemicals/xenobiotics in the cytosol can trigger ER stress. It is recognized by the accumulation of unfolded or misfolded proteins in the lumen of ER. Present review summarizes the present status of knowledge on ER stress caused by toxic elements, viz arsenic, cadmium, lead, mercury, copper, chromium, and nickel. While inorganic arsenic may induce various glucose-related proteins, i.e., GRP78, GRP94 and CHOP, XBP1, and calpains, cadmium upregulates GRP78. Antioxidants like ascorbic acid, NAC, and Se inhibit the expression of UPR. Exposure to lead also changes ER stress related genes, i.e., GRP 78, GRP 94, ATF4, and ATF6. Mercury too upregulates these genes. Nickel, a carcinogenic element upregulates the expression of Bak, cytochrome C, caspase-3, caspase-9, caspase-12, and GADD 153. Much is not known on ER stress caused by nanoparticles. The review describes inter-organelle association between mitochondria and ER. It also discusses the interdependence between oxidative stress and ER stress. A cross talk amongst different cellular components appears essential to disturb pathways leading to cell death. However, these molecular switches within the signaling network used by toxic elements need to be identified. Nevertheless, ER stress especially caused by toxic elements still remains to be an engaging issue.
An attempt has been made to review the endocrine/hormonal implications of a few environmentally significant metals, viz, lead, mercury, cadmium, copper, arsenic and nickel, in man and animals. ...Special emphasis has been given to the adrenals, thyroid, testis, ovary and pancreas. Toxic metals can cause structural and functional changes in the adrenal glands. Their effects on steroidogenesis have been reviewed. It has been reported that thyroid hormone kinetics are affected by a number of metallic compounds. Occupational exposure to a few of these metals can cause testicular injury and sex hormone disturbances. Protective effects of a few antioxidants on their reproductive toxicity have also been discussed. Information gathered on female reproductive toxicity of heavy metals shows that exposure to these metals can lead to disturbances in reproductive performance in exposed subjects. Certain metals can cause injury to the endocrine pancreas. Exposure to them can cause diabetes mellitus and disturb insulin homeostasis. The need to develop molecular markers of endocrine toxicity of heavy metals has been suggested. Overall information described in this review is expected to be helpful in planning future studies on endocrine toxicity of heavy metals.
ABSTRACT
We present the results of high-quality XMM-NEWTON observations of a ultraluminous X-ray source (ULX) in the galaxy NGC 4190. The detection of spectral cutoff in NGC 4190 ULX1 spectra rules ...out the interpretation of the ULX to be in a standard low/hard canonical accretion state. We report that the high quality EPIC spectra can be better described by broad thermal component, such as a slim disc. In addition we found long-term spectral and flux variability in the source using several XMM-NEWTON and Swift data. A clear anticorrelation between flux and power-law photon index is found which further confirms the unusual spectral state evolution of the ULX. Spectral properties of the ULX suggest that the source is in a broadened disc state with luminosities ≈(3 − 10) × 1039 erg s−1 falling in the ultraluminous regime. The positive luminosity–temperature relation further suggests that the multicolour disc model follows the L ∝ T4 relation that is expected for a blackbody disc emission from a constant area and the slim disc model seems to favour L ∝ T2 relation consistent with an advection-dominated disc emission. From the broadened disc-like spectral feature at such luminosity, we estimated the upper limit of the mass of the central compact object from the inner disc radius and found that the ULX hosts a stellar mass black hole.
ABSTRACT We report the detection of coherent pulsations from the ultraluminous X-ray source (ULX) NGC 7793 P13. The 0.42 s nearly sinusoidal pulsations were initially discovered in broadband X-ray ...observations using XMM-Newton and NuSTAR taken in 2016. We subsequently also found pulsations in archival XMM-Newton data taken in 2013 and 2014. The significant (>5 ) detection of coherent pulsations demonstrates that the compact object in P13 is a neutron star, and given the observed peak luminosity of 1040 erg s − 1 (assuming isotropy), it is well above the Eddington limit for a 1.4 M accretor. This makes P13 the second ULX known to be powered by an accreting neutron star. The pulse period varies between epochs, with a slow but persistent spin-up over the 2013-2016 period. This spin-up indicates a magnetic field of B 1.5 × 1012 G, typical of many Galactic accreting pulsars. The most likely explanation for the extreme luminosity is a high degree of beaming; however, this is difficult to reconcile with the sinusoidal pulse profile.
ABSTRACT We present broadband, multi-epoch X-ray spectroscopy of the pulsating ultra-luminous X-ray source (ULX) in NGC 5907. Simultaneous XMM-Newton and NuSTAR data from 2014 are best described by a ...multicolor blackbody model with a temperature gradient as a function of accretion disk radius significantly flatter than expected for a standard thin accretion disk ( , with ). Additionally, we detect a hard power-law tail at energies above 10 keV, which we interpret as being due to Comptonization. We compare this observation to archival XMM-Newton, Chandra, and NuSTAR data from 2003, 2012, and 2013, and investigate possible spectral changes as a function of phase over the 78-day super-orbital period of this source. We find that observations taken around phases 0.3-0.4 show very similar temperature profiles, even though the observed flux varies significantly, while one observation taken around phase 0 has a significantly steeper profile. We discuss these findings in light of the recent discovery that the compact object is a neutron star and show that precession of the accretion disk or the neutron star can self-consistently explain most observed phenomena.
Analysis of the chemical composition of gallstones is vital for the etiopathogenesis of gallstone diseases that can ultimately help in the prevention of its formation. In the present study, ...gallstones from seven different regions of India were analyzed to highlight the major difference in their composition. Also, gallstones of different pathological conditions i.e., benign (chronic cholecystitis, CC) and malignant gallbladder disease (gallbladder cancer GBC) were characterized. The type of polymorphs of cholesterol molecules was also studied to provide insight into the structure of gallstones. 1H solution state NMR spectroscopy 1D experiments were performed on a total of 94 gallstone (GS) samples collected from seven different geographical regions of India. Solid-State NMR spectroscopy 13C cross-polarization magic angle spinning (CPMAS) experiments were done on the 20 CC GS samples and 20 GBC GS samples of two regions. 1H NMR spectra from the solution state NMR of all the stones reveal that cholesterol was a major component of the maximum stones of the north India region while in south Indian regions, GS had very less cholesterol. 13C CPMAS experiments reveal that the quantity of cholesterol was significantly more in the GS of CC in the Lucknow region compared with GBC stones of Lucknow and Chandigarh. Our study also revealed that GS of the Lucknow region of both malignant and benign gallbladder diseases belong to the monohydrate crystalline form of cholesterol while GS of Chandigarh region of both malignant and benign gallbladder diseases exists in both monohydrate crystalline form with the amorphous type and anhydrous form. Gallstones have a complicated and poorly understood etiology. Therefore, it is important to understand the composition of gallstones, which can be found in various forms and clinical conditions. Variations in dietary practices, environmental conditions, and genetic factors may influence and contribute to the formation of GS. Prevention of gallstone formation may help in decreasing the cases of gallbladder cancer.
Health effects elicited by combined environmental exposures to xenobiotics, in many instances, still remain unresolved. One of these examples is the combined toxicity of arsenic and fluoride. The ...present study was undertaken to delineate the role of inflammation and apoptosis in hepatocellular death caused by co-exposure to arsenic and fluoride in rat. Sodium arsenate (4 mg/kg body weight) and sodium fluoride (4 mg/kg body weight) were administered to female Wistar rats, individually and in combination, for 90 days. Results on tumor necrotic factor-α (TNF-α), interleukin-12 (IL-12), and comet assay showed increased values in comparison to those obtained in arsenic- or fluoride-treated rats. Results on NO, TBARS, and caspase-9 showed higher values than fluoride-treated rats but lower levels than arsenic-treated rats. It is hypothesized that increased generation of nitric oxide induces the release of cytokines that activates caspase-9. Caspase-9 promotes the synthesis of caspase-3 that executes apoptosis. Histopathological observations on apoptotic bodies and Kupffer cells support these observations.
Graphical abstract
The hard X-ray spectrum of magnetic cataclysmic variables can be modelled to provide a measurement of white dwarf mass. This method is complementary to radial velocity measurements, which depend on ...the (typically rather uncertain) binary inclination. Here we present results from a Legacy Survey of 19 magnetic cataclysmic variables with NuSTAR.We fit accretion column models to their 20–78 keV spectra and derive the white dwarf masses, finding a weighted average M(sub WD) = 0.77 ± 0.02 M(sub ⨀), with a standard deviation σ = 0.10 M(sub ⨀), when we include the masses derived from previous NuSTAR observations of seven additional magnetic cataclysmic variables. We find that the mass distribution of accreting magnetic white dwarfs is consistent with that of white dwarfs in non-magnetic cataclysmic variables. Both peak at a higher mass than the distributions of isolated white dwarfs and post-common-envelope binaries. We speculate as to why this might be the case, proposing that consequential angular momentum losses may play a role in accreting magnetic white dwarfs and/or that our knowledge of how the white dwarf mass changes over accretion–nova cycles may also be incomplete.
Cadmium is primarily utilized in the construction of particles known as quantum dots. Hepatotoxicity caused by microparticles of cadmium is very well known; however, toxicity of nanoparticles of ...cadmium is not well understood. The present study describes the toxicity of cadmium sulfide nanoparticles (CdSNPs) in the liver of rat. Adult Wistar rats were administered CdSNPs (10 mg/kg) on alternate days for 45 days. Serum enzymes (ALT, AST, ALP), biomarkers of lipid peroxidation (MDA, H
2
O
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, and NO), and metallothionein concentration were determined. Histopathological and TEM observations were also made to record morphological changes. CdSNPs (10 mg/kg) induced significant changes in the structure and function of liver. Values of serum enzymes and reactive species increased significantly in rats treated with CdSNPs in comparison to CdS-treated rats. Histopathological observations showed extensive parenchymal degeneration. Ultrastructural studies exhibited proliferation of endoplasmic reticulum, microsomes, and lysosomes. It is concluded that NP-membrane interaction leads to the generation of reactive species that alter membrane integrity and induce oxidative stress. These events may activate cell death pathways in hepatocytes.
We present first results from a series of NuSTAR observations of the black hole X-ray binary V404 Cyg obtained during its summer 2015 outburst, primarily focusing on observations during the height of ...this outburst activity. The NuSTAR data show extreme variability in both the flux and spectral properties of the source. This is partly driven by strong and variable line-of-sight absorption, similar to previous outbursts. The latter stages of this observation are dominated by strong flares, reaching luminosities close to Eddington. During these flares, the central source appears to be relatively unobscured and the data show clear evidence for a strong contribution from relativistic reflection, providing a means to probe the geometry of the innermost accretion flow. Based on the flare properties, analogies with other Galactic black hole binaries, and also the simultaneous onset of radio activity, we argue that this intense X-ray flaring is related to transient jet activity during which the ejected plasma is the primary source of illumination for the accretion disk. If this is the case, then our reflection modeling implies that these jets are launched in close proximity to the black hole (as close as a few gravitational radii), consistent with expectations for jet launching models that tap either the spin of the central black hole, or the very innermost accretion disk. Our analysis also allows us to place the first constraints on the black hole spin for this source, which we find to be (99% statistical uncertainty, based on an idealized lamp-post geometry).
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